BCMA car-t compositions and uses thereof

Abstract

Compositions and methods described herein relate to chimeric antigen receptors (CARs) targeting B cell maturation antigen (BCMA) and uses thereof in therapy. Engineered T cells comprising an anti-BCMA CAR are also provided. The engineered cells may comprise a genetic modification in one or more of the HLA-A, HLA-B, TRAC, CIITA, or TGFBR2 genes.

Description

BCMA CAR-T COMPOSITIONS AND USES THEREOF CROSS REERENCE TO RELATED APPLICATIONS

[0001] This application claims priority to U.S. Provisional Application No. 63 / 760,997, filed on February 20, 2025, and U.S. Provisional Application No. 63,974,415, filed on February 2, 2026, both of which are incorporated herein by reference in their entirety.SEQUENCE LISTING

[0002] The instant application contains a Sequence Listing which has been submitted in xml format and is hereby incorporated by reference in its entirety. Said xml copy, created on February 19, 2026, is named “I121468_1090WO_SL” and is 3,304,894 bytes in size.INTRODUCTION

[0003] The present disclosure generally describes chimeric antigen receptor (CAR) reagents (e.g., cells and compositions) and methods. The present disclosure relates to use of CAR technology in conjunction with CRISPR systems for providing CAR-transduced immune effector cells (e.g., T-cells, NK cells).

[0004] B cell maturation antigen (BCMA) is a transmembrane receptor protein that is preferentially expressed on the surface of mature B lymphocytes and can bind to B-cell activating factor (BAFF). BCMA is a member of the tumor necrosis factor (TNF) receptor superfamily, and is also referred to as TNFRSF17. BCMA is highly expressed on myeloma cell surfaces.

[0005] Despite its therapeutic promise, anti-BCMA CAR-T therapy presents many logistical and technical hurdles. Current protocols for CAR-T are based on autologous cell transfer. In this approach, T-cells recovered from a patient are genetically modified ex vivo and cultivated in vitro before being infused into the patient. This approach, which uses the patient’s own lymphocytes, reduces the risk of rejection. However, so-called autologous therapies are predicated on the availability of functional lymphocytes, which may be compromised by prior lines of treatment. Moreover, each patient’s autologous cell preparation is effectively a new product, resulting in substantial variation in safety and efficacy.

[0006] “Off the shelf’ therapies using donor (allogeneic) cells obviate the need to recover and modify the patient’s own lymphocytes. However, allogeneic CAR-T cells may provoke an undesirable immune response or otherwise be short-lived. Often, immune rejection of allogeneic cells results from a mismatching of major histocompatibility complex (MHC)molecules between the donor and recipient. Slight differences, e.g., in MHC alleles between individuals can cause the T-cells in a recipient to become activated. During T-cell development, an individual’s T-cell repertoire is tolerized to one’s own MHC molecules, but T-cells that recognize another individual’s MHC molecules may persist in circulation and are referred to as alloreactive T-cells. Alloreactive T-cells can become activated e.g., by the presence of another individual’s cells expressing MHC molecules in the body, causing e.g., graft versus host disease and transplant rejection.

[0007] Methods and compositions for reducing the susceptibility of an allogeneic anti-BCMA CAR-T cell to rejection, or for improving the activity of an anti-BCMA CAR-T cell, are of interest.SUMMARY

[0008] Thus, there exists a need for improved methods and compositions for modifying anti-BCMA CAR-T cells to overcome the problem of recipient immune rejection, and to improve the activity of anti-BCMA CAR-T cells as a therapeutic.

[0009] In some embodiments, an anti-BCMA CAR-T cell described herein comprises an anti-B cell maturation antigen (BCMA) chimeric antigen receptor (CAR) comprising an antigen-binding domain that specifically binds to BCMA, wherein the antigen-binding domain comprises a monospecific, bivalent VHH comprising a first heavy chain variable (VH) region and a second VH region each comprising a complementarity determining region 1 (VH CDR1), a VH CDR2, and VH CDR3 as set forth in the amino acid sequences of SEQ ID NO: 63, SEQ ID NO: 65, and SEQ ID NO: 67, respectively, a transmembrane domain; and an intracellular domain (ICD) comprising a costimulatory domain, e.g., a costimulatory domain comprising an amino acid sequence of SEQ ID NO: 71.

[0010] In certain embodiments, the first and / or the second VH region of the anti-BCMA CAR each comprises an amino acid sequence having at least 90%, 93%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO: 81. In other embodiments, the first and / or the second VH region of the anti-BCMA CAR each comprises the amino acid sequence of SEQ ID NO: 81. In some embodiments, the first VH region comprises the amino acid sequence of SEQ ID NO: 81, and the second VH region comprises the amino acid sequence of SEQ ID NO: 81.

[0011] In some embodiments, the bivalent VHH of the anti-BCMA CAR provided herein comprises a linker between the first and second VH regions. In one embodiment, the linker is a glycine-serine linker, e.g., the glycine-serine linker set forth in the sequence of SEQ ID NO: 73.

[0012] In one embodiment, the antigen-binding domain of the anti-BCMA CAR comprises the amino acid sequence of SEQ ID NO: 84.

[0013] In another embodiment, the transmembrane domain of the anti-BCMA CAR comprises a CD8a transmembrane domain comprising an amino acid sequence of SEQ ID NO: 70. In certain embodiments, the anti-BCMA CAR further comprises a hinge domain between the antigen-binding domain and the transmembrane domain, optionally wherein the hinge domain is a CD8a hinge domain, or fragment thereof, comprising an amino acid sequence of SEQ ID NO: 69.

[0014] In yet other embodiments, the intracellular domain of the anti-BCMA CAR further comprises an activation domain, optionally wherein the activation domain is a CD3z activation domain comprising an amino acid sequence of SEQ ID NO: 72.

[0015] In one embodiment, the anti-BCMA CAR described herein comprises an amino acid sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 83. In one embodiment, the anti-BCMA CAR described herein comprises an amino acid sequence as set forth in SEQ ID NO: 83.

[0016] In other embodiments, the anti-BCMA CAR comprises an antigen-binding domain comprising a means for binding to BCMA.

[0017] In certain embodiments, the first VH region of the antigen-binding portion of the anti-BCMA CAR is encoded by a nucleic acid sequence having at least 90%, 93%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO: 80 and the second VH region is encoded by a nucleic acid sequence having at least 90%, 93%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO: 80.

[0018] In yet another embodiment, the anti-BCMA CAR provided herein is encoded by a nucleic acid sequence that is at least 95% identical to the nucleic acid sequence of SEQ ID NO: 82.

[0019] Also provided is a nucleic acid encoding an anti-BCMA CAR described herein. In one embodiment, the nucleic acid comprises a nucleic acid sequence of SEQ ID NO: 82, or a nucleic acid sequence that has at least 90%, 93%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO: 82.

[0020] The disclosure further includes an mRNA encoding a nucleic acid described herein.

[0021] Also provided is an expression vector operably linked to or comprising a nucleic acid disclosed herein.

[0022] Provided herein is an engineered cell comprising a nucleic acid, an mRNA, or an expression vector disclosed herein.

[0023] Also provided herein is an engineered cell comprising an anti-BCMA CAR as disclosed herein, optionally wherein the cell is transduced with an expression vector operably linked to or comprising a nucleic acid encoding the anti-BCMA CAR, and optionally wherein the expression vector directs expression of the anti-BCMA CAR in the cell. In certain embodiments, the expression vector comprises a retroviral or lentiviral expression vector. In other embodiments, the expression vector comprises an AAV vector.

[0024] Provided herein is an engineered cell comprising an anti-BCMA CAR, wherein the anti-BCMA CAR comprises an antigen-binding domain that specifically binds to BCMA, wherein the antigen-binding domain comprises a monospecific, bivalent VHH comprising a first VH region and a second VH region each comprising a VH CDR1, a VH CDR2, and VH CDR3 as set forth in the amino acid sequences of SEQ ID NO: 63, SEQ ID NO: 65, and SEQ ID NO: 67, respectively, a transmembrane domain; and an intracellular domain comprising a costimulatory domain comprising an amino acid sequence of SEQ ID NO: 71. In one embodiment, the first and / or the second VH region each comprise an amino acid sequence having at least 90%, 93%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO: 81, or wherein the first and / or the second VH region comprise the amino acid sequence of SEQ ID NO: 81. In another embodiment, the first VH region comprises the amino acid sequence of SEQ ID NO: 81, and the second VH region comprises the amino acid sequence of SEQ ID NO: 81. In another embodiment, the antigen-binding domain comprises the amino acid sequence of SEQ ID NO: 84. In certain embodiments, the bivalent VHH comprises a linker between the first and second VH regions. In certain other embodiments, the linker is a glycine-serine linker, e.g., the glycine-serine linker comprises the sequence of SEQ ID NO: 73. In still other embodiments, the transmembrane domain comprises a CD8a transmembrane (TM) domain comprising an amino acid sequence of SEQ ID NO: 70; optionally, further comprising a hinge domain between the antigen-binding domain and the transmembrane domain, optionally wherein the hinge domain is a CD8a hinge domain, or fragment thereof, comprising an amino acid sequence of SEQ ID NO: 69. In one embodiment, the intracellular domain further comprises an activation domain, optionally wherein the activation domain is a CD3z activation domain comprising an amino acid sequence of SEQ ID NO: 72.

[0025] Also provided herein is an engineered cell comprising an anti-BCMA CAR, wherein the anti-BCMA CAR comprises an amino acid sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 83, or wherein the anti-BCMA CAR comprises the amino acid sequence of SEQ ID NO: 83.

[0026] In other embodiments, provided is an engineered cell comprising an anti-BCMA CAR comprising an antigen-binding domain comprising a means for binding to BCMA.

[0027] Further disclosed is a population of cells comprising an engineered cell as set forth herein.

[0028] The engineered cell expressing an anti-BCMA CAR as described herein, also comprises a genetic modification in the HLA-A, HLA-B, TRAC, or CIITA (class II major histocompatibility complex transactivator) locus, which may be useful in cell therapy. In certain further embodiments, the engineered cell comprises a genetic modification in TGFBR2. The disclosure further provides compositions and methods to reduce or eliminate surface expression of endogenous T-cell receptor, MHC class I or II protein, or TGFBR2 in a cell by genetically modifying the HLA-A, HLA-B, TRAC, or CIITA, locus, e.g., by genomic editing of anti-BCMA CAR-T cells by CRISPR / Cas9 systems. In further embodiments, TGBFR2 is genetically modified in an engineered cell disclosed herein, e.g., by genomic editing of an anti-CAR-T cell by CRISPR / Cas9 system.

[0029] Provided is an engineered cell or population of cells as described herein, comprising reduced or eliminated surface expression of HLA-A relative to an unmodified cell.

[0030] In one embodiment, the engineered cell or population of cells as described herein, comprises a genetic modification in the HLA-A gene, optionally wherein the genetic modification comprises at least one nucleotide within the genomic coordinates: (a) chr6:29942854-29942913 and chr6:29943518-29943619; and (b) chr6:29942540-29945459. In one embodiment, the genetic modification is within the genomic coordinates chosen from chr6:29942891-29942915; and chr6:29942609-29942633, and optionally wherein the genetic modification comprises at least one nucleotide within the genomic coordinates targeted by an HLA-A guide RNA comprising a guide sequence of SEQ ID NO: 403.

[0031] Further disclosed is an engineered cell or population of cells as described herein, which has reduced or eliminated surface expression of HLA-B relative to an unmodified cell.

[0032] In one embodiment, the engineered cell or population of cells as described herein comprises a genetic modification in the HLA-B gene, optionally wherein the genetic modification is within the genomic coordinates chosen from (a) chr6:31354480-31357174 and (b) chr6:31357084-31354647. In one embodiment, the genetic modification is within the genomic coordinates chosen from chr6:31355222-31355246, chr6:31355221-31355245, and chr6:31355205-31355229, optionally wherein the genetic modification comprises at least one nucleotide within the genomic coordinates targeted by an HLA-B guide RNA comprising a guide sequence of SEQ ID NO: 406.

[0033] Disclosed is an engineered cell or population of cells described herein, which has reduced or eliminated surface expression of TRAC relative to an unmodified cell.

[0034] In one embodiment, the reduced or eliminated surface expression of TRAC on the engineered cell or population of cells is by genetically modifying the TRAC gene. In one embodiment, the gene modification comprises at least one nucleotide within the genomic coordinates chr14:22547524- 22547544, optionally wherein the genetic modification comprises at least one nucleotide within the genomic coordinates targeted by a TRAC guide RNA comprising a guide sequence of SEQ ID NO: 413.

[0035] Disclosed is an engineered cell or population of cells described herein, which has reduced or eliminated surface expression of MHC class II relative to an unmodified cell.

[0036] In one embodiment, the reduced or eliminated surface expression of MHC class II is by genetically modifying the CIITA gene, optionally wherein the genetic modification is within the genetic coordinates chosen from: (a) chr16:10877363-10907788 and (b) chr16:10906515-10908136. In one embodiment, the genetic modification comprises at least one nucleotide within the genomic coordinates chr16: 10906643-10906667 orchrl6: 10907504-10907528, optionally wherein the genetic modification comprises at least one nucleotide within the genomic coordinates targeted by a CIITA guide RNA comprising a guide sequence of SEQ ID NO: 402.

[0037] In one embodiment, the engineered cell or population of cells disclosed herein has reduced or eliminated surface expression of endogenous T-cell receptor, MHC class I and II protein, by genetically modifying the HLA-A, HLA-B, TRAC, and / or CIITA locus. In certain further embodiments, the engineered cell or population of cells disclosed herein has reduced or eliminated surface expression of TGFBR2 protein, by genetically modifying the TGFBR2 locus.

[0038] In a further embodiment, the engineered cell or population of cells disclosed herein has reduced or eliminated surface expression of TGFBR2 relative to an unmodified cell.

[0039] In one embodiment, reduced or eliminated surface expression of TGFBR2 is by genetically modifying the TGFBR2 gene, optionally wherein the genetic modification comprises at least one nucleotide within the genomic coordinates: chr3:30606864-30691614. In one embodiment, the genetic modification is within the genomic coordinates chr3:30674205-30674229, optionally wherein the genetic modification comprises at least one nucleotide within the genomic coordinates targeted by a TGFBR2 guide RNA comprising a guide sequence of SEQ ID NO: 301. In another embodiment, the genetic modification is within the genomic coordinates chr3: 30671941-30671961, optionally wherein the geneticmodification comprises at least one nucleotide within the genomic coordinates targeted by a TGFBR2 guide RNA comprising a guide sequence of SEQ ID NO: 302.

[0040] In certain embodiments, the genetic modification of the engineered cell or population of cells comprises an indel, a C to T substitution, or an A to G substitution within the genomic coordinates. In another embodiment, the genetic modification comprises an insertion of a heterologous coding sequence.

[0041] Provided is an engineered cell comprising a genetic modification in the HLA-A gene, a modified TRAC gene, and / or a genetic modification in the CIITA gene, wherein the engineered cell expresses an anti-BCMA chimeric antigen receptor (CAR) or comprises a nucleic acid encoding an anti-BCMA CAR. In a further embodiment, the engineered cell further comprises a genetic modification in the TGFBR2 gene.

[0042] Also provided is an engineered cell comprising a genetic modification in the HLA-A gene, a genetic modification in the HLA-B gene, a genetic modification in the TRAC gene, and / or a genetic modification in the CIITA gene, wherein the engineered cell expresses an anti-BCMA chimeric antigen receptor (CAR) or comprises a nucleic acid encoding an anti-BCMA CAR. In a further embodiment, the engineered cell comprises a genetic modification in the TGFBR2 gene.

[0043] In certain embodiments, an engineered cell or a population of cells disclosed herein is homozygous for HLA-C, optionally wherein the cell is homozygous for HLA-B and HLA-C.

[0044] Provided is a pharmaceutical composition comprising an engineered cell or a population of cells disclosed herein.

[0045] In certain embodiments, an engineered cell disclosed herein comprises a genome comprising a nucleic acid of SEQ ID NO: 107. Further contemplated is a population of such cells, and a composition comprising said engineered cell or a population thereof.

[0046] In certain embodiments, the engineered cell, including cells in a population or a pharmaceutical composition, is an immune cell.

[0047] In one embodiment, the engineered cell, including cells in a population or a pharmaceutical composition, is an NK cell.

[0048] In another embodiment, the engineered cell, including cells in a population or a pharmaceutical composition, is a T-cell, optionally wherein the T-cell is a CD4+ T-cell, optionally wherein the T-cell is a CD8+ T-cell, or optionally wherein the T-cell has a T memory stem cell (Tscm) phenotype.

[0049] An engineered cell disclosed herein, including a population of engineered cells or a pharmaceutical composition comprising said cells, is engineered with a genomic editing system. In one embodiment, the genomic editing system comprises an RNA-guided DNA-binding agent or a nucleic acid encoding an RNA-guided DNA-binding agent, optionally wherein the RNA-guided DNA-binding agent or the RNA-guided DNA-binding agent encoded by the nucleic acid is S. pyogenes Cas9 (SpyCas9), or optionally wherein the RNA-guided DNA-binding agent or the RNA-guided DNA-binding agent encoded by the nucleic acid is N. meningitidis Cas9 (NmeCas9).

[0050] In one embodiment, the guide RNA is provided to the cell in a vector, and / or wherein the RNA-guided DNA-binding agent is provided to the cell in a vector, optionally in the same vector as the guide RNA.

[0051] In certain embodiments, the nucleic acid encoding the anti-BCMA CAR is provided to the engineered cell in an expression vector. In one embodiment, the expression vector is a viral vector, optionally wherein the expression vector comprises an AAV vector, and optionally wherein the expression vector comprises SEQ ID NO: 106. In another embodiment, the expression vector is a non-viral vector. In certain embodiments, the guide RNA is provided to the cell in a lipid nanoparticle (LNP), optionally in the same LNP an RNA-guided DNA-binding agent is provided. In one embodiment, the nucleic acid encoding the anti-BCMA CAR is provided to the cell in a lipid nanoparticle (LNP).

[0052] In some embodiments, a method of reducing surface expression of HLA-A protein in an engineered cell relative to an unmodified cell, is provided, the method comprising contacting a cell with a composition of any of embodiments provided herein. In some embodiments, a method of reducing surface expression of HLA-B protein in an engineered cell relative to an unmodified cell, is provided, the method comprising contacting a cell with a composition of any of embodiments provided herein. In some embodiments, a method of reducing surface expression of TRAC protein in an engineered cell relative to an unmodified cell, is provided, the method comprising contacting a cell with a composition of any of embodiments provided herein. In some embodiments, a method of reducing surface expression of MHC class II protein (e.g., by reducing expression of CIITA) in an engineered cell relative to an unmodified cell, is provided, the method comprising contacting a cell with a composition of any of embodiments provided herein. In some embodiments, a method of reducing surface expression of TGFBR2 protein in an engineered cell relative to an unmodified cell, is provided, the method comprising contacting a cell with a composition of any of embodiments provided herein.

[0053] In one embodiment, provided is a method of making an engineered cell comprising contacting a cell with a nucleic acid disclosed herein, or an mRNA disclosed herein, or an expression vector disclosed herein, and at least one genomic editing tool comprising an RNA-guided DNA-binding agent and at least one guide RNA, wherein the at least one guide RNA targets a genomic locus chosen from the HLA-A, HLA-B, TRAC, CIITA, and / or TGFBR2 locus.

[0054] In one embodiment, provided is a method of making an engineered cell comprising an anti-BCMA CAR comprising providing an engineered cell which has reduced or eliminated surface expression of one or more of HLA-A, HLA-B, MHC Class II, and TRAC, and optionally wherein the cell has reduced or eliminated surface expression of TGFBR2, relative to an unmodified cell; and contacting the cell with a nucleic acid disclosed herein, or an mRNA disclosed herein, or an expression vector disclosed herein.

[0055] Also provided is a method of making an engineered cell comprising an anti-BCMA CAR, comprising: (a) contacting the cell with a first lipid nanoparticle (LNP) comprising a base editor and a guide RNA that targets HLA-A, (b) contacting the cell with a second LNP comprising a base editor and a guide RNA that targets HLA-B, (c) contacting the cell with a third LNP comprising a base editor and a guide RNA that targets CIITA, (d) optionally contacting the cell with a fourth LNP comprising a base editor and a guide RNA that targets TGFBR2, (e) contacting the cell with a fifth LNP comprising an mRNA encoding UGI, (f) contacting the cell with a sixth LNP comprising an RNA-guided cleavase and at least one gRNA that is cognate to the RNA-guided cleavase and targets the TRAC locus; and (g) contacting the cell with a nucleic acid encoding an anti-BCMA CAR for insertion into an editing site (e.g., a double strand break) at the TRAC locus. In one embodiment, the RNA-guided cleavase comprises an S. pyogenes (Spy) Cas9 cleavase, and the base editor comprises an N. meningitidis (Nme) Cas9 nickase.

[0056] Disclosed is a method of making an engineered cell comprising an anti-BCMA CAR, comprising: (a) contacting a cell with a first population of lipid nanoparticles (LNPs) comprising a first LNP comprising a base editor and a gRNA that targets the HLA-B locus; optionally a second LNP comprising a base editor and a gRNA that targets the TGFBR2 locus, and a third LNP comprising a uracil glycosylase inhibitor (UGI); (b) contacting a cell with (i) a second population of LNPs comprising a fourth LNP comprising a base editor and a gRNA that targets the HLA-A locus; a fifth LNP comprising a base editor and a gRNA that targets the CIITA locus; a sixth LNP comprising an RNA-guided DNA cleavase and a gRNA that is cognate to the RNA-guide DNA cleavase and targets the TRAC locus, and (ii) anucleic acid encoding an anti-BCMA CAR for insertion into an editing site (e.g., a double strand break) at the TRAC locus. In one embodiment, the RNA-guided cleavase comprises an S. pyogenes (Spy) Cas9 cleavase, and the base editor comprises an N. meningitidis (Nme) Cas9 nickase.

[0057] Further disclosed is a viral vector comprising the nucleic acid sequence of SEQ ID NO: 106.

[0058] Also provided is a method of administering an engineered cell, population of cells, or pharmaceutical composition disclosed herein to a subject in need thereof, or to a subject as an adoptive cell transfer (ACT) therapy.

[0059] Disclosed is also a method of treating a disease or disorder, comprising administering the engineered cell, population of cells, or pharmaceutical composition disclosed herein to a subject in need thereof. In one embodiment, the engineered cell is allogeneic to the subject.

[0060] In one embodiment, provided is an engineered cell, population of cells, composition, or method disclosed herein, for use in administration to a subject as an adoptive cell transfer (ACT) therapy, for use in treating a subject having a cancer, for use in treating a subject having an infectious disease, or for use in treating a subject having an autoimmune disease.

[0061] In one embodiment, the engineered cell, population of cells, composition, or method disclosed herein is for use in reducing tumor growth in a subject having a cancer. In one embodiment, the tumor is a myeloma tumor. In one embodiment, the volume of at least one myeloma tumor cell is reduced.

[0062] Also disclosed is the use of an engineered cell, population of cells, or composition disclosed herein for the manufacture of a medicament for the treatment of a subject having a cancer, an infectious disease, or an autoimmune disease.

[0063] Provided is an engineered cell comprising a genetic modification in the HLA-A gene, a genetic modification in the HLA-B gene, a genetic modification in the TRAC gene, and / or a genetic modification in the CIITA gene, wherein the genetic modification in the HLA-A gene is within the genomic coordinates chr6:29942891-29942915; wherein the genetic modification in the HLA-B gene is within the genomic coordinates chr6:31355222-31355246, chr6:31355221-31355245, or chr6:31355205-31355229; wherein the genetic modification in the TRAC gene is within the genomic coordinates chr14: 22547524-22547544; and wherein the genetic modification in the CIITA gene is within the genomic coordinates chr16:10907504-10907528 or chr16:10906643-10906667; wherein theengineered cell comprises an anti-BCMA chimeric antigen receptor (CAR) or comprises a nucleic acid encoding an anti-BCMA CAR. In one embodiment, the engineered cell further comprises a genetic modification in the TGFBR2 gene, wherein the genetic modification in the TGFBR2 gene is within the genomic coordinates chr3:30674205-30674229 or chr3:30671941-30671961.

[0064] Also provided is an engineered cell comprising a genetic modification in the HLA-A gene, a genetic modification in the HLA-B gene, a genetic modification in the TRAC gene, and / or a genetic modification in the CIITA gene, wherein the genetic modification in the HLA-A gene is within the genomic coordinates chr6:29942891-29942915; wherein the genetic modification in the HLA-B gene is within the genomic coordinates chr6:31355222-31355246; wherein the genetic modification in the TRAC gene is within the genomic coordinates chr14:22547524-22547544; and wherein the genetic modification in the CIITA gene is within the genomic coordinates chr16: 10906643-10906667; wherein the engineered cell comprises an anti-BCMA chimeric antigen receptor (CAR) or comprises a nucleic acid encoding an anti-BCMA CAR. In one embodiment, the engineered cell further comprises a genetic modification in the TGFBR2 gene, wherein the genetic modification in the TGFBR2 gene is within the genomic coordinates chr3:30674205-30674229.

[0065] Also provided is an engineered human T cell comprising multiple genetic modifications and an anti-BCMA CAR, wherein (a) the engineered human T cell comprises a genetic modification in the HLA-A gene and reduced or eliminated surface expression of HLA-A relative to an unmodified cell, a genetic modification in the HLA-B gene and reduced or eliminated surface expression of HLA-B relative to an unmodified cell, a genetic modification in the CIITA gene and reduced or eliminated surface expression of MHC class II relative to an unmodified cell, optionally a genetic modification in the TGFBR2 gene and reduced or eliminated surface expression of TGFBR2 relative to an unmodified cell, and (b) the anti-BCMA CAR comprises an antigen-binding domain that binds to BCMA, wherein the antigen-binding domain comprises a monospecific, bivalent VHH comprising a first heavy chain variable (VH) region and a second VH region each comprising a VH CDR1, a VH CDR2, and VH CDR3 as set forth in the amino acid sequences of SEQ ID NO: 63, SEQ ID NO: 65, and SEQ ID NO: 67, respectively, wherein the anti-BCMA CAR is inserted into the TRAC locus.

[0066] Disclosed is an engineered human T cell comprising multiple genetic modifications and an anti-BCMA CAR, wherein (a) the engineered human T cell comprises a genetic modification in the HLA-A gene within the genomic coordinates chr6:29942891-29942915, agenetic modification in the HLA-B gene within the genomic coordinates chr6:31355222-31355246, a genetic modification in the CIITA gene within the genomic coordinates chr16: 10906643-10906667, optionally a genetic modification in the TGFBR2 gene within the genomic coordinates chr3:30674205-30674229, and (b) the anti-BCMA CAR comprises an antigen-binding domain that binds to BCMA, wherein the antigen-binding domain comprises a monospecific, bivalent VHH comprising a first VH region and a second VH region each comprising a VH CDR1, a VH CDR2, and VH CDR3 as set forth in the amino acid sequences of SEQ ID NO: 63, SEQ ID NO: 65, and SEQ ID NO: 67, respectively, wherein the anti-BCMA CAR is inserted into the TRAC locus.

[0067] Further disclosed is an engineered human T cell comprising multiple genetic modifications and an anti-BCMA CAR, wherein (a) the engineered human T cell comprises a genetic modification in the HLA-A gene within the genomic coordinates chr6:29942891-29942915, a genetic modification in the HLA-B gene within the genomic coordinates chr6:31355222-31355246, a genetic modification in the CIITA gene within the genomic coordinates chr16: 10906643-10906667, and optionally a genetic modification in the TGFBR2 gene within the genomic coordinates chr3:30674205-30674229, and (b) the anti-BCMA CAR comprises an antigen-binding domain that binds to BCMA, wherein the antigen-binding domain comprises a monospecific, bivalent VHH comprising a first VH region and a second VH region each comprising a VH CDR1, a VH CDR2, and VH CDR3 as set forth in the amino acid sequences of SEQ ID NO: 63, SEQ ID NO: 65, and SEQ ID NO: 67, respectively, wherein the anti-BCMA CAR is inserted into the TRAC locus within the genomic coordinates chr14:22547524-22547544.

[0068] In one the first and the second VH region each comprises the amino acid sequence of SEQ ID NO: 81.

[0069] In another embodiment, the anti-BCMA CAR comprises the amino acid sequence of SEQ ID NO: 83.

[0070] In yet another embodiment, the engineered human T cell is a CD4+ or CD8+ T cell.

[0071] In still another embodiment, the engineered human T cell is homozygous for HLA-C, optionally wherein the engineered human T cell is homozygous for HLA-B and for HLA-C.

[0072] Also disclosed is a pharmaceutical composition comprising a population of T cells, wherein the population of T cells comprises CD4+ T cells and / or CD8+ T cells, which comprise an engineered human T cell comprising multiple genetic modifications and an anti-BCMA chimeric antigen receptor (CAR), wherein (a) the engineered human T cell comprisesa genetic modification in the HLA-A gene and reduced or eliminated surface expression of HLA-A relative to an unmodified cell, a genetic modification in the HLA-B gene and reduced or eliminated surface expression of HLA-B relative to an unmodified cell, a genetic modification in the CIITA gene and reduced or eliminated surface expression of MHC class II relative to an unmodified cell, optionally a genetic modification in the TGFBR2 gene and reduced or eliminated surface expression of TGFBR2 relative to an unmodified cell, and (b) the anti-BCMA CAR comprises an antigen-binding domain that binds to BCMA, wherein the antigen-binding domain comprises a monospecific, bivalent VHH comprising a first VH region and a second VH region each comprising a VH CDR1, a VH CDR2, and VH CDR3 as set forth in the amino acid sequences of SEQ ID NO: 63, SEQ ID NO: 65, and SEQ ID NO: 67, respectively, wherein the anti-BCMA CAR is inserted into the TRAC locus.

[0073] Provided as well is a pharmaceutical composition comprising a population of T cells, wherein the population of T cells comprises CD4+ T cells and / or CD8+ T cells, which comprise an engineered human T cell comprising multiple genetic modifications and an anti-BCMA CAR, wherein (a) the engineered human T cell comprises a genetic modification in the HLA-A gene within the genomic coordinates chr6:29942891-29942915, a genetic modification in the HLA-B gene within the genomic coordinates chr6:31355222-31355246, a genetic modification in the CIITA gene within the genomic coordinates chr16: 10906643-10906667, optionally a genetic modification in the TGFBR2 gene within the genomic coordinates chr3:30674205-30674229, and (b) the anti-BCMA CAR comprises an antigenbinding domain that binds to BCMA, wherein the antigen-binding domain comprises a monospecific, bivalent VHH comprising a first VH region and a second VH region each comprising a VH CDR1, a VH CDR2, and VH CDR3 as set forth in the amino acid sequences of SEQ ID NO: 63, SEQ ID NO: 65, and SEQ ID NO: 67, respectively, wherein the anti-BCMA CAR is inserted into the TRAC locus.

[0074] Also disclosed is a pharmaceutical composition comprising a population of T cells, wherein the population of T cells comprises CD4+ T cells and / or CD8+ T cells, which comprise an engineered human T cell comprising multiple genetic modifications and an anti-BCMA CAR, wherein (a) the engineered human T cell comprises a genetic modification in the HLA-A gene within the genomic coordinates chr6:29942891-29942915, a genetic modification in the HLA-B gene within the genomic coordinates chr6:31355222-31355246, a genetic modification in the CIITA gene within the genomic coordinates chr16: 10906643-10906667, optionally a genetic modification in the TGFBR2 gene within the genomic coordinates chr3:30674205-30674229, and (b) the anti-BCMA CAR comprises an antigen-binding domain that binds to BCMA, wherein the antigen-binding domain comprises a monospecific, bivalent VHH comprising a first VH region and a second VH region each comprising a VH CDR1, a VH CDR2, and VH CDR3 as set forth in the amino acid sequences of SEQ ID NO: 63, SEQ ID NO: 65, and SEQ ID NO: 67, respectively, wherein the anti-BCMA CAR is inserted into the TRAC locus within the genomic coordinates chr14:22547524-22547544.

[0075] In one embodiment, the first and the second VH region each comprises the amino acid sequence of SEQ ID NO: 81.

[0076] In another embodiment, the anti-BCMA CAR comprises the amino acid sequence of SEQ ID NO: 83.

[0077] In a further embodiment, the engineered human T cell is homozygous for HLA-C; optionally wherein the engineered human T cell is homozygous for HLA-B and for HLA-C.

[0078] Further disclosed is a method of administering the engineered human T cell or pharmaceutical composition provided herein to a subject in need thereof, or to a subject as an adoptive cell transfer (ACT) therapy.

[0079] Provided is a method of treating a disease or disorder, comprising administering the engineered human T cell or pharmaceutical composition disclosed herein to a subject in need thereof.

[0080] In one embodiment, the engineered human T cell or pharmaceutical composition disclosed herein is for use in administration to a subject as an adoptive cell transfer (ACT) therapy, for use in treating a subject having a cancer, or for use in treating a subject having an autoimmune disease. In one embodiment, the disease or disorder is a cancer, e.g., a solid tumor or a hematological malignancy, e.g., multiple myeloma. In one embodiment, the disease or disorder is an autoimmune disease.

[0081] In one embodiment, the engineered human T cell or pharmaceutical composition disclosed herein is for use in reducing growth of a tumor, e.g., a myeloma tumor. In one embodiment, the volume of at least one multiple myeloma tumor is reduced.

[0082] In one embodiment, the disease or disorder is a B cell or plasma cell autoimmune disease, such as myasthenia gravis (MG), systemic lupus erythematosus (SLE), and neuromyelitis optica spectrum disorder (NMOSD), idiopathic inflammatory myopathy (IIM), multiple sclerosis (MS), primary Sjogren's syndrome (PSS), or stiff person syndrome (SPS).

[0083] Further disclosed is a method of treatment, comprising administering to an individual in need thereof, an effective dose of an engineered cell comprising an anti-BCMA CAR disclosed herein, or a pharmaceutical composition described herein.

[0084] In addition, provided is use of an engineered cell comprising an anti-BCMA CAR as disclosed herein in the preparation of a medicament for the treatment of a disease or disorder of an individual in need.

[0085] Also provided is an engineered cell comprising an anti-BCMA CAR disclosed herein or a pharmaceutical composition disclosed herein, for use in therapy in an individual in need.

[0086] In some aspects, provided herein is a messenger RNA (mRNA) encoding an anti-B cell maturation antigen (BCMA) chimeric antigen receptor (CAR), wherein the anti-BCMA CAR comprises: a) an antigen-binding domain that specifically binds to BCMA, wherein the antigen-binding domain comprises a monospecific, bivalent VHHcomprising a first heavy chain variable (VH) region and a second VH region each comprising a complementarity determining region 1 (VH CDR1), a VH CDR2, and VH CDR3 as set forth in the amino acid sequences of SEQ ID NO: 63, SEQ ID NO: 65, and SEQ ID NO: 67, respectively; b) a transmembrane domain; and c) an intracellular domain (ICD) comprising a costimulatory domain comprising an amino acid sequence of SEQ ID NO: 71. In some embodiments, the first and / or the second VH region each comprise an amino acid sequence having at least 90%, 93%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO: 81, or the first and / or the second VH region each comprises the amino acid sequence of SEQ ID NO: 81. In some embodiments, the first VH region comprises the amino acid sequence of SEQ ID NO: 81, and the second VH region comprises the amino acid sequence of SEQ ID NO: 81. In some embodiments, the bivalent VHH comprises a linker between the first and second VH regions. In some embodiments, the linker is a glycine-serine linker, e.g., a glycine-serine linker comprising the sequence of SEQ ID NO: 73. In some embodiments, the antigenbinding domain comprises the amino acid sequence of SEQ ID NO: 84. In some embodiments, the transmembrane domain comprises a CD8a transmembrane domain comprising an amino acid sequence of SEQ ID NO: 70. In some embodiments, the anti-BCMA CAR further comprises a hinge domain (e.g., a CD8a hinge domain, or fragment thereof, comprising an amino acid sequence of SEQ ID NO: 69) between the antigen-binding domain and the transmembrane domain. In some embodiments, the intracellular domain further comprises an activation domain, e.g., a CD3z activation domain comprising an amino acid sequence of SEQ ID NO: 72. In some embodiments, the anti-BCMA CAR comprises an amino acid sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 83. In some embodiments, the anti-BCMA CAR comprises the amino acid sequence of SEQ ID NO: 83. In some embodiments, the VH region is encoded bya nucleic acid sequence having at least 90%, 93%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO: 80 and the second VH region is encoded by a nucleic acid sequence having at least 90%, 93%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO: 80. In some embodiments, the anti-BCMA CAR is encoded by a nucleic acid sequence that is at least 95% identical to the nucleic acid sequence of SEQ ID NO: 82. Pharmaceutical compositions, engineered cells, and methods of using said cells or compositions comprising said mRNA encoding an anti-BCMA CAR are also provided herein.

[0087] In some aspects, provided herein is a messenger RNA (mRNA) encoding an anti-BCMA CAR, comprising: a) a first nucleic acid sequence encoding an antigen-binding domain that specifically binds to BCMA, wherein the first nucleic acid sequence comprises the sequence set forth in SEQ ID NO: 3, SEQ ID NO: 5, and SEQ ID NO: 7; b) a second nucleic acid sequence encoding a transmembrane domain; and c) a third nucleic acid sequence encoding a costimulatory domain, wherein the third nucleic acid sequence comprises SEQ ID NO: 11. In some embodiments, the antigen-binding domain comprises a monospecific, bivalent VHH comprising a first heavy chain variable (VH) region and a second VH region each comprising a complementarity determining region 1 (VH CDR1), a VH CDR2, and VH CDR3 as set forth in the amino acid sequences of SEQ ID NO: 63, SEQ ID NO: 65, and SEQ ID NO: 67. In some embodiments, the first and / or the second VH region each comprise an amino acid sequence having at least 90%, 93%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO: 81, or wherein the first and / or the second VH region each comprises the amino acid sequence of SEQ ID NO: 81. In some embodiments, the first VH region comprises the amino acid sequence of SEQ ID NO: 81, and the second VH region comprises the amino acid sequence of SEQ ID NO: 81. In some embodiments, the bivalent VHH comprises a linker between the first and second VH regions. In some embodiments, the linker is a glycine-serine linker, e.g., a glycine-serine linker comprising the sequence of SEQ ID NO: 73. In some embodiments, the antigen-binding domain comprises the amino acid sequence of SEQ ID NO: 84. In some embodiments, the transmembrane domain comprises a CD8a transmembrane domain comprising an amino acid sequence of SEQ ID NO: 70. In some embodiments, the anti-BCMA CAR further comprises a hinge domain (e.g., a CD8a hinge domain, or fragment thereof, comprising an amino acid sequence of SEQ ID NO: 69) between the antigen-binding domain and the transmembrane domain. In some embodiments, the anti-BCMA CAR further comprises an activation domain, e.g., a CD3z activation domain comprising an amino acid sequence of SEQ ID NO: 72. In some embodiments, the anti-BCMA CAR comprises an amino acid sequence that is at least95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 83. In some embodiments, the anti-BCMA CAR comprises the amino acid sequence of SEQ ID NO: 83. In some embodiments, the VH region is encoded by a nucleic acid sequence having at least 90%, 93%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO: 80 and the second VH region is encoded by a nucleic acid sequence having at least 90%, 93%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO: 80. In some embodiments, the anti-BCMA CAR is encoded by a nucleic acid sequence that is at least 95% identical to the nucleic acid sequence of SEQ ID NO: 82. Pharmaceutical compositions, engineered cells, and methods of using said cells or compositions comprising said mRNA encoding an anti-BCMA CAR are also provided herein.

[0088] In some aspects, provided herein is a messenger RNA (mRNA) encoding an anti-BCMA CAR, comprising: a) a first nucleic acid sequence encoding an antigen-binding domain that specifically binds to BCMA, wherein the first nucleic acid sequence comprises the sequence set forth in SEQ ID NO: 80; b) a second nucleic acid sequence encoding a transmembrane domain; and c) a third nucleic acid sequence encoding a costimulatory domain. In some embodiments, the antigen-binding domain comprises a monospecific, bivalent VHH comprising a first heavy chain variable (VH) region and a second VH region each comprising a complementarity determining region 1 (VH CDR1), a VH CDR2, and VH CDR3 as set forth in the amino acid sequences of SEQ ID NO: 63, SEQ ID NO: 65, and SEQ ID NO: 67. In some embodiments, the first and / or the second VH region each comprise an amino acid sequence having at least 90%, 93%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO: 81, or wherein the first and / or the second VH region each comprises the amino acid sequence of SEQ ID NO: 81. In some embodiments, the first and / or the second VH region each comprise an amino acid sequence having at least 90%, 93%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO: 81, or wherein the first and / or the second VH region each comprises the amino acid sequence of SEQ ID NO: 81. In some embodiments, the first VH region comprises the amino acid sequence of SEQ ID NO: 81, and the second VH region comprises the amino acid sequence of SEQ ID NO: 81. In some embodiments, the bivalent VHH comprises a linker between the first and second VH regions. In some embodiments, the linker is a glycine-serine linker, e.g., a glycine-serine linker comprising the sequence of SEQ ID NO: 73. In some embodiments, the antigen-binding domain comprises the amino acid sequence of SEQ ID NO: 84. In some embodiments, the transmembrane domain comprises a CD8a transmembrane domain comprising an amino acid sequence of SEQ ID NO: 70. In some embodiments, the anti-BCMA CAR further comprises a hinge domain (e.g., a CD8ahinge domain, or fragment thereof, comprising an amino acid sequence of SEQ ID NO: 69) between the antigen-binding domain and the transmembrane domain. In some embodiments, the anti-BCMA CAR further comprises an activation domain, e.g., a CD3z activation domain comprising an amino acid sequence of SEQ ID NO: 72. In some embodiments, the anti-BCMA CAR comprises an amino acid sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 83. In some embodiments, the anti-BCMA CAR comprises the amino acid sequence of SEQ ID NO: 83. In some embodiments, the VH region is encoded by a nucleic acid sequence having at least 90%, 93%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO: 80 and the second VH region is encoded by a nucleic acid sequence having at least 90%, 93%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO: 80. In some embodiments, the anti-BCMA CAR is encoded by a nucleic acid sequence that is at least 95% identical to the nucleic acid sequence of SEQ ID NO: 82.

[0089] In some aspects, provided herein is a messenger RNA (mRNA) encoding an anti-BCMA CAR, comprising: a) a first nucleic acid sequence encoding an antigen-binding domain that specifically binds to BCMA, wherein the first nucleic acid sequence comprises the sequence set forth in SEQ ID NO: 80; b) a second nucleic acid sequence encoding a transmembrane domain; and c) a third nucleic acid sequence encoding a costimulatory domain, wherein the third nucleic acid sequence comprises the sequence set forth in SEQ ID NO: 11. In some embodiments, the antigen-binding domain comprises a monospecific, bivalent VHH comprising a first heavy chain variable (VH) region and a second VH region each comprising a complementarity determining region 1 (VH CDR1), a VH CDR2, and VH CDR3 as set forth in the amino acid sequences of SEQ ID NO: 63, SEQ ID NO: 65, and SEQ ID NO: 67. In some embodiments, the first and / or the second VH region each comprise an amino acid sequence having at least 90%, 93%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO: 81, or wherein the first and / or the second VH region each comprises the amino acid sequence of SEQ ID NO: 81. In some embodiments, the first VH region comprises the amino acid sequence of SEQ ID NO: 81, and the second VH region comprises the amino acid sequence of SEQ ID NO: 81. In some embodiments, the bivalent VHH comprises a linker between the first and second VH regions. In some embodiments, the linker is a glycine-serine linker, e.g., a glycine-serine linker comprises the sequence of SEQ ID NO: 73. In some embodiments, the antigen-binding domain comprises the amino acid sequence of SEQ ID NO: 84. In some embodiments, the transmembrane domain comprises a CD8a transmembrane domain comprising an amino acid sequence of SEQ ID NO: 70. In some embodiments, the anti-BCMA CAR further comprises a hinge domain (e.g., a CD8a hingedomain, or fragment thereof, comprising an amino acid sequence of SEQ ID NO: 69) between the antigen-binding domain and the transmembrane domain. In some embodiments, the anti-BCMA CAR further comprises an activation domain, e.g., a CD3z activation domain comprising an amino acid sequence of SEQ ID NO: 72. In some embodiments, the anti-BCMA CAR comprises an amino acid sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 83. In some embodiments, the anti-BCMA CAR comprises the amino acid sequence of SEQ ID NO: 83. In some embodiments, the VH region is encoded by a nucleic acid sequence having at least 90%, 93%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO: 80 and the second VH region is encoded by a nucleic acid sequence having at least 90%, 93%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO: 80. In some embodiments, the anti-BCMA CAR is encoded by a nucleic acid sequence that is at least 95% identical to the nucleic acid sequence of SEQ ID NO: 82.Pharmaceutical compositions, engineered cells, and methods of using said compositions or cells comprising said mRNA encoding an anti-BCMA CAR are also provided herein.BRIEF DESCRIPTION OF THE DRAWINGS

[0090] FIG. 1 shows schematics of the various anti-BCMA CAR construct configurations under evaluation.

[0091] FIG. 2A shows percentage of U266 tumor cell killing of anti-BCMA CAR-T cells that vary in the configuration of the binder, transmembrane, and costimulatory domains. FIG. 2B shows percentage of JeKo-1 tumor cell killing of anti-BCMA CAR-T cells that vary in the configuration of the binder, transmembrane, and costimulatory domains.

[0092] FIGs. 3A-3H show cytokine secretions of GM-CSF, IFN-y, IL-2, and TNF-a of anti-BCMA CAR-T cells that vary in the configuration of the binder, transmembrane, and costimulatory domains.

[0093] FIGs. 4A-4C shows percentage of tumor cell killing of anti-BCMA CAR-T cells that vary in the configuration of the binder and linker.

[0094] FIGs. 5A-5D show cytokine secretions of GM-CSF, IFN-y, IL-2, and TNF-a of anti-BCMA CAR-T cells that vary in the configuration of the binder and linker. FIG. 5E shows the fold change of GM-CSF and IFN-y (Construct 2 vs Benchmark 1B) at E: T of 2: 1 and 1:8.

[0095] FIGs. 6A-6C show percentage of tumor cell killing of anti-BCMA CAR-T cells that vary in the configuration of the linker length.

[0096] FIGs. 7A-7D show cytokine secretions of GM-CSF, IFN-y, IL-2, and TNF-a of BCMA CAR-T cells that vary in the configuration of the linker length.

[0097] FIG. 8 shows the activation of the anti-BCMA CAR-T cells (CD25+ CD69+) following stimulation with tumor cells.

[0098] FIG. 9 shows the percentage of proliferated anti-BCMA CAR-T cells following incubation with tumor cells.

[0099] FIGs. 10A-10C show concentration of GM-CSF, IFN-y, and TNF-a released by anti-BCMA CAR-T cells without antigen stimulation (indicative of tonic signaling).[000100] FIG. 11A shows total tumor burden from the first four rounds of in vitro rechallenge of the anti-BCMA CAR-T cells with RPMI8226 tumor cells. FIG. 11B shows the subsequent four rounds of rechallenge of the anti-BCMA CAR-T cells with RPMI8226 tumor cells.[000101] FIG. 12 shows total tumor burden from in vitro tumor rechallenge of the anti-BCMA CAR-T cells against RPMI-8226 tumor cells on days 3, 5, 7, and 9.[000102] FIG. 13 shows in vivo mouse tumor engraftment of RPMI-8226 tumor cells and indicates the average tumor burden calculated as Total Flux p / s for each group of animals dosed with different constructs from 4 days post tumor engraftment until 35 days post tumor engraftment. T cells were dosed on day 14 post tumor engraftment.[000103] FIG. 14 shows the average tumor burden calculated as Total Flux p / s for each group of animals dosed with different constructs from in vivo tumor re-challenge.[000104] FIG. 15 shows the average tumor burden calculated as Total Flux p / s for each group of animals dosed with different constructs from 1 day post tumor engraftment until 56 days post tumor engraftment. T cells were dosed on day 14 post tumor engraftment.[000105] FIG. 16 shows the average tumor burden calculated as Total Flux p / s for each group of animals dosed with different constructs from in vivo tumor re-challenge.[000106] FIGs. 17A-17C show the average tumor burden calculated as Total Flux p / s for each group of animals dosed with different constructs from 1 day post tumor engraftment until 34 days post tumor engraftment. T cells were dosed on day 14 post tumor engraftment.[000107] FIGs. 18A-18B show fold expansion and viability of total T cells from initiation to harvest demonstrating high yield of allo-CAR-T cells generated from the sequential editing process despite the additional edits.[000108] FIGs. 19A-19C show knock in rates (KI, %) for CAR insertion and knock out rates (KO, %) for endogenous TCR and CIITA (HLA-II). FIG. 19D confirms HLA-A editing by NGS data.[000109] FIG. 20 shows that memory status Tscm (CD45RA+, CD62L+), Tcm (CD45RA-, CD62L+), Tern (CD45RA-, CD62L-), and Ttd (CD45RA+, CD62L-) of CAR inserted cells showed no difference between the autologous and allogeneic anti-BCMA CAR-T cells.[000110] FIGs. 21A-21b show the results from a killing assay of T cells engineered with anti-BCMA CAR constructs with or without Allo edits of RPB scale tested for their cytotoxicity against U266 and JeKo-1 tumor cells.[000111] FIGs. 22A-22D show cytokine secretions of GM-CSF, fFN-y, IL-2, and TNF-ct from engineered anti-BCMA CAR-T cells of RPB scale.[000112] FIG. 23 shows activation of the anti-BCMA CAR-T cells (CD25+CD69+) of RPB scale following stimulation with tumor cells.[000113] FIG. 24 shows percentage of proliferated anti-BCMA CAR-T cells of RPB scale following incubation with tumor cells.[000114] FIGs. 25A-25C show tumor cell killing by Allo-BCMA CAR-T cells with or without knock-out (KO) of TGFBR2 tested for their cytotoxicity against RPMI-8226, MM.1 S, and U266 multiple myeloma (MM) cell lines.[000115] FIGs. 26A-26C show total tumor growth from in vitro tumor rechallenge of Allo-BCMA CAR-T cells with or without knock out (KO) of TGFBR2 against RPMI-8226 tumor cells for a total of 6-8 challenge rounds over 20-28 days.[000116] FIGs. 27A-27B show the average tumor burden calculated as Total Flux p / s for each group of animals dosed with multiple concentrations of two lots (RM10105 and RG3307) of TGFBR2 KO Allo-BCMA CAR-T cells from 7 days post tumor engraftment until 35 days post tumor engraftment. T cells were dosed on day 14 post tumor engraftment.[000117] FIGs. 28A-28B show the average tumor burden calculated as Total Flux p / s for each group of animals dosed with two concentrations of two lots (RM10105 and RG3307) of Allo-BCMA CAR-T cells with or without knock-out (KO) of TGFBR2 from 7 days post tumor engraftment until 35 days post tumor engraftment. T cells were dosed on day 14 post tumor engraftment.[000118] FIGs. 29A-29B show the average tumor burden calculated as Total Flux p / s for each group of animals dosed with 0.3E6 of two lots (RM10105 and RG3307) of TGFBR2 KO Allo-BCMA CAR-T cells from 7 days post tumor engraftment until 35 days post tumor engraftment. T cells were dosed on day 14 post tumor engraftment.[000119] FIGs. 30A-30C show tumor growth after in vitro serial rechallenge of Allo-BCMA CAR-T cells having TGFBR2 knock out (KO) engineered from 24 donors against RPMI-8226 tumor cells; 10 rechallenges over about 38 days at three effector-to-target (E: T) ratios were observed.DETAILED DESCRIPTION[000120] The present disclosure provides for chimeric antigen receptors (CARs), as well as methods and compositions for making immune effector cells (e.g., T-cells and NK cells) comprising CARs. In some embodiments the cell is a T-cell which is engineered to express a CAR, e.g., as described herein. In preferred embodiments, the CAR is an anti-BCMA CAR, e.g., as described herein.[000121] In some embodiments, the disclosure provided herein further relates to the use of CAR technology in conjunction with genome editing using a CRISPR / Cas system, e.g., a Cas9 system. In some embodiments, the present disclosure describes genetically modified anti-BCMA CAR-transduced cells, as well gRNA molecules, compositions, and methods for genetically modifying anti-BCMA CAR-transduced cells. In particular, the gRNA molecules, compositions and methods described herein relate to regulation of expression of (or expression of functional versions of) target molecules that have an effect on the function of a transplanted cell, for example a cell for cancer immunotherapy. In one embodiment, the transplanted cell is an immune effector cell, e.g., an NK cell or T-cell. In one embodiment, the cell is an allogeneic cell. Thus, provided herein are compositions and methods for altering, e.g., inhibiting or reducing, the expression and / or function (e.g., the level of expression of a functional version) of a gene target or a protein encoded by a gene target, thereby improving the efficacy (for example, by reducing or eliminating undesirable immunogenicity (such as a host versus graft response or a graft versus host response)), function, proliferation, stimulation or survival of a transplanted cell, for example a transplanted immune effector cell, e.g., aNK cell or T-cell, e.g., a T-cell engineered to express an anti-BCMA CAR, e.g., an anti-BCMA allogeneic CAR-expressing T-cell for immunotherapy.[000122] In some embodiments, the gene targets are allogeneic T-cell proteins such as an HLA-A, HLA-B, TRAC, or CIITA. Without being bound by theory it is believed that inhibition or elimination of the level of an allogeneic T-cell target or level of expression of an allogeneic T-cell target gene target (e.g., via alteration of the gene) may improve the function of a cell, e.g., a transplanted cell, e.g., a transplanted immune effector cell, e.g., an anti-BCMA CAR-T cell, e.g., an anti-BCMA allogeneic CAR-T cell, by reducing or eliminating agraft v.s'. host response, a host v.s. graft response, or will render said transplanted cell resistant to immunosuppressant therapy.[000123] In an aspect, compositions and methods described herein can be used to improve cell, e.g., T-cell, e.g., an anti-BCMA CAR-engineered T-cell, e.g., allogeneic anti-BCMA CAR-engineered T-cell function (for example, by reducing or eliminating undesirable immunogenicity (such as a host versus graft response or a graft versus host response)), survival, proliferation and / or efficacy by altering the gene of a component of the major histocompatibility complex, e.g., an HLA protein, e.g., HLA-A and / or HLA-B. While not wishing to be bound by theory, it is considered that reduced or absent expression of a mismatch (e.g., one that does not match the type of the subject receiving the cell therapy) HLA protein (or component) reduces or eliminates host vs. graft disease by eliminating host T-cell receptor recognition of and response to mismatched (e.g., allogeneic) graft tissue. This approach, therefore, could be used to generate “off the shelf’ T-cells (Torikai et al., 2012 Blood 119, 5697-5705).[000124] In an aspect, compositions and methods described herein can be used to improve cell, e.g., T-cell, e.g., anti-BCMA CAR-engineered T-cell, e.g., allogeneic anti-BCMA CAR-engineered T-cell, function (for example, by reducing or eliminating undesirable immunogenicity (such as a host versus graft response or a graft versus host response)), survival, proliferation and / or efficacy by altering the gene of a component of the T-cell receptor (TCR), e.g., TRAC. While not wishing to be bound by theory, it is considered that reduced or absent expression of functional T-cell receptor components reduces or eliminates the presence of TCR on the surface of said cell, thereby reducing or preventing graft vs. host disease by eliminating T-cell receptor recognition of and response to host tissues. This approach, therefore, could be used to generate “off the shelf’ T-cells.[000125] In an aspect, compositions and methods described herein can be used to improve cell, e.g., T-cell, e.g., anti-BCMA CAR-engineered T-cell, e.g., allogeneic anti-BCMA CAR-engineered T-cell function (for example, by reducing or eliminating undesirable immunogenicity (such as a host versus graft response or a graft versus host response)), survival, proliferation and / or efficacy by altering the gene encoding a protein that regulates expression of one or more components of the major histocompatibility complex, e.g., CIITA. While not wishing to be bound by theory, it is believed that reducing or eliminating the expression of a regulator of MHC class II expression, e.g., CIITA, will reduce or eliminate the expression of MHC class II molecules on the allogeneic cell, thereby reducing or eliminating expression of a mismatch (e.g., one that does not match the type of the subjectreceiving the cell therapy) MHC class II protein (or component), thereby reducing or eliminating host vs. graft disease by, e.g, eliminating host T-cell receptor recognition of and response to mismatched (e.g, allogeneic) graft tissue, e.g., allogeneic T-cell, e.g., allogeneic anti-BCMA CAR-T cell, as described herein. This approach, therefore, could be used to generate “off the shelf’ T-cells.[000126] In one embodiment, it may be beneficial to reduce or eliminate expression of one or more MHC class I molecules and one or more MHC II molecules, e.g., in a T-cell, e.g., in an allogeneic T-cell, e.g, in an allogeneic anti-BCMA CAR-T cell, e.g, as described herein, to further reduce or eliminate the host versus graft disease response upon administration of the cell. Thus, in embodiments of the cells and methods of the present disclosure, cells may be contacted with a composition of the present disclosure (e.g., a composition comprising a gRNA and a Cas9 molecule) comprising a gRNA molecule, e.g., as described herein, to HLA-A or HLA-B (e.g., such that expression of one or more MHC class I molecules is reduced or eliminated in said cell) and a composition of the present disclosure (e.g., a composition comprising a gRNA and a Cas9 molecule) comprising a gRNA molecule, e.g., as described herein, to CIITA (e.g., such that expression of one or more MHC class II molecules is reduced or eliminated). In embodiments of the cells and methods of the present disclosure, the cell may also be contacted with a composition of the present disclosure (e.g., a composition comprising a gRNA and a Cas9 molecule) comprising a gRNA molecule, e.g., as described herein, to a component of the TCR, e.g., to TRAC (e.g., such that expression of the T-cell receptor, e.g., one or more components of the TCR is reduced or eliminated). In an embodiment, a cell of the present disclosure has reduced or eliminated expression of TCR (e.g., as detected by flow cytometry), reduced or eliminated expression of one or more MHC class I molecules (e.g., as detected by flow cytometry), and reduced or eliminated expression of one or more MHC class II molecules (e.g., as detected by flow cytometry).[000127] In embodiments, the reduced or eliminated expression is measured relative to a similar cell that has not been treated with a composition or CRISPR system of the present disclosure. In embodiments, the cell is an immune effector cell, e.g., a T-cell or NK cell, e.g., a T-cell, e.g., as described herein. In embodiments, the cell is a human cell. In embodiments, the cell is allogeneic relative to a subject to be administered said cell. In embodiments, the reduced or eliminated expression of HLA-A, HLA-B, TRAC, and / or CIITA is accomplished by introducing into said cell a composition, e.g., a CRISPR system, or gRNA of the present disclosure, e.g., as described herein, or by a method as described herein.[000128] In another embodiment, compositions and methods described herein can be used to improve cell, e.g., T-cell, e.g., CAR-transduced T-cell, e.g., allogeneic CAR-transduced T-cell, function (for example, by reducing or eliminating undesirable immunogenicity (such as host versus graft response or a graft versus host response)), survival, proliferation, and / or efficacy by altering the gene of an immune signaling protein, e.g., TGFBR2. This approach, therefore, could be used to generate “off the shelf’ T-cells.[000129] In certain embodiments, the reduced or eliminated expression is measured relative to a similar cell that has not been treated with a composition or CRISPR system of the present disclosure. In embodiments, the cell is an immune effector cell, e.g, a T-cell or NK cell, e.g, a T-cell, e.g., as described herein. In embodiments, the cell is a human cell. In embodiments, the cell is allogeneic relative to a subject to be administered said cell. In embodiments, the reduced or eliminated expression of TGFBR2 is accomplished by introducing into said cell a composition, e.g., a CRISPR system, or gRNA of the present disclosure, e.g., as described herein, or by a method as described herein.[000130] In embodiments in which the cells have reduced or eliminated levels or expression levels of HLA-A, the cells can comprise a genetic modification within genomic coordinates targeted by a guide RNA comprising a guide sequence of any one of SEQ ID NOs: 403, 404, and 412, or a gRNA molecule comprising a guide sequence consisting of 20, 21, 22, 23, 24 or 25 consecutive nucleotides, preferably 20 consecutive nucleotides, of any one of SEQ ID NOs: 403, 404, and 412.[000131] In certain embodiments in which the cells have reduced or eliminated levels or expression levels of HLA-A, the cells can comprise a genetic modification within genomic coordinates targeted by a guide RNA comprising a guide sequence of SEQ ID NO: 403, or a gRNA molecule comprising a guide sequence consisting of 20, 21, 22, 23, 24 or 25 consecutive nucleotides, preferably 20 consecutive nucleotides, of SEQ ID NO: 403.[000132] In embodiments in which the cells have reduced or eliminated levels or expression levels of HLA-B, the cells can comprise a genetic modification within genomic coordinates targeted by a guide RNA comprising a guide sequence of any one of SEQ ID NOs: 405-407, or a gRNA molecule comprising a guide sequence consisting of 17, 18, 19, 20, 21, 22, 23, 24 or 25 consecutive nucleotides, preferably 20 consecutive nucleotides, of any one of SEQ ID NOs: 405-407.[000133] In certain embodiments in which the cells have reduced or eliminated levels or expression levels of HLA-B, the cells can comprise a genetic modification within genomic coordinates targeted by a guide RNA comprising a guide sequence of SEQ ID NO: 406 or agRNA molecule comprising a guide sequence consisting of 17, 18, 19, 20, 21, 22, 23, 24 or 25 consecutive nucleotides, preferably 20 consecutive nucleotides, of SEQ ID NO: 406.[000134] In embodiments in which the cells have reduced or eliminated levels or expression levels of TRAC, the cells can comprise a genetic modification within genomic coordinates targeted by a guide RNA comprising a guide sequence of SEQ ID NO: 413, or a gRNA molecule comprising a guide sequence consisting of 17, 18, 19, 20, 21, 22, 23, 24 or 25 consecutive nucleotides, preferably 20 consecutive nucleotides, of SEQ ID NO: 413. In embodiments in which the cells have reduced or eliminated levels or expression levels of CIITA, the cells can comprise a genetic modification within genomic coordinates targeted by a guide RNA comprising a guide sequence of any one of SEQ ID NOs: 401, 402, and 411, or a gRNA molecule comprising a guide sequence consisting of 17, 18, 19, 20, 21, 22, 23, 24 or 25 consecutive nucleotides, preferably 20 consecutive nucleotides, of any one of SEQ ID NOs: 401, 402, and 411.[000135] In embodiments in which the cells have reduced or eliminated levels or expression levels of CIITA, the cells can comprise a genetic modification within genomic coordinates targeted by a guide RNA comprising a guide sequence of SEQ ID NO: 402, or a gRNA molecule comprising a guide sequence consisting of 17, 18, 19, 20, 21, 22, 23, 24 or 25 consecutive nucleotides, preferably 20 consecutive nucleotides, of SEQ ID NO: 402.[000136] In embodiments in which the cells have reduced or eliminated levels or expression levels of TGFBR2, the cells can comprise a genetic modification within genomic coordinates targeted by a guide RNA comprising a guide sequence of any one of SEQ ID NOs: 301-309, or a gRNA molecule comprising a guide sequence consisting of 17, 18, 19, 20, 21, 22, 23, 24 or 25 consecutive nucleotides, preferably 20 consecutive nucleotides, of any one of SEQ ID NOs: 301-309.[000137] In certain embodiments in which the cells have reduced or eliminated levels or expression levels of TGFBR2, the cells can comprise a genetic modification within genomic coordinates targeted by a guide RNA comprising a guide sequence of SEQ ID NO: 301, or a gRNA molecule comprising a guide sequence consisting of 17, 18, 19, 20, 21, 22, 23, 24 or 25 consecutive nucleotides, preferably 20 consecutive nucleotides, of SEQ ID NO: 301.I. Definitions[000138] Unless stated otherwise, the following terms and phrases as used herein are intended to have the following meanings:[000139] The term “about” or “approximately” means an acceptable error for a particular value as determined by one of ordinary skill in the art, which depends in part on how the value is measured or determined, or a degree of variation that does not substantially affect the properties of the described subject matter, or within the tolerances accepted in the art, e.g., within 10%, 5%, 2%, or 1%. Accordingly, unless indicated to the contrary, the numerical parameters set forth in the following specification and attached claims are approximations that may vary depending upon the desired properties sought to be obtained. At the very least, and not as an attempt to limit the application of the doctrine of equivalents to the scope of the claims, each numerical parameter should at least be construed in light of the number of reported significant digits and by applying ordinary rounding techniques.[000140] The term “or combinations thereof’ as used herein refers to all permutations and combinations of the listed terms preceding the term. For example, “A, B, C, or combinations thereof’ is intended to include at least one of: A, B, C, AB, AC, BC, or ABC, and if order is important in a particular context, also BA, CA, CB, ACB, CBA, BCA, BAC, or CAB.Continuing with this example, expressly included are combinations that contain repeats of one or more item or term, such as BB, AAA, AAB, BBC, CBBA, CABA, and so forth. The skilled artisan will understand that typically there is no limit on the number of items or terms in any combination, unless otherwise apparent from the context.[000141] As used herein, the term “kit” refers to a packaged set of related components, such as one or more polynucleotides or compositions and one or more related materials such as delivery devices (e.g., syringes), solvents, solutions, buffers, instructions, or desiccants.[000142] An “allogeneic” cell, as used herein, refers to a cell originating from a donor subject of the same species as a recipient subject, wherein the donor subject and recipient subject have genetic dissimilarity, e.g., genes at one or more loci that are not identical. Thus, e.g., a cell is allogeneic with respect to the subject to be administered the cell. As used herein, a cell that is removed or isolated from a donor, that will not be re-introduced into the original donor, is considered an allogeneic cell.[000143] The term "allogeneic T-cell target" is used interchangeably herein, refers to a protein that mediates or contributes to a host versus graft response, mediates or contributes to a graft versus host response; and the gene encoding said molecule and its associated regulatory elements, e.g., promoters. It will be understood that the term allogeneic T-cell target refers to the gene (and its associated regulatory elements) encoding an allogeneic T-cell target protein when it is used in connection with a target sequence or gRNA molecule. Without being bound by theory, inhibition or elimination of one or more allogeneic T-celltargets, e.g., by the methods and compositions disclosed herein, may improve the efficacy, survival, function and / or viability of an allogeneic cell, e.g., an allogeneic T-cell, for example, by reducing or eliminating undesirable immunogenicity (such as a host versus graft response or a graft versus host response).[000144] In a non-limiting example, the protein that mediates or contributes to a graft versus host response or host versus graft response is one or more components of the T-cell receptor. In an embodiment, the component of the T-cell receptor is the T-cell receptor alpha, for example the constant domain of the TCR alpha. In an embodiment, the component of the T-cell receptor is the T-cell receptor beta chain, for example the constant domain 1 or constant domain 2 of the TCR beta. Thus, in embodiments where the protein encoded by the allogeneic T-cell target is a component of the TCR, the gene encoding the allogeneic T-cell target may be, for example, TRAC and combinations thereof.[000145] In a non-limiting example, the protein that mediates or contributes to a graft versus host response or host versus graft response is an HLA protein. Examples of HLA proteins include HLA-A and HLA-B. Thus, in embodiments where the allogeneic T-cell target protein is an HLA protein, the gene encoding the allogeneic T-cell target may be, for example, HLA-A, HLA-B, and a combination thereof.[000146] In a non-limiting example, the protein that mediates or contributes to a graft versus host response or host versus graft response is a major histocompatibility complex class II (MHC II) molecule (e.g., HLA-Dx (where x refers to a letter of a MHC II protein, e.g., HLA-DM, HLA-DO, HLA-DR, HLA-DQ and / or HLA-DP)), or a regulatory factor for expression of a MHC II, and combinations thereof. A non-limiting example is CIITA (also referred to herein as C2TA). Thus, in embodiments where the allogeneic T-cell target protein is a CIITA, the gene encoding the allogeneic T-cell target may be, for example, CIITA. An “autologous” cell, as used herein, refers to a cell derived from the same subject to whom the material will later be re-introduced. Thus, e.g., a cell is considered autologous if it is removed from a subject and it will then be re-introduced into the same subject.[000147] The term “BCMA,” as used herein in the context of BCMA protein, refers to the receptor known as B-cell maturation antigen (BCMA) or tumor necrosis factor receptor superfamily member 17 (TNFRSF17). “BCMA” as used herein in the context of nucleic acids refers to the gene encoding the BCMA protein molecule. The human gene has accession number NC_000016.10 (11965210..11968068). Unless otherwise indicated, the term “BCMA” used herein is inclusive of wild type BCMA and mutant versions of BCMA.[000148] “CIITA” or “C2TA,” as used herein, refers to the nucleic acid sequence or protein sequence of “class II major histocompatibility complex transactivator;” the human gene has accession number NC_000016.10 (range 10866208..10941562), reference GRCh38.pl3. The CIITA protein in the nucleus acts as a positive regulator of MHC class II gene transcription and is required for MHC class II protein expression.[000149] As used herein, “MHC” or “MHC molecule(s)” or “MHC protein” or “MHC complex(es),” refers to a major histocompatibility complex molecule (or plural), and includes e.g., MHC class I and MHC class II molecules. In humans, MHC molecules are referred to as “human leukocyte antigen” complexes or “HLA molecules” or “HLA protein.” The use of terms “MHC” and “HLA” are not meant to be limiting; as used herein, the term “MHC” may be used to refer to human MHC molecules, i.e., HLA molecules. Therefore, the terms “MHC” and “HLA” are used interchangeably herein.[000150] The term “HLA- A,” as used herein in the context of HLA- A protein, refers to the MHC class I protein molecule, which is a heterodimer consisting of a heavy chain (encoded by the HLA-A gene) and a light chain i.e., beta-2 microglobulin). The term “HLA-A” or “HLA-A gene,” as used herein in the context of nucleic acids refers to the gene encoding the heavy chain of the HLA-A protein molecule. The HLA-A gene is also referred to as “HLA class I histocompatibility, A alpha chain;” the human gene has accession number NC_000006.12 (29942532..29945870). The HLA-A gene is known to have thousands of different versions (also referred to as “alleles”) across the population (and an individual may receive two different alleles of the HLA-A gene). A public database for HLA-A alleles, including sequence information, may be accessed at IPD-IMGT / HLA:https: / / www.ebi.ac.uk / ipd / imgt / hla / . All alleles of HLA-A are encompassed by the terms “HLA-A” and “HLA-A gene.”[000151]“HLA-B” as used herein in the context of nucleic acids refers to the gene encoding the heavy chain of the HLA-B protein molecule. The HLA-B is also referred to as “HLA class I histocompatibility, B alpha chain;” the human gene has accession number NC_000006.12 (31353875..31357179).[000152] “HLA-C” as used herein in the context of nucleic acids refers to the gene encoding the heavy chain of the HLA-C protein molecule. The HLA-C is also referred to as “HLA class I histocompatibility, C alpha chain;” the human gene has accession number NC_000006.12 (31268749..31272092).[000153] The term “TGF[3R2” or “TGFBR2” as used herein in the context of protein, refers to a transmembrane protein that has a protein kinase domain, forms a heterodimeric complexwith Transforming Growth Factor Beta (TGF-P) receptor type-1, and binds TGF-beta. The term “TGFPR2” or “TGFBR2” as used herein in the context of nucleic acids refers to the gene encoding the Transforming Growth Factor Beta (TGF-P) receptor type-2 protein molecule. The human gene has accession number NC_000003.12 (30606356..30694142).[000154] The term “TRAC,” as used herein in the context of TRAC protein, refers to the T-cell receptor a-chain. “TRAC” as used herein in the context of nucleic acids refers to the gene encoding the T-cell receptor a-chain. A human wild-type TRAC sequence is available at NCBI Gene ID: 28755; Ensembl: ENSG00000277734. T Cell Receptor Alpha Constant, TCRA, IMD7, TRCA and TRA are gene synonyms for TRAC.[000155] As used herein, the term “within the genomic coordinates” includes the boundaries of the genomic coordinate range given. For example, if chr6:29942854-chr6:29942913 is given, the coordinates chr6:29942854- chr6:29942913 are encompassed. Throughout this application, the referenced genomic coordinates are based on genomic annotations in the GRCh38 (also referred to as hg38) assembly of the human genome from the Genome Reference Consortium, available at the National Center for Biotechnology Information website. Tools and methods for converting genomic coordinates between one assembly and another are known in the art and can be used to convert the genomic coordinates provided herein to the corresponding coordinates in another assembly of the human genome, including conversion to an earlier assembly generated by the same institution or using the same algorithm (e.g., from GRCh38 to GRCh37), and conversion of an assembly generated by a different institution or algorithm (e.g., from GRCh38 to NCBI33, generated by the International Human Genome Sequencing Consortium). Available methods and tools known in the art include, but are not limited to, NCBI Genome Remapping Service, available at the National Center for Biotechnology Information website, UCSC LiftOver, available at the UCSC Genome Brower website, and Assembly Converter, available at the Ensembl.org website.[000156] As used herein, the term “homozygous” refers to having two identical alleles of a particular gene.[000157] As used herein, the term “subject” is intended to include living organisms in which an immune response can be elicited, including e.g., mammals, primates, humans.[000158] “Polynucleotide” and “nucleic acid” are used herein to refer to a multimeric compound comprising nucleosides or nucleoside analogs which have nitrogenous heterocyclic bases or base analogs linked together along a backbone, including conventional RNA, DNA, mixed RNA-DNA, and polymers that are analogs thereof. A nucleic acid“backbone” can be made up of a variety of linkages, including one or more of sugarphosphodiester linkages, peptide-nucleic acid bonds (“peptide nucleic acids” or PNA; PCT No. WO 95 / 32305), phosphorothioate linkages, methylphosphonate linkages, or combinations thereof. Sugar moieties of a nucleic acid can be ribose, deoxyribose, or similar compounds with substitutions, e.g., 2’ methoxy or 2’ halide substitutions. Nitrogenous bases can be conventional bases (A, G, C, T, U), analogs thereof (e.g., modified uridines such as 5-methoxyuridine, pseudouridine, or N1-methylpseudouridine, or others); inosine; derivatives of purines or pyrimidines (e.g., N4-methyl deoxyguanosine, deaza- or aza-purines, deaza- or aza-pyrimidines, pyrimidine bases with substituent groups at the 5 or 6 position (e.g., 5-methylcytosine), purine bases with a substituent at the 2, 6, or 8 positions, 2-amino-6-methylaminopurine, O6-methylguanine, 4-thio-pyrimidines, 4-amino-pyrimidines, 4-dimethylhydrazine-pyrimidines, and O4-alkyl-pyrimidines; US Pat. No. 5,378,825 and PCT No. WO 93 / 13121). For general discussion see The Biochemistry of the Nucleic Acids 5-36, Adams et al., ed., 11thed., 1992). Nucleic acids can include one or more “abasic” residues where the backbone includes no nitrogenous base for position(s) of the polymer (US Pat. No.5,585,481). A nucleic acid can comprise only conventional RNA or DNA sugars, bases and linkages, or can include both conventional components and substitutions (e.g., conventional bases with 2’ methoxy linkages, or polymers containing both conventional bases and one or more base analogs). Nucleic acid includes “locked nucleic acid” (LNA), an analogue containing one or more LNA nucleotide monomers with a bicyclic furanose unit locked in an RNA mimicking sugar conformation, which enhance hybridization affinity toward complementary RNA and DNA sequences (Vester and Wengel, 2004, Biochemistry 43(42): 13233-41). RNA and DNA have different sugar moieties and can differ by the presence of uracil or analogs thereof in RNA and thymine or analogs thereof in DNA.[000159] “Guide RNA”, “gRNA”, and simply “guide” are used herein interchangeably to refer to, for example, the guide that directs an RNA-guided DNA binding agent to a target DNA and can be a single guide RNA, or the combination of a crRNA and a trRNA (also known as tracrRNA). Exemplary gRNAs include Class II Cas nuclease guide RNAs, in modified or unmodified forms. The crRNA and trRNA may be associated as a single RNA molecule (single guide RNA, sgRNA) or in two separate RNA strands (dual guide RNA, dgRNA). “Guide RNA” or “gRNA” refers to each type. The trRNA may be a naturally occurring sequence, or a trRNA sequence with modifications or variations compared to naturally-occurring sequences.[000160] As used herein, a “guide sequence” refers to a sequence within a guide RNA that is complementary to a target sequence and functions to direct a guide RNA to a target sequence for binding or modification (e.g., cleavage) by an RNA-guided DNA binding agent. A “guide sequence” may also be referred to as a “targeting sequence,” or a “spacer sequence.” A guide sequence can be 19, 20, 21, 22, 23, or 24, or 25 nucleotides in length, e.g., in the case of Neisseria meningitides (Nme) or S. pyogenes (Spy). In some embodiments, the Nme Cas9 guide sequence comprises at least 22, 23, or 24 contiguous nucleotides of a sequence selected from SEQ ID NOs: 301, 401-407, and 601-774. In some embodiments, the Spy Cas9 guide sequence comprises at least 18, 19, or 20 contiguous nucleotides of a sequence selected from SEQ ID NOs: 302-309 or 411-415. In some embodiments, the target sequence is in a gene or on a chromosome, for example, and is complementary to the guide sequence. In some embodiments, the degree of complementarity or identity between a guide sequence and its corresponding target sequence is at least 80%, 85%, 90%, or 95%. For example, in some embodiments, the guide sequence comprises a sequence 24 contiguous nucleotides of a sequence selected from SEQ ID NO: 301- 401-407. and 601-774. In some embodiments, the guide sequence and the target region may be 100% complementary or identical. In other embodiments, the guide sequence and the target region may contain at least one mismatch, i.e., one nucleotide that is not identical or not complementary, depending on the reference sequence. For example, the guide sequence and the target sequence may contain 1-2, preferably no more than 1 mismatch, where the total length of the target sequence is 19, 20, 21, 22, 23, or 24, nucleotides, or more. In some embodiments, the guide sequence and the target region may contain 1-2 mismatches where the guide sequence comprises at least 24 nucleotides, or more. In some embodiments, the guide sequence and the target region may contain 1-2 mismatches where the guide sequence comprises 24 nucleotides. That is, the guide sequence and the target region may form a duplex region having base pairs, or more. In certain embodiments, the duplex region may include 1-2 mismatches such that guide strand and target sequence are not fully complementary. Mismatch positions are known in the art as provided in, for example, PAM distal mismatches tend to be better tolerated than PAM proximal matches. Mismatch tolerances at other positions are known in the art (see, e.g., Edraki et al., 2019. Mol. Cell, 73:1-13).[000161] Target sequences for RNA-guided DNA binding agents include both the positive and negative strands of genomic DNA (z.e., the sequence given and the sequence’s reverse compliment), as a nucleic acid substrate for an RNA-guided DNA binding agent is a double stranded nucleic acid. Accordingly, where a guide sequence is said to be “complementary toa target sequence”, it is to be understood that the guide sequence may direct a guide RNA to bind to the reverse complement of a target sequence. Thus, in some embodiments, where the guide sequence binds the reverse complement of a target sequence, the guide sequence is identical to certain nucleotides of the target sequence (e.g., the target sequence not including the PAM) except for the substitution of U for T in the guide sequence.[000162] As used herein, an “RNA-guided DNA binding agent” means a polypeptide or complex of polypeptides having RNA and DNA binding activity, or a DNA-binding subunit of such a complex, wherein the DNA binding activity is sequence-specific and depends on the presence of a PAM and the sequence of the guide RNA. Exemplary RNA-guided DNA binding agents include Cas cleavases / nickases and inactivated forms thereof (“dCas DNA binding agents”). “Cas nuclease”, also called “Cas protein” as used herein, encompasses Cas cleavases, Cas nickases, and dCas DNA binding agents. Cas cleavases / nickases and dCas DNA binding agents include a Csm or Cmr complex of a type III CRISPR system, the Cas 10, Csml, or Cmr2 subunit thereof, a Cascade complex of a type I CRISPR system, the Cas3 subunit thereof, and Class 2 Cas nucleases.[000163] As used herein, a “Class 2 Cas nuclease” is a single-chain polypeptide with RNA-guided DNA binding activity. Class 2 Cas nucleases include Class 2 Cas cleavases / nickases (e.g., H840A, D10A, or N863A variants of Spy Cas9 and D16A and H588A of Nme Cas9, e.g., Nme2 Cas9), which further have RNA-guided DNA cleavases or nickase activity, and Class 2 dCas DNA binding agents, in which cleavase / nickase activity is inactivated. Class 2 Cas nucleases include, for example, Cas9, Cpfl, C2cl, C2c2, C2c3, HF Cas9 (e.g., N497A, R661A, Q695A, Q926A variants), HypaCas9 (e.g., N692A, M694A, Q695A, H698A variants), eSPCas9(1.0) (e.g., K810A, K1003A, R1060A variants), and eSPCas9(l.l) (e.g., K848A, K1003A, R1060 A variants) proteins and modifications thereof. Cpfl protein, Zetsche et al., Cell, 163: 1-13 (2015), is homologous to Cas9, and contains a RuvC-like nuclease domain. Cpfl sequences of Zetsche are incorporated by reference in their entirety. See, e.g., Zetsche, Tables S1 and S3. See, e.g., Makarova et al., Nat Rev Microbiol, 13(11): 722-36 (2015); Shmakov et al., Molecular Cell, 60:385-397 (2015).[000164] Several Cas9 orthologs have been obtained from N. meningitidis (Esvelt etal., NAT. METHODS, vol. 10, 2013, 1116 - 1121; Hou etal., PNAS, vol. 110, 2013, pages 15644 - 15649) (NmelCas9, Nme2Cas9, and Nme3Cas9). TheNme2Cas9 ortholog functions efficiently in mammalian cells, recognizes an N4CC PAM, and can be used for in vivo editing with cognate gRNAs (Ran etal., NATURE, vol. 520, 2015, pages 186 - 191; Kim et al., NAT. COMMUN., vol. 8, 2017, pages 14500). Nme2Cas9 can be specific and selective,e.g., capable of low off-target editing (Lee etal., MOL. THER., vol. 24, 2016, pages 645 -654; Kim etal., 2017). See also e.g., WO / 2020081568 (e.g., pages 28 and 42), describing an Nme2Cas9 D16A nickase, the contents of which are hereby incorporated by reference in its entirety. Throughout, “NmeCas9” or “Nme Cas9” is generic and encompasses any type of NmeCas9, including, NmelCas9, Nme2Cas9, and Nme3Cas9.[000165] Exemplary nucleotide and polypeptide sequences of Cas9 molecules are provided in Table 10. Methods for identifying alternate nucleotide sequences encoding Cas9 polypeptide sequences, including alternate naturally occurring variants, are known in the art. Sequences with at least 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identity to any of the Cas9 nucleic acid sequences, or nucleic acid sequences encoding the amino acid sequences provided herein are also contemplated.[000166] As used herein, the term “editor” refers to an agent comprising a polypeptide that is capable of making a modification within a DNA sequence. In some embodiments, the editor is a cleavase, such as a Cas9 cleavase. In some embodiments, the editor is capable of deaminating a base within a DNA molecule, and it may be called a base editor. In some embodiments, the editor is capable of deaminating a cytosine (C) in DNA. In some embodiments, the editor is a fusion protein comprising an RNA-guided nickase fused to a cytidine deaminase. In some embodiments, the editor is a fusion protein comprising an RNA-guided nickase fused to an APOBEC3 A deaminase (A3 A). In some embodiments, the editor comprises a Cas9 nickase fused to an APOBEC3 A deaminase (A3 A). In some embodiments, the editor is a fusion protein comprising an RNA-guided nickase fused to a cytidine deaminase and a UGI. In some embodiments, the editor lacks a UGI.[000167] As used herein, a “cytidine deaminase” means a polypeptide or complex of polypeptides that is capable of cytidine deaminase activity, that is catalyzing the hydrolytic deamination of cytidine or deoxycytidine, typically resulting in uridine or deoxyuridine. Cytidine deaminases encompass enzymes in the cytidine deaminase superfamily, and in particular, enzymes of the APOBEC family (APOBEC1, APOBEC2, APOBEC4, and APOBEC3 subgroups of enzymes), activation-induced cytidine deaminase (AID or AICDA) and CMP deaminases (see, e.g., Conticello et al., Mol. Biol. Evol. 22:367-77, 2005;Conticello, Genome Biol. 9:229, 2008; Muramatsu et al., J. Biol. Chem. 274: 18470-6, 1999); Carrington etal., Cells 9:1690 (2020)). In some embodiments, variants of any known cytidine deaminase or APOBEC protein are encompassed. Variants include proteins having a sequence that differs from wild-type protein by one or several mutations (i.e., substitutions, deletions, insertions), such as one or several single point substitutions. For instance, ashortened sequence could be used, e.g., by deleting N-terminal, C-terminal, or internal amino acids, preferably one to four amino acids at the C-terminus of the sequence. As used herein, the term “variant” refers to allelic variants, splicing variants, and natural or artificial mutants, which are homologous to a reference sequence. The variant is “functional” in that it shows a catalytic activity of DNA editing.[000168] As used herein, the term “APOBEC3A” refers to a cytidine deaminase such as the protein expressed by the human A3 A gene. The APOBEC3 A may have catalytic DNA editing activity. An amino acid sequence of APOBEC3 A has been described (UniPROT accession ID: p31941) and is included herein as SEQ ID NO: 850. In some embodiments, the APOBEC3 A protein is a human APOBEC3 A protein or a wild-type protein. Variants include proteins having a sequence that differs from wild-type APOBEC3 A protein by one or several mutations (i.e., substitutions, deletions, insertions), such as one or several single point substitutions. For instance, a shortened APOBEC3A sequence could be used, e.g., by deleting N-terminal, C-terminal, or internal amino acids, preferably one to four amino acids at the C-terminus of the sequence. As used herein, the term “variant” refers to allelic variants, splicing variants, and natural or artificial mutants, which are homologous to an APOBEC3 A reference sequence. The variant is “functional” in that it shows a catalytic activity of DNA editing. In some embodiments, an APOBEC3 A (such as a human APOBEC3 A) has a wild-type amino acid position 57 (as numbered in the wild-type sequence). In some embodiments, an APOBEC3 A (such as a human APOBEC3 A) has an asparagine at amino acid position 57 (as numbered in the wild-type sequence).[000169] As used herein, a “nickase” is an enzyme that creates a single-strand break (also known as a “nick”) in double strand DNA, i.e., cuts one strand but not the other of the DNA double helix. As used herein, an “RNA-guided DNA nickase” means a polypeptide or complex of polypeptides having DNA nickase activity, wherein the DNA nickase activity is sequence-specific and depends on the sequence of the RNA. Exemplary RNA-guided DNA nickases include Cas nickases. Class 2 Cas nickases include, polypeptides in which either the HNH or RuvC catalytic domain is inactivated, for example, Cas9 (e.g., H840A, D10A, or N863A variants of SpyCas9 or D16A variant of NmeCas9). Exemplary amino acid substitutions in the HNH or HNH-like nuclease domain or RuvC or RuvC-like domains for N. meningitidis include Nme2Cas9 D16A (HNH nickase) and Nme2Cas9 H588A (RuvC nickase). Cpfl, C2cl, C2c2, C2c3, HF Cas9 (e.g., N497A, R661A, Q695A, Q926A variants), HypaCas9 (e.g., N692A, M694A, Q695A, H698A variants), eSPCas9(1.0) (e.g, K810A, K1003A, R1060A variants), and eSPCas9(l.l) (e.g., K848A, K1003A, R1060A variants)proteins and modifications thereof. Cpfl protein, Zetsche et al., Cell, 163: 1-13 (2015), is homologous to Cas9, and contains a RuvC-like protein domain. Cpfl sequences of Zetsche are incorporated by reference in their entirety. See, e.g., Zetsche, Tables SI and S3. “Cas9” encompasses S. pyogenes (Spy) Cas9, the variants of Cas9 listed herein, and equivalents thereof. See, e.g., Makarova et al., Nat Rev Microbiol, 13(11): 722-36 (2015); Shmakov et al., Molecular Cell, 60:385-397 (2015).[000170] As used herein, the term “fusion protein” refers to a hybrid polypeptide which comprises protein domains from at least two different proteins. One protein may be located at the amino-terminal (N-terminal) portion of the fusion protein or at the carboxy-terminal (C-terminal) protein thus forming an “amino-terminal fusion protein” or a “carboxy-terminal fusion protein,” respectively. Any of the proteins provided herein may be produced by any method known in the art. For example, the proteins provided herein may be produced via recombinant protein expression and purification, which is especially suited for fusion proteins comprising a peptide linker. Methods for recombinant protein expression and purification are well known, and include those described by Green and Sambrook, Molecular Cloning: A Laboratory Manual (4th ed., Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N. Y. (2012)), the entire contents of which are incorporated herein by reference.[000171] The term "chimeric antigen receptor," or alternatively " CAR," refers to a set of polypeptides, typically two in the simplest embodiments, which, when in an immune effector cell, provides the cell with specificity for a target cell, typically a cancer cell, and with intracellular signal generation. In some embodiments, a CAR comprises at least an extracellular antigen binding domain, a transmembrane domain and an intracellular domain (also referred to herein as “an intracellular domain”) comprising a functional signaling domain derived from a stimulatory molecule (e.g., an activation domain) and / or costimulatory molecule (e.g., a costimulatory domain) as defined below. In some aspects, the set of polypeptides are contiguous with each other. In some embodiments, the set of polypeptides includes a dimerization switch that, upon the presence of a dimerization molecule, can couple the polypeptides to one another, e.g., can couple an antigen binding domain to an intracellular domain. In one aspect, the stimulatory molecule is the zeta chain associated with the T-cell receptor complex. In one aspect, the cytoplasmic signaling domain further comprises one or more functional signaling domains derived from at least one costimulatory molecule as defined below. In one aspect, the costimulatory molecule is chosen from the costimulatory molecules described herein, e.g., 41BB (i.e., CD137), CD27 and / or CD28. In one aspect, the CAR comprises a chimeric fusion protein comprising anextracellular antigen binding domain, a transmembrane domain and an intracellular domain comprising a functional signaling domain derived from a stimulatory molecule. In one aspect, the CAR comprises a chimeric fusion protein comprising an extracellular antigen binding domain, a transmembrane domain and an intracellular domain comprising a functional signaling domain derived from a costimulatory molecule and a functional signaling domain derived from a stimulatory molecule. In one aspect, the CAR comprises a chimeric fusion protein comprising an extracellular antigen binding domain, a transmembrane domain and an intracellular domain comprising two functional signaling domains derived from one or more costimulatory molecule(s) and a functional signaling domain derived from a stimulatory molecule. In one aspect, the CAR comprises a chimeric fusion protein comprising an extracellular antigen binding domain, a transmembrane domain and an intracellular domain comprising at least two functional signaling domains derived from one or more costimulatory molecule(s) and a functional signaling domain derived from a stimulatory molecule. In one aspect the CAR comprises an optional leader sequence at the amino-terminus (N-ter) of the CAR fusion protein. In one aspect, the CAR further comprises a leader sequence at the N-terminus of the extracellular antigen binding domain, wherein the leader sequence is optionally cleaved from the antigen binding domain (e.g., an scFv) during cellular processing and localization of the CAR to the cellular membrane.[000172] A CAR that comprises an antigen binding domain (e.g., a VHH, an scFv, or TCR) that targets a specific tumor marker X, such as those described herein, is also referred to as an anti-X CAR. For example, a CAR that comprises an antigen binding domain that targets CD 19 is referred to as an anti-CD19 CAR. As another example, a CAR that comprises an antigen binding domain that targets BCMA is referred to as an anti-BCMA CAR. The term "signaling domain" refers to the functional portion of a protein which acts by transmitting information within the cell to regulate cellular activity via defined signaling pathways by generating second messengers or functioning as effectors by responding to such messengers.[000173] The term “linker,” as used herein, refers to a chemical group or a molecule linking two adjacent molecules or moi eties. Typically, the linker is positioned between, or flanked by, two groups, molecules, or other moieties and connected to each one via a covalent bond. In some embodiments, the linker is an amino acid or a plurality of amino acids (e.g., a peptide or protein) such as a 16-amino acid residue “XTEN” linker, or a variant thereof (See, e.g., the Examples; and Schell enberger et al. A recombinant polypeptide extends the in vivo half-life of peptides and proteins in a tunable manner. Nat. Biotechnol. 27, 1186-1190 (2009)). In some embodiments, the XTEN linker comprises the sequenceSGSETPGTSESATPES (SEQ ID NO: 901), SGSETPGTSESA (SEQ ID NO: 902), or SGSETPGTSESATPEGGSGGS (SEQ ID NO: 903). In some embodiments, the linker is a peptide linker comprising one or more sequences selected from SEQ ID NOs: 901-991.[000174] As used herein, the term “uracil glycosylase inhibitor” or “UGI” refers to a protein that is capable of inhibiting a uracil-DNA glycosylase (UDG) base-excision repair enzyme.[000175] As used herein, “open reading frame” or “ORF” of a gene refers to a sequence consisting of a series of codons that specify the amino acid sequence of the protein that the gene codes for. The ORF begins with a start codon (e.g., ATG in DNA or AUG in RNA) and ends with a stop codon, e.g., TAA, TAG or TGA in DNA or UAA, UAG, or UGA in RNA.[000176] As used herein, “ribonucleoprotein” (RNP) or “RNP complex” refers to a guide RNA together with an RNA-guided DNA binding agent, such as a Cas nuclease, e.g., a Cas cleavase, Cas nickase, or dCas DNA binding agent (e.g., Cas9). In some embodiments, the guide RNA guides the RNA-guided DNA binding agent such as Cas9 to a target sequence, and the guide RNA hybridizes with the target sequence and the agent binds to the target sequence; in cases where the agent is a cleavase or nickase, binding can be followed by cleaving or nicking.[000177] As used herein, a first sequence is considered to “comprise a sequence with at least X% identity to” a second sequence if an alignment of the first sequence to the second sequence shows that X% or more of the positions of the second sequence in its entirety are matched by the first sequence. For example, the sequence AAGA comprises a sequence with 100% identity to the sequence AAG because an alignment would give 100% identity in that there are matches to all three positions of the second sequence. The differences between RNA and DNA (generally the exchange of uridine for thymidine or vice versa) and the presence of nucleoside analogs such as modified uridines do not contribute to differences in identity or complementarity among polynucleotides as long as the relevant nucleotides (such as thymidine, uridine, or modified uridine) have the same complement (e.g., adenosine for all of thymidine, uridine, or modified uridine; another example is cytosine and 5-methylcytosine, both of which have guanosine or modified guanosine as a complement). Thus, for example, the sequence 5’-AXG where X is any modified uridine, such as pseudouridine, Nl-methyl pseudouridine, or 5-methoxyuridine, is considered 100% identical to AUG in that both are perfectly complementary to the same sequence (5’-CAU). Exemplary alignment algorithms are the Smith-Waterman and Needleman-Wunsch algorithms, which are well-known in the art. One skilled in the art will understand what choice of algorithm and parameter settings are appropriate for a given pair of sequences to be aligned; for sequences of generally similarlength and expected identity >50% for amino acids or >75% for nucleotides, the Needleman-Wunsch algorithm with default settings of the Needleman-Wunsch algorithm interface provided by the EBI at the www.ebi.ac.uk web server is generally appropriate.[000178] “Messenger RNA” or “mRNA” is used herein to refer to a polynucleotide and comprises an open reading frame that can be translated into a polypeptide (i.e., can serve as a substrate for translation by a ribosome and amino-acylated tRNAs). mRNA can comprise one or more modifications as provided below.[000179] As used herein, a “genetic modification” is a change at the DNA level, e.g., induced by a CRISPR / Cas9 gRNA and Cas9 system. A genetic modification may comprise an insertion, deletion, or substitution (i.e., base sequence substitution, i.e., mutation), typically within a defined sequence or genomic locus. A genetic modification changes the nucleic acid sequence of the DNA. A genetic modification may be at a single nucleotide position. A genetic modification may be at multiple nucleotides, e.g., 2, 3, 4, 5 or more nucleotides, typically in close proximity to each other, e.g, contiguous nucleotides. A genetic modification can be in a coding sequence, e.g., an exon sequence. A genetic modification can be at a splice site, i.e., sufficiently close to a splice acceptor site or a splice donor site to disrupt splicing. A genetic modification can include insertion of a nucleotide sequence not endogenous to the genomic locus, e.g., insertion of a coding sequence of a heterologous open reading frame or gene. As used herein, a genetic modification can be used to prevent translation of an endogenous full-length protein having an amino acid sequence of the full-length protein prior to genetic modification of the genomic locus. Prevention of translation of an endogenous full-length protein or gene product includes prevention of translation of a protein or gene product of any length. Translation of an endogenous full-length protein can be prevented, for example, by a frameshift mutation that results in the generation of a premature stop codon or by generation of a nonsense mutation. Translation of an endogenous full-length protein can be prevented by disruption of splicing. Translation of an endogenous full-length protein can be prevented by the insertion of a heterologous coding sequence. Translation of an endogenous full-length protein, e.g., when the endogenous full-length protein contains an unwanted mutation, can be prevented by making a change at one or more positions to change an endogenous full-length protein coding sequence to provide a modified full-length coding sequence different from the endogenous sequence present in the cell, e.g., correction of a point mutation. Translation of an endogenous full-length protein can be prevented by altering the splicing of the endogenous full-length protein to produce a different protein by alternative splicing.[000180] As used herein, “indel” refers to an insertion or deletion mutation consisting of a number of nucleotides that are either inserted, deleted, or inserted and deleted, e.g., at the site of double-stranded breaks (DSBs), in a target nucleic acid. As used herein, when indel formation results in an insertion, the insertion is a random insertion at the site of a DSB and may or may not be directed by or based on a template sequence.[000181] As used herein, a “heterologous coding sequence” refers to a coding sequence that has been introduced as an exogenous source within a cell (e.g., inserted at a genomic locus such as a safe harbor locus including a TCR gene locus). That is, the introduced coding sequence is heterologous with respect to at least its insertion site. A polypeptide expressed from such heterologous coding sequence gene is referred to as a “heterologous polypeptide.” The heterologous coding sequence can be naturally occurring or engineered, and can be wildtype or a variant. The heterologous coding sequence may include nucleotide sequences other than the sequence that encodes the heterologous polypeptide (e.g., an internal ribosomal entry site). The heterologous coding sequence can be a coding sequence that occurs naturally in the genome, as a wild-type or a variant (e.g., mutant). For example, although the cell contains the coding sequence of interest (as a wild-type or as a variant), the same coding sequence or variant thereof can be introduced as an exogenous source for, e.g., expression at a locus that is highly expressed. The heterologous coding sequence can also be a coding sequence that is not naturally occurring in the genome, or that expresses a heterologous polypeptide that does not naturally occur in the genome. “Heterologous coding sequence”, “exogenous coding sequence”, and “transgene” are used interchangeably. In some embodiments, the heterologous coding sequence or transgene includes an exogenous nucleic acid sequence, e.g., a nucleic acid sequence is not endogenous to the recipient cell. In some embodiments, the heterologous coding sequence or transgene includes an exogenous nucleic acid sequence, e.g., a nucleic acid sequence that does not naturally occur in the recipient cell. For example, a heterologous coding sequence may be heterologous with respect to its insertion site and with respect to its recipient cell.[000182] As used herein, “reduced or eliminated” expression of a protein on a cell refers to a partial or complete loss of expression of the protein relative to an unmodified cell. In some embodiments, the surface expression of a protein on a cell is measured by flow cytometry and has “reduced” or “eliminated” surface expression relative to an unmodified cell as evidenced by a reduction in fluorescence signal upon staining with the same antibody against the protein. A cell that has “reduced” or “eliminated” surface expression of a protein by flow cytometry relative to an unmodified cell may be referred to as “negative” for expression ofthat protein as evidenced by a fluorescence signal similar to a cell stained with an isotype control antibody. The “reduction” or “elimination” of protein expression can be measured by other known techniques in the field with appropriate controls known to those skilled in the art.[000183] As used herein, “knockdown” refers to a decrease in expression of a particular gene target or protein encoded by a gene target (e.g., protein, mRNA, or both), e.g., as compared to expression of an unedited target sequence. Knockdown of a protein can be measured by detecting total cellular amount of the protein from a sample, such as a tissue, fluid, or cell population of interest. It can also be measured by measuring a surrogate, marker, or activity for the protein. Methods for measuring knockdown of mRNA are known and include analyzing mRNA isolated from a sample of interest. In some embodiments, “knockdown” may refer to some loss of expression of a particular gene target, for example a decrease in the amount of mRNA transcribed or a decrease in the amount of protein expressed by a cell or population of cells (including in vivo populations such as those found in tissues).[000184] As used herein, “knockout” refers to a loss of expression from a particular gene or of a particular protein in a cell. Knockout can result in a decrease in expression below the level of detection of the assay. Knockout can be measured either by detecting total cellular amount of a protein in a cell, a tissue or a population of cells.[000185] As used herein, a “target sequence” or “genomic target sequence” refers to a sequence of nucleic acid in a target gene that has complementarity to the guide sequence of the gRNA. The interaction of the target sequence and the guide sequence directs an RNA-guided DNA binding agent to bind, and potentially nick or cleave (depending on the activity of the agent), within the target sequence.[000186] As used herein, “treatment” refers to any administration or application of a therapeutic for disease or disorder in a subject, and includes inhibiting the disease, arresting its development, relieving one or more symptoms of the disease, curing the disease, or preventing one or more symptoms of the disease, including recurrence of the symptom.[000187] Reference will now be made in detail to certain embodiments of the present disclosure, examples of which are illustrated in the accompanying drawings. While the present disclosure is described in conjunction with the illustrated embodiments, it will be understood that they are not intended to limit the present disclosure to those embodiments. On the contrary, the present disclosure is intended to cover all alternatives, modifications, and equivalents, which may be included within the present disclosure as defined by the appended claims and included embodiments.[000188] Before describing the present teachings in detail, it is to be understood that the disclosure is not limited to specific compositions or process steps, as such may vary. It should be noted that, as used in this specification and the appended claims, the singular form “a”, “an” and “the” include plural references unless the context clearly dictates otherwise. Thus, for example, reference to “a conjugate” includes a plurality of conjugates and reference to “a cell” includes a plurality of cells and the like.[000189] Numeric ranges are inclusive of the numbers defining the range. Measured and measurable values are understood to be approximate, taking into account significant digits and the error associated with the measurement. Also, the use of “comprise”, “comprises”, “comprising”, “contain”, “contains”, “containing”, “include”, “includes”, and “including” are not intended to be limiting. It is to be understood that both the foregoing general description and detailed description are exemplary and explanatory only and are not restrictive of the teachings.[000190] Unless specifically noted in the specification, embodiments in the specification that recite “comprising” various components are also contemplated as “consisting of’ or “consisting essentially of’ the recited components; embodiments in the specification that recite “consisting of’ various components are also contemplated as “comprising” or “consisting essentially of’ the recited components; and embodiments in the specification that recite “consisting essentially of’ various components are also contemplated as “consisting of’ or “comprising” the recited components (this interchangeability does not apply to the use of these terms in the claims). The term “or” is used in an inclusive sense, z.e., equivalent to “and / or,” unless the context clearly indicates otherwise.[000191] The section headings used herein are for organizational purposes only and are not to be construed as limiting the desired subject matter in any way. In the event that any material incorporated by reference contradicts any term defined in this specification or any other express content of this specification, this specification controls. While the present teachings are described in conjunction with various embodiments, it is not intended that the present teachings be limited to such embodiments. On the contrary, the present teachings encompass various alternatives, modifications, and equivalents, as will be appreciated by those of skill in the art.II. Anti-BCMA Chimeric Antigen Receptors (CARs)[000192] The present disclosure describes new CARs comprising an anti-BCMA antigen binding protein fused to a CAR scaffold and generally with different componenttransmembrane domains and intracellular domains. The resulting CARs provide for enhanced cytotoxicity against tumor cells, both in vitro and in vivo.[000193] In general, aspects of the present disclosure pertain to or include an isolated nucleic acid molecule encoding an anti-BCMA CAR, wherein the anti-BCMA CAR comprises an antigen binding domain (e.g., antibody or antibody fragment) that binds to a tumor antigen as described herein, i.e., BCMA, a transmembrane domain (e.g., a transmembrane domain described herein), and an intracellular domain (e.g., an intracellular domain described herein) (e.g., an intracellular domain comprising a costimulatory domain (e.g., a costimulatory domain described herein) and / or a primary signaling domain (e.g., an activation domain described herein). In certain aspects, the anti-BCMA CAR comprises an antigen binding domain which is a monospecific, bivalent VHH (two BCMA binding VH domains connected via a linker) which binds to human BCMA. In other aspects, the present disclosure includes: host cells containing the above nucleic acids and isolated proteins encoded by such nucleic acid molecules. CAR nucleic acid constructs, encoded proteins, containing vectors, host cells, pharmaceutical compositions, and methods of administration and treatment related to the present disclosure are disclosed in detail in International Patent Application Publication No. WO2015142675, which is incorporated by reference in its entirety.[000194] In one aspect, the present disclosure pertains to an isolated nucleic acid molecule encoding an anti-BCMA CAR, wherein the anti-BCMA CAR comprises an antigen binding domain (e.g., antibody or antibody fragment) that binds to a tumor-supporting antigen (e.g., a tumor-supporting antigen, e.g., BCMA, as described herein), a transmembrane domain (e.g, a transmembrane domain described herein), and an intracellular domain (e.g, an intracellular domain described herein) (e.g., an intracellular domain comprising a costimulatory domain (e.g., a costimulatory domain described herein) and / or a primary signaling domain (e.g., an activation domain described herein). In other aspects, the present disclosure features polypeptides encoded by such nucleic acids and host cells containing such nucleic acids and / or polypeptides.[000195] The present disclosure provides cells, e.g., immune effector cells (e.g., T-cells, NK cells), comprising a gRNA molecule or CRISPR system as described herein, or comprising a genetic modification within genomic coordinates targeted by a guide RNA or CRISPR system as described herein, that are further engineered to contain one or more anti-BCMA CARs that direct the immune effector cells to undesired cells (e.g., cancer cells). This is achieved through an antigen binding domain on the anti-BCMA CAR that is specific for a cancer associated antigen, e.g., BCMA.[000196] The disclosed anti-BCMA CARs further comprise a transmembrane domain, or a functional fragment thereof. In some embodiments, the transmembrane domain is a CD8a or CD28 transmembrane domain. The disclosed anti-BCMA CARs further comprise a hinge domain, or a functional fragment thereof, between the antigen binding protein and the transmembrane domain.[000197] The disclosed anti-BCMA CARs may further comprise an intracellular domain comprising one or more of an activation domain and / or a costimulatory signaling domain (or a costimulatory domain). In some embodiments, the intracellular domain comprises a sequence encoding an activation domain. In some embodiments, the intracellular domain comprises a costimulatory signaling domain. In some embodiments, the intracellular domain comprises an activation domain and a costimulatory signaling domain. In some embodiments, the intracellular domain comprises a costimulatory domain, or a functional fragment thereof, wherein the costimulatory domain is a 4-1BB or CD28 costimulatory domain.[000198] The present disclosure also encompasses isolated nucleic acid molecules comprising sequences encoding the disclosed amino acid sequences and CARs. It should be noted that where an amino acid sequence is described, the nucleic acid sequence that encodes the amino acid sequence is also included.[000199] The disclosed anti-BCMA CARs further comprise a transmembrane domain, or a functional fragment thereof. In some embodiments, the transmembrane domain is a CD8a or CD28 transmembrane domain.[000200] In some embodiments, the present disclosure provides for an engineered cell comprising the nucleic acid, the mRNA, or the expression vector. In some embodiments, the present disclosure provides for an engineered cell comprising the anti-BCMA CAR. In some embodiments, the present disclosure provides for an engineered cell comprising the anti-BCMA CAR, wherein the cell is transduced with an expression vector operably linked to or comprising a nucleic acid encoding the anti-BCMA CAR, and wherein the expression vector directs expression of the anti-BCMA CAR in the cell. In some embodiments, the present disclosure provides for the expression vector or the engineered cell, wherein the expression vector comprises a retroviral or lentiviral expression vector.[000201] Exemplary anti-BCMA CAR polypeptide and nucleic acid sequences are shown in Tables 1A and IB below.[000202] The anti-BCMA CARs described in Table 1A are schematically presented in Figure 1 (Benchmark construct numbering from FIG. 1 is noted in Table 1A). “Bivalent VH” described in Table 1A is used interchangeably herein with the phrase “bivalent VHH”and indicates two VH domains (e.g., “BCMA binder” described in FIG.l) connected via a linker. The antigen-binding regions of the BCMA binder described in Table 1 A and Fig. 1 are provided in Table IB and are also described in US Publication No. 2023 / 0257473.[000203] Table 1A. Exemplary Anti-BCMA CARsConstruct Antigen Hinge Transmembrane Costimulatory Activation Binding Domain (TM) Domain Domain Domain Domain1 BCMA CD8a CD8a 41BB CD3z Binder(monovalentVH)2 BCMA CD8a CD8a 41BB CD3z Binderbivalent VH3 BCMA CD8a CD8a 41BB CD3z Binderbivalent VH4 BCMA CD8a CD8a 41BB CD3z Binderbivalent VH5 BCMA CD8a CD8a 41BB CD3z Binderbivalent VH6 BCMA CD8a CD8a 41BB CD3z Binderbivalent VH7 BCMA CD8a CD28 CD28 CD3z Binderbivalent VH8 BCMA CD8a CD28 41BB CD3z Binderbivalent VH9 BCMA CD8a CD8a CD28 CD3z Binderbivalent VH10 BCMA CD8a CD8a CD28 CD3z BindermonovalentVHBenchmark BCMA CD8a CD8a 41BB CD3z 1 (1A) VHH1 / VHH2Benchmark C11D5. VL CD8a CD8a 41BB CD3z 2 (2A) / C11D5.3VHConstruct Antigen Hinge Transmembrane Costimulatory Activation Binding Domain (TM) Domain Domain Domain DomainBenchmark BCMA CD8a CD8a 41BB CD3z 3 (IB) VHH1 / VHH2Benchmark C11D5. VL CD8a CD8a 41BB CD3z 4 (2B) / C11D5.3VHTable IB. Exemplary Anti-BCMA CARsSEQ Construct Name SequenceID NO.1 CD8a signal ATGGCCCTGCCCGTGACCGCCCTGCTGCTGCCCCTGGCCCTGCTGC peptide DNA of TGCACGCCGCCCGGCCCConstruct 1,Construct 2,Construct 3,Construct 4,Construct 5,Construct 6,Construct 7,Construct 8,Construct 92 FR1 DNA (BCMA) CAGGTGCAGCTGGTGGAGAGCGGCGGCGGCCTGGTGCAGCCCGGCG of Construct GCAGCCTGCGGCTGAGCTGCGTGGCCAGC1, Construct2, Construct3, Construct4, Construct5, Construct6,Construct 7,Construct 8,Construct 93 CDR1 DNA GGCTTCACCTTCAGCAGCAACGCC(BCMA) ofConstruct 1,Construct 2,Construct 3,Construct 4,Construct 5,Construct 6,Construct 7,Construct 8,Construct 94 FR2 DNA (BCMA) ATGAGCTGGGTGCGGCAGGCCCCCGGCAAGGGCCTGGAGTGGGTGA of Construct GCGCC1, Construct2, Construct3, ConstructSEQ Construct Name SequenceID NO.4, Construct5, Construct6,Construct 7,Construct 8,Construct 95 CDR2 DNA ATCAGCGGCAGCGGCGACTACACC( BCMA) ofConstruct 1,Construct 2,Construct 3,Construct 4,Construct 5,Construct 6,Construct 7,Construct 8,Construct 96 FR3 DNA ( BCMA) CACTACAGCGACAGCGTGAAGGGCCGGTTCACCATCAGCCGGGACA of Construct ACAGCAAGAACACCCTGTACCTGCAGATGAACAGCCTGCGGGCCGA 1, Construct GGACACCGCCGTGTACTACTGC2, Construct3, Construct4, Construct5, Construct6,Construct 7,Construct 8,Construct 97 CDR3 DNA GCCAAGGAGGTGCCCGGCGGCCCCCTGGTGGACTTCGACAGC ( BCMA) ofConstruct 1,Construct 2,Construct 3,Construct 4,Construct 5,Construct 6,Construct 7,Construct 8,Construct 98 FR4 DNA ( BCMA) CGGGGCCAGGGCACCCTGGTGACCGTGAGCAGCof Construct1, Construct2, Construct3, Construct4, Construct5, Construct6,Construct 7,Construct 8,Construct 9SEQ Construct Name SequenceID NO.9 CD8a Hinge DNA ACCACCACCCCCGCCCCCCGGCCCCCCACCCCCGCCCCCACCATCG of Construct CCAGCCAGCCCCTGAGCCTGCGGCCCGAGGCCTGCCGGCCCGCCGC 1, Construct CGGCGGCGCCGTGCACACCCGGGGCCTGGACTTCGCCTGCGAC 2, Construct3, Construct4, Construct5, Construct6,Construct 7,Construct 8,Construct 910 TM ATCTACATCTGGGCCCCCCTGGCCGGCACCTGCGGCGTGCTGCTGC (Transmembrane TGAGCCTGGTGATCACCCTGTACTGC) DNA (CD8a)of Construct1, Construct2, Construct3, Construct4, Construct5, Construct6,Construct 911 ICD ( Internal AAGCGGGGCCGGAAGAAGCTGCTGTACATCTTCAAGCAGCCCTTCA Co stimulatory TGCGGCCCGTGCAGACCACCCAGGAGGAGGACGGCTGCAGCTGCCG Domain) DNA GTTCCCCGAGGAGGAGGAGGGCGGCTGCGAGCTG( 41BB) ofConstruct 1,Construct 2,Construct 3,Construct 4,Construct 5,Construct 6,Construct 812 CD3zeta DNA of CGGGTGAAGTTCAGCCGGAGCGCCGACGCCCCCGCCTACCAGCAGG Construct 1, GCCAGAACCAGCTGTACAACGAGCTGAACCTGGGCCGGCGGGAGGA Construct 2, GTACGACGTGCTGGACAAGCGGCGGGGCCGGGACCCCGAGATGGGC Construct 3, GGCAAGCCCCGGCGGAAGAACCCCCAGGAGGGCCTGTACAACGAGC Construct 4, TGCAGAAGGACAAGATGGCCGAGGCCTACAGCGAGATCGGCATGAA Construct 5, GGGCGAGCGGCGGCGGGGCAAGGGCCACGACGGCCTGTACCAGGGC Construct 6, CTGAGCACCGCCACCAAGGACACCTACGACGCCCTGCACATGCAGG Construct 7, CCCTGCCCCCCCGGConstruct 8,Construct 913 Stop codon DNA TAATGAof Construct1, Construct2, Construct3, Construct4, Construct5, Construct6,SEQ Construct Name SequenceID NO.Construct 7,Construct 8,Construct 9,Benchmark 1B,Benchmark 1A,Benchmark 2B,Benchmark 2A14 Linker DNA GGCGGCGGCGGCAGC(GGGGS ) ofConstruct 2,Construct 7,Construct 8,Construct 915 Linker DNA GGCGGCGGCGGCAGCGGCGGCGGCGGCAGC(GGGGS ) 2 ofConstruct 316 Linker DNA GGCGGCGGCGGCAGCGGCGGCGGCGGCAGCGGCGGCGGCGGCAGC (GGGGS ) 3 ofConstruct 417 Linker DNA GGCGGCGGCGGCAGCGGCGGCGGCGGCAGCGGCGGCGGCGGCAGCG (GGGGS ) 4 of GCGGCGGCGGCAGCConstruct 518 Linker DNA GGCGGCGGCGGCAGCGGCGGCGGCGGCAGCGGCGGCGGCGGCAGCG (GGGGS ) 5 of GCGGCGGCGGCAGCGGCGGCGGCGGCAGCConstruct 619 TM DNA (CD28 ) TTCTGGGTGCTGGTGGTGGTGGGCGGCGTGCTGGCCTGCTACAGCC of Construct TGCTGGTGACCGTGGCCTTCATCATCTTCTGGGTG7, Construct 820 ICD DNA (CD28 ) CGGAGCAAGCGGAGCCGGCTGCTGCACAGCGACTACATGAACATGA of Construct CCCCCCGGCGGCCCGGCCCCACCCGGAAGCACTACCAGCCCTACGC 7, Construct 9 CCCCCCCCGGGACTTCGCCGCCTACCGGAGC21 CD8a signal ATGGCTCTGCCCGTCACCGCTCTGCTGCTGCCTCTGGCTCTGCTGC peptide DNA of TGCACGCTGCTCGCCCTBenchmark 1B,Benchmark 1A22 VHH1 FR1 DNA CAGGT CAAACT GGAAGAAT CT GGCGGAGGCCTGGT GC AGGC AGGAC of Benchmark GGAGCCTGCGCCTGAGCTGCGCAGCATCCGAGCACACCTTCAGC IB, Benchmark1A23 VHH1 CDR1 DNA TCCCACGTGATGGGCof BenchmarkIB, Benchmark1A24 VHH1 FR2 DNA TGGTTTCGGCAGGCCCCAGGCAAGGAGAGAGAGAGCGTGGCC of BenchmarkIB, Benchmark1A25 VHH1 CDR2 DNA GTGATCGGCTGGAGGGACATCTCCACATCTTACGCCGATTCCGTGA of Benchmark AGGGCIB, Benchmark1ASEQ Construct Name SequenceID NO.26 VHH1 FR3 DNA CGGTTCACCATCAGCCGGGACAACGCCAAGAAGACACTGTATCTGC of Benchmark AGATGAACAGCCTGAAGCCCGAGGACACCGCCGTGTACTATTGCGC IB, Benchmark A1A27 VHH1 CDR3 DNA GC AAGGAGAAT CGACGC AGCAGACT TT GATT CCof BenchmarkIB, Benchmark1A28 VHH1 FR4 DNA TGGGGCCAGGGCACCCAGGTGACAGTGTCTAGCof BenchmarkIB, Benchmark1A29 Linker DNA of GGAGGAGGAGGATCTBenchmark 1B,Benchmark 1A30 VHH2 FR1 DNA GAGGTGCAGCTGGTGGAGAGCGGAGGCGGCCTGGTGCAGGCCGGAG of Benchmark GCTCTCTGAGGCTGAGCTGTGCAGCATCCGGAAGAIB, Benchmark1A31 VHH2 CDR1 DNA ACCTTCACAATGGGCof BenchmarkIB, Benchmark1A32 VHH2 FR2 DNA TGGTTTAGGCAGGCACCAGGAAAGGAGAGGGAGTTCGTGGCA of BenchmarkIB, Benchmark1A33 VHH2 CDR2 DNA GCAATCAGCCTGTCCCCTACCCTGGCCTACTATGCCGAGAGCGTGA of Benchmark AGGGCIB, Benchmark1A34 VHH2 FR3 DNA AGGTTTACCATCTCCCGCGATAACGCCAAGAATACAGTGGTGCTGC of Benchmark AGATGAACTCCCTGAAACCTGAGGACACAGCCCTGTACTATTGTGC IB, Benchmark C1A35 VHH2 CDR3 DNA GCCGATCGGAAGAGCGTGATGAGCATTAGACCAGACTATof BenchmarkIB, Benchmark1A36 VHH2 FR4 DNA TGGGGGCAGGGAACACAGGTGACCGTGAGCAGCof BenchmarkIB, Benchmark1A37 CD8a Hinge DNA ACCACGACGCCAGCGCCGCGACCACCAACACCGGCGCCCACCATCG of Benchmark CGTCGCAGCCCCTGTCCCTGCGCCCAGAGGCGTGCCGGCCAGCGGC IB, Benchmark GGGGGGCGCAGTGCACACGAGGGGGCTGGACTTCGCCTGTGAT 1A38 TM DNA (CD8a) ATCTACATCTGGGCGCCCTTGGCCGGGACTTGTGGGGTCCTTCTCC of Benchmark TGTCACTGGTTATCACCCTTTACTGCIB, Benchmark1ASEQ Construct Name SequenceID NO.39 ICD DNA ( 4 IBB) AAACGGGGCAGAAAGAAACTCCTGTATATATTCAAACAACCATTTA of Benchmark TGAGACCAGTACAAACTACTCAAGAGGAAGATGGCTGTAGCTGCCG IB, Benchmark ATTTCCAGAAGAAGAAGAAGGAGGATGTGAACTG1A40 CD3zeta DNA of AGAGTGAAGTTCAGCAGGAGCGCAGACGCCCCCGCGTACCAGCAGG Benchmark 1B, GCCAGAACCAGCTCTATAACGAGCTCAATCTAGGACGAAGAGAGGA Benchmark 1A GTACGATGTTTTGGACAAGAGACGTGGCCGGGACCCTGAGATGGGG GGAAAGCCGAGAAGGAAGAACCCTCAGGAAGGCCTGTACAATGAAC TGCAGAAAGATAAGATGGCGGAGGCCTACAGTGAGATTGGGATGAA AGGCGAGCGCCGGAGGGGCAAGGGGCACGATGGCCTTTACCAGGGT CTCAGTACAGCCACCAAGGACACCTACGACGCCCTTCACATGCAGG CCCTGCCCCCTCGC41 CD8a signal ATGGCACTCCCCGTCACCGCCCTTCTCTTGCCCCTCGCCCTGCTGC peptide DNA of TGCATGCTGCCAGGCCCBenchmark 2B,Benchmark 2A42 VL FR1 DNA of GACATTGTGCTCACTCAGTCACCTCCCAGCCTGGCCATGAGCCTGG Benchmark 2B, GAAAAAGGGCCACCATCTCCTGTBenchmark 2A43 VL CDR1 DNA of AGAGCCAGTGAGTCCGTCACAATCTTGGGGAGCCATCTTATTCAC Benchmark 2B,Benchmark 2A44 VL FR2 DNA of TGGTATCAGCAGAAGCCCGGGCAGCCTCCAACCCTTCTTATTCAG Benchmark 2B,Benchmark 2A45 VL CDR2 DNA of CTCGCGTCAAACGTCCAGACGBenchmark 2B,Benchmark 2A46 VL FR3 DNA of GGTGTACCTGCCAGATTTTCTGGTAGCGGGTCCCGCACTGATTTTA Benchmark 2B, CACTGACCATAGATCCAGTGGAAGAAGACGATGTGGCCGTGTATTA Benchmark 2A TTGT47 VL CDR3 DNA of CTGCAGAGCAGAACGATTCCTCGCACABenchmark 2B,Benchmark 2A48 VL FR4 DNA of TTTGGTGGGGGTACTAAGCTGGAGATTAAGBenchmark 2B,Benchmark 2A49 Linker DNA of GGAAGCACGTCCGGCTCAGGGAAGCCGGGCTCCGGCGAGGGAAGCA Benchmark 2B, CGAAGGGGBenchmark 2A50 VH FR1 DNA of CAAATTCAGCTGGTCCAGAGCGGACCTGAGCTGAAAAAACCCGGCG Benchmark 2B, AGACTGTTAAGATCAGTTGTAAAGCATCTGGCTATACCTTCACC Benchmark 2A51 VH CDR1 DNA of GACTACAGCATAAATBenchmark 2B,Benchmark 2A52 VH FR2 DNA of TGGGTGAAACGGGCCCCTGGAAAGGGCCTCAAATGGATGGGT Benchmark 2B,Benchmark 2A53 VH CDR2 DNA of TGGATCAATACCGAAACTAGGGAGCCTGCTTATGCATATGACTTCC Benchmark 2B, GCGGGBenchmark 2ASEQ Construct Name SequenceID NO.54 VH FR3 DNA of AGATTCGCCTTTTCACTCGAGACATCTGCCTCTACTGCTTACCTCC Benchmark 2B, AAATAAACAACCTCAAGTATGAAGATACAGCCACTTACTTTTGCGC Benchmark 2A CCTC55 VH CDR3 DNA of GACTATAGTTACGCCATGGACTACBenchmark 2B,Benchmark 2A56 VH FR4 DNA of TGGGGACAGGGAACCTCCGTTACCGTCAGTTCC Benchmark 2B,Benchmark 2A57 CD8a Hinge DNA GCGGCCGCAACCACAACACCTGCTCCAAGGCCCCCCACACCCGCTC of Benchmark CAACTATAGCCAGCCAACCATTGAGCCTCAGACCTGAAGCTTGCAG 2B, Benchmark GCCCGCAGCAGGAGGCGCCGTCCATACGCGAGGCCTGGACTTCGCG 2A TGTGAT58 TM DNA (CD8a) ATTTATATTTGGGCCCCTTTGGCCGGAACATGTGGGGTGTTGCTTC of Benchmark TCTCCCTTGTGATCACTCTGTATTGT2B, Benchmark2A59 ICD DNA ( 4 IBB) AAGCGCGGGAGAAAGAAGCTCCTGTACATCTTCAAGCAGCCTTTTA of Benchmark TGCGACCTGTGCAAACCACTCAGGAAGAAGATGGGTGTTCATGCCG 2B, Benchmark CTTCCCCGAGGAGGAAGAAGGAGGGTGTGAACTG2A60 CD3zeta DNA of AGGGTGAAATTTTCTAGAAGCGCCGATGCTCCCGCATATCAGCAGG Benchmark 2B, GTCAGAATCAGCTCTACAATGAATTGAATCTCGGCAGGCGAGAAGA Benchmark 2A GTACGATGTTCTGGACAAGAGACGGGGCAGGGATCCCGAGATGGGG GGAAAGCCCCGGAGAAAAAATCCTCAGGAGGGGTTGTACAATGAGC TGCAGAAGGACAAGATGGCTGAAGCCTATAGCGAGATCGGAATGAA AGGCGAAAGACGCAGAGGCAAGGGGCATGACGGTCTGTACCAGGGT CTCTCTACAGCCACCAAGGACACTTATGATGCGTTGCATATGCAAG CCTTGCCACCCCGC61 CD8a signal MALPVTALLLPLALLLHAARPpeptide aa ofConstruct 1,Construct 2,Construct 3,Construct 4,Construct 5,Construct 6,Construct 7,Construct 8,Construct 9,Benchmark 1B,Benchmark 1A,Benchmark 2B,Benchmark 2A62 FR1 aa (BCMA) QVQLVESGGGLVQPGGSLRLSCVASof Construct1, Construct2, Construct3, Construct4, Construct5, Construct6,SEQ Construct Name SequenceID NO.Construct 7,Construct 8,Construct 963 CDR1 aa ( BCMA) GFTFSSNAof Construct1, Construct2, Construct3, Construct4, Construct5, Construct6,Construct 7,Construct 8,Construct 964 FR2 aa ( BCMA) MSWVRQAPGKGLEWVSAof Construct1, Construct2, Construct3, Construct4, Construct5, Construct6,Construct 7,Construct 8,Construct 965 CDR2 aa ( BCMA) ISGSGDYTof Construct1, Construct2, Construct3, Construct4, Construct5, Construct6,Construct 7,Construct 8,Construct 966 FR3 aa ( BCMA) HYSDSVKGRFT ISRDNSKNTLYLQMNSLRAEDTAVYYC of Construct1, Construct2, Construct3, Construct4, Construct5, Construct6,Construct 7,Construct 8,Construct 967 CDR3 aa ( BCMA) AKEVPGGPLVDFDSof Construct1, Construct2, Construct3, ConstructSEQ Construct Name SequenceID NO.4, Construct5, Construct6,Construct 7,Construct 8,Construct 968 FR4 aa ( BCMA) RGQGTLVTVSSof Construct1, Construct2, Construct3, Construct4, Construct5, Construct6,Construct 7,Construct 8,Construct 969 CD8a Hinge aa TTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACD of Construct1, Construct2, Construct3, Construct4, Construct5, Construct6,Construct 7,Construct 8,Construct 9,Benchmark 1A,Benchmark 1B70 TM aa ( CD8 a ) I Y IWAPLAGTCGVLLLSLVITLYCof Construct1, Construct2, Construct3, Construct4, Construct5, Construct6,Construct 9,Benchmark 1B,Benchmark 1A,Benchmark 2B,Benchmark 2A71 ICD aa ( 41BB ) KRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCEL of Construct1, Construct2, Construct3, Construct4, Construct5, Construct6,SEQ Construct Name SequenceID NO.Construct 8,Benchmark 1B,Benchmark 1A,Benchmark 2B,Benchmark 2A72 CD3zeta aa of RVKFSRSADAPAYQQGQNQLYNELNLGRREEYDVLDKRRGRDPEMG Construct 1, GKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQG Construct 2, LSTATKDTYDALHMQALPPRConstruct 3,Construct 4,Construct 5,Construct 6,Construct 7,Construct 8,Construct 9,Benchmark 1B,Benchmark 1A,Benchmark 2B,Benchmark 2A73 Linker aa GGGGS(GGGGS ) ofConstruct 2,Construct 7,Construct 8,Construct 9,Benchmark 1B,Benchmark 1A74 Linker aa GGGGSGGGGS(GGGGS ) 2 ofConstruct 375 Linker aa GGGGSGGGGSGGGGS(GGGGS ) 3 ofConstruct 476 Linker aa GGGGSGGGGSGGGGSGGGGS(GGGGS ) 4 ofConstruct 577 Linker aa GGGGSGGGGSGGGGSGGGGSGGGGS(GGGGS ) 5 ofConstruct 678 TM aa (CD28 ) FWVLVVVGGVLACYSLLVTVAFIIFWVof Construct7, Construct 879 ICD aa (CD28 ) RSKRSRLLHSDYMNMTPRRPGPTRKHYQPYAPPRDFAAYRS of Construct7, Construct 980 Monovalent VHH CAGGTGCAGCTGGTGGAGAGCGGCGGCGGCCTGGTGCAGCCCGGCG BCMA CAR GCAGCCTGCGGCTGAGCTGCGTGGCCAGCGGCTTCACCTTCAGCAGConstruct 2 CAACGCCATGAGCTGGGTGCGGCAGGCCCCCGGCAAGGGCCTGGAG DNA TGGGTGAGCGCCATCAGCGGCAGCGGCGACTACACCCACTACAGCG ACAGCGTGAAGGGCCGGTTCACCATCAGCCGGGACAACAGCAAGAACACCCTGTACCTGCAGATGAACAGCCTGCGGGCCGAGGACACCGCCSEQ Construct Name SequenceID NO.GTGTACTACTGCGCCAAGGAGGTGCCCGGCGGCCCCCTGGTGGACT TCGACAGCCGGGGCCAGGGCACCCTGGTGACCGTGAGCAGC81 Monovalent VHH QVQLVESGGGLVQPGGSLRLSCVASGFTFSSNAMSWVRQAPGKGLE BCMA CAR WVSAISGSGDYTHYSDSVKGRFTISRDNSKNTLYLQMNSLRAEDTAConstruct 2 aa VYYCAKEVPGGPLVDFDSRGQGTLVTVSS82 BCMA Lead CAR ATGGCCCTGCCCGTGACCGCCCTGCTGCTGCCCCTGGCCCTGCTGC Construct 2 TGCACGCCGCCCGGCCCCAGGTGCAGCTGGTGGAGAGCGGCGGCGG DNA Full CCTGGTGCAGCCCGGCGGCAGCCTGCGGCTGAGCTGCGTGGCCAGC (signal GGCTTCACCTTCAGCAGCAACGCCATGAGCTGGGTGCGGCAGGCCC sequence CCGGCAAGGGCCTGGAGTGGGTGAGCGCCATCAGCGGCAGCGGCGA underlined) CTACACCCACTACAGCGACAGCGTGAAGGGCCGGTTCACCATCAGC CGGGACAACAGCAAGAACACCCTGTACCTGCAGATGAACAGCCTGC GGGCCGAGGACACCGCCGTGTACTACTGCGCCAAGGAGGTGCCCGG CGGCCCCCTGGTGGACTTCGACAGCCGGGGCCAGGGCACCCTGGTG ACCGTGAGCAGCGGCGGCGGCGGCAGCCAGGTGCAGCTGGTGGAGA GCGGCGGCGGCCTGGTGCAGCCCGGCGGCAGCCTGCGGCTGAGCTG CGTGGCCAGCGGCTTCACCTTCAGCAGCAACGCCATGAGCTGGGTG CGGCAGGCCCCCGGCAAGGGCCTGGAGTGGGTGAGCGCCATCAGCG GCAGCGGCGACTACACCCACTACAGCGACAGCGTGAAGGGCCGGTT CACCATCAGCCGGGACAACAGCAAGAACACCCTGTACCTGCAGATG AACAGCCTGCGGGCCGAGGACACCGCCGTGTACTACTGCGCCAAGG AGGTGCCCGGCGGCCCCCTGGTGGACTTCGACAGCCGGGGCCAGGG CACCCTGGTGACCGTGAGCAGCACCACCACCCCCGCCCCCCGGCCC CCCACCCCCGCCCCCACCATCGCCAGCCAGCCCCTGAGCCTGCGGC CCGAGGCCTGCCGGCCCGCCGCCGGCGGCGCCGTGCACACCCGGGG CCTGGACTTCGCCTGCGACATCTACATCTGGGCCCCCCTGGCCGGC ACCTGCGGCGTGCTGCTGCTGAGCCTGGTGATCACCCTGTACTGCA AGCGGGGCCGGAAGAAGCTGCTGTACATCTTCAAGCAGCCCTTCAT GCGGCCCGTGCAGACCACCCAGGAGGAGGACGGCTGCAGCTGCCGG TTCCCCGAGGAGGAGGAGGGCGGCTGCGAGCTGCGGGTGAAGTTCA GCCGGAGCGCCGACGCCCCCGCCTACCAGCAGGGCCAGAACCAGCT GTACAACGAGCTGAACCTGGGCCGGCGGGAGGAGTACGACGTGCTG GACAAGCGGCGGGGCCGGGACCCCGAGATGGGCGGCAAGCCCCGGC GGAAGAACCCCCAGGAGGGCCTGTACAACGAGCTGCAGAAGGACAA GATGGCCGAGGCCTACAGCGAGATCGGCATGAAGGGCGAGCGGCGG CGGGGCAAGGGCCACGACGGCCTGTACCAGGGCCTGAGCACCGCCA CCAAGGACACCTACGACGCCCTGCACATGCAGGCCCTGCCCCCCCG GTAATGA83 BCMA Lead CAR QVQLVESGGGLVQPGGSLRLSCVASGFTFSSNAMSWVRQAPGKGLE Construct 2 WVSAISGSGDYTHYSDSVKGRFTISRDNSKNTLYLQMNSLRAEDTA Protein Full VYYCAKEVPGGPLVDFDSRGQGTLVTVSSGGGGSQVQLVESGGGLV QPGGSLRLSCVASGFTFSSNAMSWVRQAPGKGLEWVSAISGSGDYT HYSDSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKEVPGGP LVDFDSRGQGTLVTVSSTTTPAPRPPTPAPTIASQPLSLRPEACRP AAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKK LLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRSADA PAYQQGQNQLYNELNLGRREEYDVLDKRRGRDPEMGGKPRRKNPQE GLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYD ALHMQALPPR84 BCMA Construct QVQLVESGGGLVQPGGSLRLSCVASGFTFSSNAMSWVRQAPGKGLE 2 Bivalent VHH WVSAISGSGDYTHYSDSVKGRFTISRDNSKNTLYLQMNSLRAEDTA(linker in VYYCAKEVPGGPLVDFDSRGQGTLVTVSSGGGGSQVQLVESGGGLVSEQ Construct Name SequenceID NO.italics and QPGGSLRLSCVASGFTFSSNAMSWVRQAPGKGLEWVSAISGSGDYT underlined) HYSDSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKEVPGGP LVDFDSRGQGTLVTVSS85 Exemplary CD8a ACTACGACGCCCGCCCCGAGGCCCCCTACCCCCGCACCAACCATTG Hinge ORF CGTCCCAGCCGTTGAGCCTGCGGCCTGAAGCTTGCCGACCGGCAGC GGGTGGCGCCGTCCACACTCGCGGTTTGGATTTCGCTTGTGAC86 Exemplary CD8a accaccacccctgcccctagacctcccaccccagccccaacaatcg Hinge ORF ccagccagcctctgtctctgcggcccgaagcctgtagacctgctgc cggcggagccgtgcacaccagaggcctggacttcgcctgcgac 87 Exemplary CD8a ACGACCACACCGGCTCCTAGGCCACCCACCCCGGCGCCAACCATCG Hinge ORF CATCCCAGCCTTTGAGTCTGCGTCCCGAGGCCTGTCGTCCCGCGGC TGGGGGCGCCGTCCACACCCGTGGTTTGGATTTCGCCTGCGAC88 Exemplary CD8a ACCACAACCCCGGCTCCACGCCCCCCCACGCCCGCGCCTACCATCG Hinge ORF CCAGCCAGCCACTCTCTCTGCGCCCTGAGGCTTGCCGACCGGCCGC TGGGGGGGCGGTGCACACGCGCGGTTTGGATTTCGCGTGCGAC89 CD8a Hinge AA TTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACD sequence90 Exemplary CD28 TTCTGGGTACTTGTTGTGGTGGGGGGCGTATTAGCATGCTACTCCC TM ORF TTCTGGTTACCGTCGCGTTCATCATCTTCTGGGTC91 Exemplary CD28 TTTTGGGTCCTGGTCGTGGTGGGCGGCGTCCTTGCTTGTTACTCCC TM ORF TACTCGTCACCGTGGCGTTCATCATCTTCTGGGTC92 Exemplary CD28 TTTTGGGTGCTCGTTGTGGTGGGCGGTGTGCTTGCGTGCTACTCAC TM ORF TTCTGGTGACTGTTGCGTTCATCATCTTCTGGGTC93 CD28 TM AA FWVLVVVGGVLACYSLLVTVAFIIFWVsequence94 Exemplary CD8a atctacatctgggcccctctggccggcacctgtggcgtgctgctgc TM ORF tgagcctggtgatcaccctgtactgc95 CD8a TM AA I Y IWAPLAGTCGVLLLSLVITLYCsequence96 Exemplary CD28 AGGTCGAAGCGCAGCCGCCTGCTCCATAGCGACTACATGAATATGA Costim ORF CCCCCCGTCGGCCTGGCCCCACACGCAAGCACTACCAGCCCTACGC CCCCCCAAGAGACTTCGCGGCCTAC97 Exemplary CD28 CGTAGCAAGCGCAGCAGGCTGCTGCACTCCGATTACATGAACATGA Costim ORF CTCCGCGCCGCCCCGGTCCGACCCGCAAGCACTACCAGCCCTATGC ACCGCCCAGGGACTTTGCTGCCTAC98 Exemplary CD28 CGCTCTAAGCGCAGCCGCCTGCTGCACAGCGATTACATGAATATGA Costim ORF CTCCGCGCCGCCCTGGCCCTACCCGCAAGCACTACCAGCCCTATGC TCCCCCCCGGGACTTTGCAGCCTAC99 CD28 Costim AA RSKRSRLLHSDYMNMTPRRPGPTRKHYQPYAPPRDFAAY sequence100 Exemplary 41BB aaacggggcagaaagaaactcctgtatatattcaaacaaccattta Costim ORF tgagaccagtacaaactactcaagaggaagatggctgtagctgccg atttccagaagaagaagaaggaggatgtgaactg101 BCMA Lead CAR MALPVTALLLPLALLLHAARPQVQLVESGGGLVQPGGSLRLSCVAS Construct 2 GFTFSSNAMSWVRQAPGKGLEWVSAISGSGDYTHYSDSVKGRFTIS Protein Full RDNSKNTLYLQMNSLRAEDTAVYYCAKEVPGGPLVDFDSRGQGTLV including TVSSGGGGSQVQLVESGGGLVQPGGSLRLSCVASGFTFSSNAMSWV signal peptide RQAPGKGLEWVSAISGSGDYTHYSDSVKGRFTISRDNSKNTLYLQM (signal NSLRAEDTAVYYCAKEVPGGPLVDFDSRGQGTLVTVSSTTTPAPRP sequence is PTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAG underlined) TCGVLLLSLVITLYCKRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYQQGQNQLYNELNLGRREEYDVLSEQ Construct Name SequenceID NO.DKRRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERR RGKGHDGLYQGLSTATKDTYDALHMQALPPR102 Exemplary CD3 CGCGTGAAGTTTTCACGCTCTGCGGACGCTCCCGCTTATCAGCAGG Zeta ORF GCCAGAACCAGCTTTACAACGAGCTTAACCTGGGCCGCCGAGAGGA GTACGATGTGCTGGACAAGCGCAGGGGCCGTGACCCGGAGATGGGC GGGAAGCCTCAGCGCCGCAAAAACCCACAGGAGGGCCTGTACAACG AGCTGCAGAAGGACAAAATGGCCGAGGCCTACTCCGAGATAGGTAT GAAGGGCGAGCGCCGGCGTGGTAAAGGCCACGATGGCCTCTATCAG GGTCTGTCCACCGCCACCAAGGACACCTACGACGCACTGCATATGC AAGCGTTACCACCCCGC103 CD3 Zeta AA RVKFSRSADAPAYQQGQNQLYNELNLGRREEYDVLDKRRGRDPEMG sequence GKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQG LSTATKDTYDALHMQALPPR104 Exemplary CD3 AGAGTGAAGTTCAGCAGATCCGCCGACGCCCCTGCCTACCAGCAGG Zeta ORF GACAGAACCAGCTGTACAACGAGCTGAACCTGGGCAGACGGGAAGA GTACGACGTGCTGGACAAGCGGAGAGGCCGGGACCCCGAGATGGGC GGAAAGCCCAGACGGAAGAACCCCCAGGAAGGCCTGTATAACGAAC TGCAGAAAGACAAGATGGCCGAGGCCTACAGCGAGATCGGCATGAA GGGCGAGCGGAGGCGCGGCAAGGGCCACGATGGCCTGTACCAGGGC CTGAGCACCGCCACCAAGGACACCTACGACGCCCTGCACATGCAGG CCCTGCCCCCCAGA105 - - 106 (AAV2-5ITR | taatcagaattggttaattggttgtaacattattcagattgggctt LHA | EFla | gatttaaaacttcatttttaatttaaaaggatctaggtgaagatcc CD8a leader tttttgataatctcatgaccaaaatcccttaacgtgagttttcgtt sequence | CD8a ccactgagcgtcagaccccgtagaaaagatcaaaggatcttcttga hingeTM-41BB- gatcctttttttctgcgcgtaatctgctgcttgcaaacaaaaaaac CD3z | bGH PA caccgctaccagcggtggtttgtttgccggatcaagagctaccaac terminator | tctttttccgaaggtaactggcttcagcagagcgcagataccaaat RHA | AAV2 - actgttcttctagtgtagccgtagttaggccaccacttcaagaact 5ITR) ctgtagcaccgcctacatacctcgctctgctaatcctgttaccagt ggctgctgccagtggcgataagtcgtgtcttaccgggttggactca agacgatagttaccggataaggcgcagcggtcgggctgaacggggg Full AAV gttcgtgcacacagcccagcttggagcgaacgacctacaccgaact plasmid gagatacctacagcgtgagctatgagaaagcgccacgcttcccgaa sequence; gggagaaaggcggacaggtatccggtaagcggcagggtcggaacag capitalized gagagcgcacgagggagcttccagggggaaacgcctggtatcttta sequence tagtcctgtcgggtttcgccacctctgacttgagcgtcgatttttg represents tgatgctcgtcaggggggcggagcctatggaaaaacgccagcaacg portion cggcctttttacggttcctggccttttgctggccttttgctcacat integrated gttctttcctgcgttatcccctgattctgtggataaccgtattacc into cell gcctttgagtgagctgataccgctcgccgcagccgaacgaccgagc genome; gcagcgagtcagtgagcgaggaagcggaagagcgcccaatacgcaa underlined accgcctctccccgcgcgttggccgattcattaatgcagctggcac portion gacaggtttcccgactggaaagcgggcagtgagcgcaacgcaatta represents SEQ atgtgagttagctcactcattaggcaccccaggctttacactttat ID NO: 82 gcttccggctcgtatgttgtgtggaattgtgagcggataacaattt cacacaggaaacagctatgaccatgattacaccacgcgtttggcca ctccctctctgcgcgctcgctcgctcactgaggccgggcgaccaaa ggtcgcccgacgcccgggctttgcccgggcggcctcagt gagcgag cgagcgcgcagagagggagtggccaactccatcactaggggttcctagatcttgccaacataccataaacctcccattctgctaatgcccagSEQ Construct Name SequenceID NO.cctaagttggggagaccactccagattccaagatgtacagtttgct ttgctgggcctttttcccatgcctgcctttactctgccagagttat attgctggggttttgaagaagatcctattaaataaaagaataagca gtattattaagtagccctgcatttcaggtttccttgagtggcaggc caggcctggccgtgaacgttcactgaaatcatggcctcttggccaa gattgatagcttgtgcctgtccctgagtcccagtccatcacgagca gctggtttctaagatgctatttcccgtataaagcatgagaccgtga cttgccagccccacagagccccgcccttgtccatcactggcatctg gactccagcctgggttggggcaaagagggaaatgagatcatgtcct aaccctgatcctcttgtcccacagatatccagaaccctgaccctgc GGCTCCGGTGCCCGTCAGTGGGCAGAGCGCACATCGCCCACAGTCC CCGAGAAGTTGGGGGGAGGGGTCGGCAATTGAACCGGTGCCTAGAG AAGGTGGCGCGGGGTAAACTGGGAAAGTGATGTCGTGTACTGGCTC CGCCTTTTTCCCGAGGGTGGGGGAGAACCGTATATAAGTGCAGTAG TCGCCGTGAACGTTCTTTTTCGCAACGGGTTTGCCGCCAGAACACA GGTAAGTGCCGTGTGTGGTTCCCGCGGGCCTGGCCTCTTTACGGGT TATGGCCCTTGCGTGCCTTGAATTACTTCCACGCCCCTGGCTGCAG TACGTGATTCTTGATCCCGAGCTTCGGGTTGGAAGTGGGTGGGAGA GTTCGAGGCCTTGCGCTTAAGGAGCCCCTTCGCCTCGTGCTTGAGT TGAGGCCTGGCTTGGGCGCTGGGGCCGCCGCGTGCGAATCTGGTGG CACCTTCGCGCCTGTCTCGCTGCTTTCGATAAGTCTCTAGCCATTT AAAATTTTTGATGACCTGCTGCGACGCTTTTTTTCTGGCAAGATAG TCTTGTAAATGCGGGCCAAGATGTGCACACTGGTATTTCGGTTTTT GGGGCCGCGGGCGGCGACGGGGCCCGTGCGTCCCAGCGCACATGTT CGGCGAGGCGGGGCCTGCGAGCGCGGCCACCGAGAATCGGACGGGG GTAGTCTCAAGCTGGCCGGCCTGCTCTGGTGCCTGGCCTCGCGCCG CCGTGTATCGCCCCGCCCTGGGCGGCAAGGCTGGCCCGGTCGGCAC CAGTTGCGTGAGCGGAAAGATGGCCGCTTCCCGGCCCTGCTGCAGG GAGCTCAAAATGGAGGACGCGGCGCTCGGGAGAGCGGGCGGGTGAG TCACCCACACAAAGGAAAAGGGCCTTTCCGTCCTCAGCCGTCGCTT CATGTGACTCCACGGAGTACCGGGCGCCGTCCAGGCACCTCGATTA GTTCTCGAGCTTTTGGAGTACGTCGTCTTTAGGTTGGGGGGAGGGG TTTTATGCGATGGAGTTTCCCCACACTGAGTGGGTGGAGACTGAAG TTAGGCCAGCTTGGCACTTGATGTAATTCTCCTTGGAATTTGCCCT TTTTGAGTTTGGATCTTGGTTCATTCTCAAGCCTCAGACAGTGGTT CAAAGTTTTTTTCTTCCATTTCAGGTGTCGTGATGCGGCCGCCACC ATGGCCCTGCCCGTGACCGCCCTGCTGCTGCCCCTGGCCCTGCTGC TGCACGCCGCCCGGCCCCAGGTGCAGCTGGTGGAGAGCGGCGGCGG CCTGGTGCAGCCCGGCGGCAGCCTGCGGCTGAGCTGCGTGGCCAGC GGCTTCACCTTCAGCAGCAACGCCATGAGCTGGGTGCGGCAGGCCC CCGGCAAGGGCCTGGAGTGGGTGAGCGCCATCAGCGGCAGCGGCGA CTACACCCACTACAGCGACAGCGTGAAGGGCCGGTTCACCATCAGC CGGGACAACAGCAAGAACACCCTGTACCTGCAGATGAACAGCCTGC GGGCCGAGGACACCGCCGTGTACTACTGCGCCAAGGAGGTGCCCGG CGGCCCCCTGGTGGACTTCGACAGCCGGGGCCAGGGCACCCTGGTG ACCGTGAGCAGCGGCGGCGGCGGCAGCCAGGTGCAGCTGGTGGAGA GCGGCGGCGGCCTGGTGCAGCCCGGCGGCAGCCTGCGGCTGAGCTG CGTGGCCAGCGGCTTCACCTTCAGCAGCAACGCCATGAGCTGGGTG CGGCAGGCCCCCGGCAAGGGCCTGGAGTGGGTGAGCGCCATCAGCG GCAGCGGCGACTACACCCACTACAGCGACAGCGTGAAGGGCCGGTT CACCATCAGCCGGGACAACAGCAAGAACACCCTGTACCTGCAGATGAACAGCCTGCGGGCCGAGGACACCGCCGTGTACTACTGCGCCAAGGSEQ Construct Name SequenceID NO.AGGTGCCCGGCGGCCCCCTGGTGGACTTCGACAGCCGGGGCCAGGG CACCCTGGTGACCGTGAGCAGCACCACCACCCCCGCCCCCCGGCCC CCCACCCCCGCCCCCACCATCGCCAGCCAGCCCCTGAGCCTGCGGC CCGAGGCCTGCCGGCCCGCCGCCGGCGGCGCCGTGCACACCCGGGG CCTGGACTTCGCCTGCGACATCTACATCTGGGCCCCCCTGGCCGGC ACCTGCGGCGTGCTGCTGCTGAGCCTGGTGATCACCCTGTACTGCA AGCGGGGCCGGAAGAAGCTGCTGTACATCTTCAAGCAGCCCTTCAT GCGGCCCGTGCAGACCACCCAGGAGGAGGACGGCTGCAGCTGCCGG TTCCCCGAGGAGGAGGAGGGCGGCTGCGAGCTGCGGGTGAAGTTCA GCCGGAGCGCCGACGCCCCCGCCTACCAGCAGGGCCAGAACCAGCT GTACAACGAGCTGAACCTGGGCCGGCGGGAGGAGTACGACGTGCTG GACAAGCGGCGGGGCCGGGACCCCGAGATGGGCGGCAAGCCCCGGC GGAAGAACCCCCAGGAGGGCCTGTACAACGAGCTGCAGAAGGACAA GATGGCCGAGGCCTACAGCGAGATCGGCATGAAGGGCGAGCGGCGG CGGGGCAAGGGCCACGACGGCCTGTACCAGGGCCTGAGCACCGCCA CCAAGGACACCTACGACGCCCTGCACATGCAGGCCCTGCCCCCCCG GTAATGACCTCGACTGTGCCTTCTAGTTGCCAGCCATCTGTTGTTT GCCCCTCCCCCGTGCCTTCCTTGACCCTGGAAGGTGCCACTCCCAC TGTCCTTTCCTAATAAAATGAGGAAATTGCATCGCATTGTCTGAGT AGGTGTCATTCTATTCTGGGGGGTGGGGTGGGGCAGGACAGCAAGG GGGAGGATTGGGAAGACAATAGCAGGCATGCTGGGGATGCGGTGGG CTCTATGGCTTCTGAGGCGGAAAGAACCAGCTGGGGCTCTAGGGGG TATCCCCACTAGTcgtgtaccagctgagagactctaaatccagtga caagtctgtctgcctattcaccgattttgattctcaaacaaatgtg tcacaaagtaaggattctgatgtgtatatcacagacaaaactgtgc tagacatgaggtctatggacttcaagagcaacagtgctgtggcctg gagcaacaaatctgactttgcatgtgcaaacgccttcaacaacagc attattccagaagacaccttcttccccagcccaggtaagggcagct ttggtgccttcgcaggctgtttccttgcttcaggaatggccaggtt ctgcccagagctctggtcaatgatgtctaaaactcctctgattggt ggtctcggccttatccattgccaccaaaaccctctttttactaaga aacagtgagccttgttctggcagtccagagaatgacacgggaaaaa agcagatgaagagaaggtggcaggagagggcacgtggcc cagctccagtctctagatctaggaacccctagtgatggagttggccactccct ctctgcgcgctcgctcgctcactgaggccgcccgggcaaagcccgg gcgtcgggcgacctttggtcgcccggcctcagtgagcgagcgagcg cgcagagagggagtggccaagaattctctggccgtcgttttacaac gtcgtgactgggaaaaccctggcgttacccaacttaatcgccttgc agcacatccccctttcgccagctggcgtaatagcgaagaggcccgc accgatcgcccttcccaacagttgcgcagcctgaatggcgaatggc gcctgatgcggtattttctccttacgcatctgtgcggtatttcaca ccgcatatggtgcactctcagtacaatctgctctgatgccgcatag ttaagccagccccgacacccgccaacacccgctgacgcgccctgac gggcttgtctgctcccggcatccgcttacagacaagctgtgaccgt ctccgggagctgcatgtgtcagaggttttcaccgtcatcaccgaaa cgcgcgatgcagctctggcccgtgtctcaaaatctctgatgttaca ttgcacaagataaaaatatatcatcatgaacaataaaactgtctgc ttacataaacagtaatacaaggggtgttatgagccatattcaacgg gaaacgtcgaggccgcgattaaattccaacatggatgctgatttat atgggtataaatgggctcgcgataatgtcgggcaatcaggtgcgac aatctatcgcttgtatgggaagcccgatgcgccagagttgtttctgaaacatggcaaaggtagcgttgccaatgatgttacagatgagatggSEQ Construct Name SequenceID NO.tcagactaaactggctgacggaatttatgcctcttccgaccatcaa gcattttatccgtactcctgatgatgcatggttactcaccactgcg atccccggaaaaacagcattccaggtattagaagaatatcctgatt caggtgaaaatattgttgatgcgctggcagtgttcctgcgccggtt gcattcgattcctgtttgtaattgtccttttaacagcgatcgcgta tttcgtctcgctcaggcgcaatcacgaatgaataacggtttggttg atgcgagtgattttgatgacgagcgtaatggctggcctgttgaaca agtctggaaagaaatgcataaacttttgccattctcaccggattca gtcgtcactcatggtgatttctcacttgataaccttatttttgacg aggggaaattaataggttgtattgatgttggacgagtcggaatcgc agaccgataccaggatcttgccatcctatggaactgcctcggtgag ttttctccttcattacagaaacggctttttcaaaaatatggtattg ataatcctgatatgaataaattgcagtttcatttgatgctcgatga gtttttc107 Genome GGCTCCGGTGCCCGTCAGTGGGCAGAGCGCACATCGCCCACAGTCC integration CCGAGAAGTTGGGGGGAGGGGTCGGCAATTGAACCGGTGCCTAGAG sequence, AAGGTGGCGCGGGGTAAACTGGGAAAGTGATGTCGTGTACTGGCTC including CGCCTTTTTCCCGAGGGTGGGGGAGAACCGTATATAAGTGCAGTAG anti-BCMA CAR TCGCCGTGAACGTTCTTTTTCGCAACGGGTTTGCCGCCAGAACACA sequence GGTAAGTGCCGTGTGTGGTTCCCGCGGGCCTGGCCTCTTTACGGGT TATGGCCCTTGCGTGCCTTGAATTACTTCCACGCCCCTGGCTGCAGSequence which TACGTGATTCTTGATCCCGAGCTTCGGGTTGGAAGTGGGTGGGAGA is capitalized GTTCGAGGCCTTGCGCTTAAGGAGCCCCTTCGCCTCGTGCTTGAGT in SEQ ID NO: TGAGGCCTGGCTTGGGCGCTGGGGCCGCCGCGTGCGAATCTGGTGG 106. CACCTTCGCGCCTGTCTCGCTGCTTTCGATAAGTCTCTAGCCATTT AAAATTTTTGATGACCTGCTGCGACGCTTTTTTTCTGGCAAGATAG TCTTGTAAATGCGGGCCAAGATGTGCACACTGGTATTTCGGTTTTT GGGGCCGCGGGCGGCGACGGGGCCCGTGCGTCCCAGCGCACATGTT CGGCGAGGCGGGGCCTGCGAGCGCGGCCACCGAGAATCGGACGGGG GTAGTCTCAAGCTGGCCGGCCTGCTCTGGTGCCTGGCCTCGCGCCG CCGTGTATCGCCCCGCCCTGGGCGGCAAGGCTGGCCCGGTCGGCAC CAGTTGCGTGAGCGGAAAGATGGCCGCTTCCCGGCCCTGCTGCAGG GAGCTCAAAATGGAGGACGCGGCGCTCGGGAGAGCGGGCGGGTGAG TCACCCACACAAAGGAAAAGGGCCTTTCCGTCCTCAGCCGTCGCTT CATGTGACTCCACGGAGTACCGGGCGCCGTCCAGGCACCTCGATTA GTTCTCGAGCTTTTGGAGTACGTCGTCTTTAGGTTGGGGGGAGGGG TTTTATGCGATGGAGTTTCCCCACACTGAGTGGGTGGAGACTGAAG TTAGGCCAGCTTGGCACTTGATGTAATTCTCCTTGGAATTTGCCCT TTTTGAGTTTGGATCTTGGTTCATTCTCAAGCCTCAGACAGTGGTT CAAAGTTTTTTTCTTCCATTTCAGGTGTCGTGATGCGGCCGCCACC ATGGCCCTGCCCGTGACCGCCCTGCTGCTGCCCCTGGCCCTGCTGC TGCACGCCGCCCGGCCCCAGGTGCAGCTGGTGGAGAGCGGCGGCGG CCTGGTGCAGCCCGGCGGCAGCCTGCGGCTGAGCTGCGTGGCCAGC GGCTTCACCTTCAGCAGCAACGCCATGAGCTGGGTGCGGCAGGCCC CCGGCAAGGGCCTGGAGTGGGTGAGCGCCATCAGCGGCAGCGGCGA CTACACCCACTACAGCGACAGCGTGAAGGGCCGGTTCACCATCAGC CGGGACAACAGCAAGAACACCCTGTACCTGCAGATGAACAGCCTGC GGGCCGAGGACACCGCCGTGTACTACTGCGCCAAGGAGGTGCCCGG CGGCCCCCTGGTGGACTTCGACAGCCGGGGCCAGGGCACCCTGGTG ACCGTGAGCAGCGGCGGCGGCGGCAGCCAGGTGCAGCTGGTGGAGA GCGGCGGCGGCCTGGTGCAGCCCGGCGGCAGCCTGCGGCTGAGCTGCGTGGCCAGCGGCTTCACCTTCAGCAGCAACGCCATGAGCTGGGTGSEQ Construct Name SequenceID NO.CGGCAGGCCCCCGGCAAGGGCCTGGAGTGGGTGAGCGCCATCAGCG GCAGCGGCGACTACACCCACTACAGCGACAGCGTGAAGGGCCGGTT CACCATCAGCCGGGACAACAGCAAGAACACCCTGTACCTGCAGATG AACAGCCTGCGGGCCGAGGACACCGCCGTGTACTACTGCGCCAAGG AGGTGCCCGGCGGCCCCCTGGTGGACTTCGACAGCCGGGGCCAGGG CACCCTGGTGACCGTGAGCAGCACCACCACCCCCGCCCCCCGGCCC CCCACCCCCGCCCCCACCATCGCCAGCCAGCCCCTGAGCCTGCGGC CCGAGGCCTGCCGGCCCGCCGCCGGCGGCGCCGTGCACACCCGGGG CCTGGACTTCGCCTGCGACATCTACATCTGGGCCCCCCTGGCCGGC ACCTGCGGCGTGCTGCTGCTGAGCCTGGTGATCACCCTGTACTGCA AGCGGGGCCGGAAGAAGCTGCTGTACATCTTCAAGCAGCCCTTCAT GCGGCCCGTGCAGACCACCCAGGAGGAGGACGGCTGCAGCTGCCGG TTCCCCGAGGAGGAGGAGGGCGGCTGCGAGCTGCGGGTGAAGTTCA GCCGGAGCGCCGACGCCCCCGCCTACCAGCAGGGCCAGAACCAGCT GTACAACGAGCTGAACCTGGGCCGGCGGGAGGAGTACGACGTGCTG GACAAGCGGCGGGGCCGGGACCCCGAGATGGGCGGCAAGCCCCGGC GGAAGAACCCCCAGGAGGGCCTGTACAACGAGCTGCAGAAGGACAA GATGGCCGAGGCCTACAGCGAGATCGGCATGAAGGGCGAGCGGCGG CGGGGCAAGGGCCACGACGGCCTGTACCAGGGCCTGAGCACCGCCA CCAAGGACACCTACGACGCCCTGCACATGCAGGCCCTGCCCCCCCG GTAATGACCTCGACTGTGCCTTCTAGTTGCCAGCCATCTGTTGTTT GCCCCTCCCCCGTGCCTTCCTTGACCCTGGAAGGTGCCACTCCCAC TGTCCTTTCCTAATAAAATGAGGAAATTGCATCGCATTGTCTGAGT AGGTGTCATTCTATTCTGGGGGGTGGGGTGGGGCAGGACAGCAAGG GGGAGGATTGGGAAGACAATAGCAGGCATGCTGGGGATGCGGTGGG CTCTATGGCTTCTGAGGCGGAAAGAACCAGCTGGGGCTCTAGGGGG TATCCCCACTAGT108 5' AAV2-5ITR TTGGCCACTCCCTCTCTGCGCGCTCGCTCGCTCACTGAGGCCGGGC GACCAAAGGTCGCCCGACGCCCGGGCTTTGCCCGGGCGGCCTCAGT GAGCGAGCGAGCGCGCAGAGAGGGAGTGGCCAACTCCATCACTAGG GGTTCCT109 3' AAV2-5ITR AGGAACCCCTAGTGATGGAGTTGGCCACTCCCTCTCTGCGCGCTCG CTCGCTCACTGAGGCCGCCCGGGCAAAGCCCGGGCGTCGGGCGACC TTTGGTCGCCCGGCCTCAGTGAGCGAGCGAGCGCGCAGAGAGGGAG TGGCCAA110 EFla GGCTCCGGTGCCCGTCAGTGGGCAGAGCGCACATCGCCCACAGTCC CCGAGAAGTTGGGGGGAGGGGTCGGCAATTGAACCGGTGCCTAGAG AAGGTGGCGCGGGGTAAACTGGGAAAGTGATGTCGTGTACTGGCTC CGCCTTTTTCCCGAGGGTGGGGGAGAACCGTATATAAGTGCAGTAG TCGCCGTGAACGTTCTTTTTCGCAACGGGTTTGCCGCCAGAACACA GGTAAGTGCCGTGTGTGGTTCCCGCGGGCCTGGCCTCTTTACGGGT TATGGCCCTTGCGTGCCTTGAATTACTTCCACGCCCCTGGCTGCAG TACGTGATTCTTGATCCCGAGCTTCGGGTTGGAAGTGGGTGGGAGA GTTCGAGGCCTTGCGCTTAAGGAGCCCCTTCGCCTCGTGCTTGAGT TGAGGCCTGGCTTGGGCGCTGGGGCCGCCGCGTGCGAATCTGGTGG CACCTTCGCGCCTGTCTCGCTGCTTTCGATAAGTCTCTAGCCATTT AAAATTTTTGATGACCTGCTGCGACGCTTTTTTTCTGGCAAGATAG TCTTGTAAATGCGGGCCAAGATGTGCACACTGGTATTTCGGTTTTT GGGGCCGCGGGCGGCGACGGGGCCCGTGCGTCCCAGCGCACATGTT CGGCGAGGCGGGGCCTGCGAGCGCGGCCACCGAGAATCGGACGGGG GTAGTCTCAAGCTGGCCGGCCTGCTCTGGTGCCTGGCCTCGCGCCGCCGTGTATCGCCCCGCCCTGGGCGGCAAGGCTGGCCCGGTCGGCACSEQ Construct Name SequenceID NO.CAGTTGCGTGAGCGGAAAGATGGCCGCTTCCCGGCCCTGCTGCAGG GAGCTCAAAATGGAGGACGCGGCGCTCGGGAGAGCGGGCGGGTGAG TCACCCACACAAAGGAAAAGGGCCTTTCCGTCCTCAGCCGTCGCTT CATGTGACTCCACGGAGTACCGGGCGCCGTCCAGGCACCTCGATTA GTTCTCGAGCTTTTGGAGTACGTCGTCTTTAGGTTGGGGGGAGGGG TTTTATGCGATGGAGTTTCCCCACACTGAGTGGGTGGAGACTGAAG TTAGGCCAGCTTGGCACTTGATGTAATTCTCCTTGGAATTTGCCCT TTTTGAGTTTGGATCTTGGTTCATTCTCAAGCCTCAGACAGTGGTT CAAAGTTTTTTTCTTCCATTTCAGGTGTCGTGA200 VHH1 QVKLEESGGGLVQAGRSLRLSCAASEHTFSFR1 aa ofBenchmark 1A,Benchmark 1B201 VHH1 SHVMGCDR1 aa ofBenchmark 1A,Benchmark 1B202 VHH1 WFRQAPGKERESVAFR2 aa ofBenchmark 1A,Benchmark 1B203 VHH1 VIGWRDISTSYADSVKGCDR2 aa ofBenchmark 1A,Benchmark 1B204 VHH1 RFTISRDNAKKTLYLQMNSLKPEDTAVYYCAFR3 aa ofBenchmark 1A,Benchmark 1B205 VHH1 ARRIDAADFDSCDR3 aa ofBenchmark 1A,Benchmark 1B206 VHH1 WGQGTQVTVSSFR4 aa ofBenchmark 1A,Benchmark 1B207 VHH2 FR1 aa of EVQLVESGGGLVQAGGSLRLSCAASGRBenchmark 1A,Benchmark 1B208 VHH2CDR1 aa of TFTMGBenchmark 1A,Benchmark 1B209 VHH2 WFRQAPGKEREFVAFR2 aa ofBenchmark 1A,Benchmark 1B210 VHH2 AISLSPTLAYYAESVKGCDR2 aa ofBenchmark 1A,Benchmark 1BSEQ Construct Name SequenceID NO.211 VHH2 RFTISRDNAKNTVVLQMNSLKPEDTALYYCA FR3 aa ofBenchmark 1A,Benchmark 1B212 VHH2 ADRKSVMSIRPDYCDR3 aa ofBenchmark 1A,Benchmark 1B213 VHH2 WGQGTQVTVSSFR4 aa ofBenchmark 1A,Benchmark 1B214 VL FR1 aa of DIVLTQSPPSLAMSLGKRATISC Benchmark 2A,Benchmark 2B215 VL CDR1 aa of RASESVTILGSHLIHBenchmark 2A,Benchmark 2B216 VL FR2 aa of WYQQKPGQPPTLLIQBenchmark 2A,Benchmark 2B217 VL CDR2 aa of LASNVQTBenchmark 2A,Benchmark 2B218 VL FR3 aa of GVPARFSGSGSRTDFTLTIDPVEEDDVAVYYC Benchmark 2A,Benchmark 2B219 VL CDR3 aa of LQSRTIPRTBenchmark 2A,Benchmark 2B220 VL FR4 aa of FGGGTKLEIKBenchmark 2A,Benchmark 2B221 Linker aa of GSTSGSGKPGSGEGSTKGBenchmark 2A,Benchmark 2B222 VH FR1 aa of QIQLVQSGPELKKPGETVKISCKASGYTFT Benchmark 2A,Benchmark 2B223 VH CDR1 aa of DY SINBenchmark 2A,Benchmark 2B224 VH FR2 aa of WVKRAPGKGLKWMGBenchmark 2A,Benchmark 2B225 VH CDR2 aa of WINTETREPAYAYDFRGBenchmark 2A,Benchmark 2B226 VH FR3 aa of RFAFSLETSASTAYLQINNLKYEDTATYFCAL Benchmark2A, Benchmark2BSEQ Construct Name SequenceID NO.227 VH CDR3 aa of DYSYAMDYBenchmark 2A,Benchmark 2B228 VH FR4 aa of WGQGTSVTVSSBenchmark 2A,Benchmark 2B229 CD8a Hinge aa AAATTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFA of Benchmark CD2A, Benchmark2B230 Construct 1 ATGGCCCTGCCCGTGACCGCCCTGCTGCTGCCCCTGGCCCTGCTGC CAR Full DNA TGCACGCCGCCCGGCCCCAGGTGCAGCTGGTGGAGAGCGGCGGCGG CCTGGTGCAGCCCGGCGGCAGCCTGCGGCTGAGCTGCGTGGCCAGC GGCTTCACCTTCAGCAGCAACGCCATGAGCTGGGTGCGGCAGGCCC CCGGCAAGGGCCTGGAGTGGGTGAGCGCCATCAGCGGCAGCGGCGA CTACACCCACTACAGCGACAGCGTGAAGGGCCGGTTCACCATCAGC CGGGACAACAGCAAGAACACCCTGTACCTGCAGATGAACAGCCTGC GGGCCGAGGACACCGCCGTGTACTACTGCGCCAAGGAGGTGCCCGG CGGCCCCCTGGTGGACTTCGACAGCCGGGGCCAGGGCACCCTGGTG ACCGTGAGCAGCACCACCACCCCCGCCCCCCGGCCCCCCACCCCCG CCCCCACCATCGCCAGCCAGCCCCTGAGCCTGCGGCCCGAGGCCTG CCGGCCCGCCGCCGGCGGCGCCGTGCACACCCGGGGCCTGGACTTC GCCTGCGACATCTACATCTGGGCCCCCCTGGCCGGCACCTGCGGCG TGCTGCTGCTGAGCCTGGTGATCACCCTGTACTGCAAGCGGGGCCG GAAGAAGCTGCTGTACATCTTCAAGCAGCCCTTCATGCGGCCCGTG CAGACCACCCAGGAGGAGGACGGCTGCAGCTGCCGGTTCCCCGAGG AGGAGGAGGGCGGCTGCGAGCTGCGGGTGAAGTTCAGCCGGAGCGC CGACGCCCCCGCCTACCAGCAGGGCCAGAACCAGCTGTACAACGAG CTGAACCTGGGCCGGCGGGAGGAGTACGACGTGCTGGACAAGCGGC GGGGCCGGGACCCCGAGATGGGCGGCAAGCCCCGGCGGAAGAACCC CCAGGAGGGCCTGTACAACGAGCTGCAGAAGGACAAGATGGCCGAG GCCTACAGCGAGATCGGCATGAAGGGCGAGCGGCGGCGGGGCAAGG GCCACGACGGCCTGTACCAGGGCCTGAGCACCGCCACCAAGGACAC CTACGACGCCCTGCACATGCAGGCCCTGCCCCCCCGGTAATGA231 Construct 1 MALPVTALLLPLALLLHAARPQVQLVESGGGLVQPGGSLRLSCVAS CAR full AA GFTFSSNAMSWVRQAPGKGLEWVSAISGSGDYTHYSDSVKGRFTIS RDNSKNTLYLQMNSLRAEDTAVYYCAKEVPGGPLVDFDSRGQGTLV TVSSTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDF ACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPFMRPV QTTQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYQQGQNQLYNE LNLGRREEYDVLDKRRGRDPEMGGKPRRKNPQEGLYNELQKDKMAE AYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR232 Construct 3 ATGGCCCTGCCCGTGACCGCCCTGCTGCTGCCCCTGGCCCTGCTGC CAR full DNA TGCACGCCGCCCGGCCCCAGGTGCAGCTGGTGGAGAGCGGCGGCGG CCTGGTGCAGCCCGGCGGCAGCCTGCGGCTGAGCTGCGTGGCCAGC GGCTTCACCTTCAGCAGCAACGCCATGAGCTGGGTGCGGCAGGCCC CCGGCAAGGGCCTGGAGTGGGTGAGCGCCATCAGCGGCAGCGGCGACTACACCCACTACAGCGACAGCGTGAAGGGCCGGTTCACCATCAGCSEQ Construct Name SequenceID NO.CGGGACAACAGCAAGAACACCCTGTACCTGCAGATGAACAGCCTGC GGGCCGAGGACACCGCCGTGTACTACTGCGCCAAGGAGGTGCCCGG CGGCCCCCTGGTGGACTTCGACAGCCGGGGCCAGGGCACCCTGGTG ACCGTGAGCAGCGGCGGCGGCGGCAGCGGCGGCGGCGGCAGCCAGG TGCAGCTGGTGGAGAGCGGCGGCGGCCTGGTGCAGCCCGGCGGCAG CCTGCGGCTGAGCTGCGTGGCCAGCGGCTTCACCTTCAGCAGCAAC GCCATGAGCTGGGTGCGGCAGGCCCCCGGCAAGGGCCTGGAGTGGG TGAGCGCCATCAGCGGCAGCGGCGACTACACCCACTACAGCGACAG CGTGAAGGGCCGGTTCACCATCAGCCGGGACAACAGCAAGAACACC CTGTACCTGCAGATGAACAGCCTGCGGGCCGAGGACACCGCCGTGT ACTACTGCGCCAAGGAGGTGCCCGGCGGCCCCCTGGTGGACTTCGA CAGCCGGGGCCAGGGCACCCTGGTGACCGTGAGCAGCACCACCACC CCCGCCCCCCGGCCCCCCACCCCCGCCCCCACCATCGCCAGCCAGC CCCTGAGCCTGCGGCCCGAGGCCTGCCGGCCCGCCGCCGGCGGCGC CGTGCACACCCGGGGCCTGGACTTCGCCTGCGACATCTACATCTGG GCCCCCCTGGCCGGCACCTGCGGCGTGCTGCTGCTGAGCCTGGTGA TCACCCTGTACTGCAAGCGGGGCCGGAAGAAGCTGCTGTACATCTT CAAGCAGCCCTTCATGCGGCCCGTGCAGACCACCCAGGAGGAGGAC GGCTGCAGCTGCCGGTTCCCCGAGGAGGAGGAGGGCGGCTGCGAGC TGCGGGTGAAGTTCAGCCGGAGCGCCGACGCCCCCGCCTACCAGCA GGGCCAGAACCAGCTGTACAACGAGCTGAACCTGGGCCGGCGGGAG GAGTACGACGTGCTGGACAAGCGGCGGGGCCGGGACCCCGAGATGG GCGGCAAGCCCCGGCGGAAGAACCCCCAGGAGGGCCTGTACAACGA GCTGCAGAAGGACAAGATGGCCGAGGCCTACAGCGAGATCGGCATG AAGGGCGAGCGGCGGCGGGGCAAGGGCCACGACGGCCTGTACCAGG GCCTGAGCACCGCCACCAAGGACACCTACGACGCCCTGCACATGCA GGCCCTGCCCCCCCGGTAATGA233 Construct 3 MALPVTALLLPLALLLHAARPQVQLVESGGGLVQPGGSLRLSCVAS CAR full AA GFTFSSNAMSWVRQAPGKGLEWVSAISGSGDYTHYSDSVKGRFTIS RDNSKNTLYLQMNSLRAEDTAVYYCAKEVPGGPLVDFDSRGQGTLV TVSSGGGGSGGGGSQVQLVESGGGLVQPGGSLRLSCVASGFTFSSN AMSWVRQAPGKGLEWVSAISGSGDYTHYSDSVKGRFTISRDNSKNT LYLQMNSLRAEDTAVYYCAKEVPGGPLVDFDSRGQGTLVTVSSTTT PAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIW APLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPFMRPVQTTQEED GCSCRFPEEEEGGCELRVKFSRSADAPAYQQGQNQLYNELNLGRRE EYDVLDKRRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGM KGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR234 Construct 4 ATGGCCCTGCCCGTGACCGCCCTGCTGCTGCCCCTGGCCCTGCTGC CAR full DNA TGCACGCCGCCCGGCCCCAGGTGCAGCTGGTGGAGAGCGGCGGCGG CCTGGTGCAGCCCGGCGGCAGCCTGCGGCTGAGCTGCGTGGCCAGC GGCTTCACCTTCAGCAGCAACGCCATGAGCTGGGTGCGGCAGGCCC CCGGCAAGGGCCTGGAGTGGGTGAGCGCCATCAGCGGCAGCGGCGA CTACACCCACTACAGCGACAGCGTGAAGGGCCGGTTCACCATCAGC CGGGACAACAGCAAGAACACCCTGTACCTGCAGATGAACAGCCTGC GGGCCGAGGACACCGCCGTGTACTACTGCGCCAAGGAGGTGCCCGG CGGCCCCCTGGTGGACTTCGACAGCCGGGGCCAGGGCACCCTGGTG ACCGTGAGCAGCGGCGGCGGCGGCAGCGGCGGCGGCGGCAGCGGCG GCGGCGGCAGCCAGGTGCAGCTGGTGGAGAGCGGCGGCGGCCTGGT GCAGCCCGGCGGCAGCCTGCGGCTGAGCTGCGTGGCCAGCGGCTTC ACCTTCAGCAGCAACGCCATGAGCTGGGTGCGGCAGGCCCCCGGCAAGGGCCTGGAGTGGGTGAGCGCCATCAGCGGCAGCGGCGACTACACSEQ Construct Name SequenceID NO.CCACTACAGCGACAGCGTGAAGGGCCGGTTCACCATCAGCCGGGAC AACAGCAAGAACACCCTGTACCTGCAGATGAACAGCCTGCGGGCCG AGGACACCGCCGTGTACTACTGCGCCAAGGAGGTGCCCGGCGGCCC CCTGGTGGACTTCGACAGCCGGGGCCAGGGCACCCTGGTGACCGTG AGCAGCACCACCACCCCCGCCCCCCGGCCCCCCACCCCCGCCCCCA CCATCGCCAGCCAGCCCCTGAGCCTGCGGCCCGAGGCCTGCCGGCC CGCCGCCGGCGGCGCCGTGCACACCCGGGGCCTGGACTTCGCCTGC GACATCTACATCTGGGCCCCCCTGGCCGGCACCTGCGGCGTGCTGC TGCTGAGCCTGGTGATCACCCTGTACTGCAAGCGGGGCCGGAAGAA GCTGCTGTACATCTTCAAGCAGCCCTTCATGCGGCCCGTGCAGACC ACCCAGGAGGAGGACGGCTGCAGCTGCCGGTTCCCCGAGGAGGAGG AGGGCGGCTGCGAGCTGCGGGTGAAGTTCAGCCGGAGCGCCGACGC CCCCGCCTACCAGCAGGGCCAGAACCAGCTGTACAACGAGCTGAAC CTGGGCCGGCGGGAGGAGTACGACGTGCTGGACAAGCGGCGGGGCC GGGACCCCGAGATGGGCGGCAAGCCCCGGCGGAAGAACCCCCAGGA GGGCCTGTACAACGAGCTGCAGAAGGACAAGATGGCCGAGGCCTAC AGCGAGATCGGCATGAAGGGCGAGCGGCGGCGGGGCAAGGGCCACG ACGGCCTGTACCAGGGCCTGAGCACCGCCACCAAGGACACCTACGA CGCCCTGCACATGCAGGCCCTGCCCCCCCGGTAATGA235 Construct 4 MALPVTALLLPLALLLHAARPQVQLVESGGGLVQPGGSLRLSCVAS CAR full AA GFTFSSNAMSWVRQAPGKGLEWVSAISGSGDYTHYSDSVKGRFTIS RDNSKNTLYLQMNSLRAEDTAVYYCAKEVPGGPLVDFDSRGQGTLV TVSSGGGGSGGGGSGGGGSQVQLVESGGGLVQPGGSLRLSCVASGF TFSSNAMSWVRQAPGKGLEWVSAISGSGDYTHYSDSVKGRFTISRD NSKNTLYLQMNSLRAEDTAVYYCAKEVPGGPLVDFDSRGQGTLVTV SSTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFAC DIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPFMRPVQT TQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYQQGQNQLYNELN LGRREEYDVLDKRRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAY SEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR236 Construct 5 ATGGCCCTGCCCGTGACCGCCCTGCTGCTGCCCCTGGCCCTGCTGC CAR full DNA TGCACGCCGCCCGGCCCCAGGTGCAGCTGGTGGAGAGCGGCGGCGG CCTGGTGCAGCCCGGCGGCAGCCTGCGGCTGAGCTGCGTGGCCAGC GGCTTCACCTTCAGCAGCAACGCCATGAGCTGGGTGCGGCAGGCCC CCGGCAAGGGCCTGGAGTGGGTGAGCGCCATCAGCGGCAGCGGCGA CTACACCCACTACAGCGACAGCGTGAAGGGCCGGTTCACCATCAGC CGGGACAACAGCAAGAACACCCTGTACCTGCAGATGAACAGCCTGC GGGCCGAGGACACCGCCGTGTACTACTGCGCCAAGGAGGTGCCCGG CGGCCCCCTGGTGGACTTCGACAGCCGGGGCCAGGGCACCCTGGTG ACCGTGAGCAGCGGCGGCGGCGGCAGCGGCGGCGGCGGCAGCGGCG GCGGCGGCAGCGGCGGCGGCGGCAGCCAGGTGCAGCTGGTGGAGAG CGGCGGCGGCCTGGTGCAGCCCGGCGGCAGCCTGCGGCTGAGCTGC GTGGCCAGCGGCTTCACCTTCAGCAGCAACGCCATGAGCTGGGTGC GGCAGGCCCCCGGCAAGGGCCTGGAGTGGGTGAGCGCCATCAGCGG CAGCGGCGACTACACCCACTACAGCGACAGCGTGAAGGGCCGGTTC ACCATCAGCCGGGACAACAGCAAGAACACCCTGTACCTGCAGATGA ACAGCCTGCGGGCCGAGGACACCGCCGTGTACTACTGCGCCAAGGA GGTGCCCGGCGGCCCCCTGGTGGACTTCGACAGCCGGGGCCAGGGC ACCCTGGTGACCGTGAGCAGCACCACCACCCCCGCCCCCCGGCCCC CCACCCCCGCCCCCACCATCGCCAGCCAGCCCCTGAGCCTGCGGCC CGAGGCCTGCCGGCCCGCCGCCGGCGGCGCCGTGCACACCCGGGGCCTGGACTTCGCCTGCGACATCTACATCTGGGCCCCCCTGGCCGGCASEQ Construct Name SequenceID NO.CCTGCGGCGTGCTGCTGCTGAGCCTGGTGATCACCCTGTACTGCAA GCGGGGCCGGAAGAAGCTGCTGTACATCTTCAAGCAGCCCTTCATG CGGCCCGTGCAGACCACCCAGGAGGAGGACGGCTGCAGCTGCCGGT TCCCCGAGGAGGAGGAGGGCGGCTGCGAGCTGCGGGTGAAGTTCAG CCGGAGCGCCGACGCCCCCGCCTACCAGCAGGGCCAGAACCAGCTG TACAACGAGCTGAACCTGGGCCGGCGGGAGGAGTACGACGTGCTGG ACAAGCGGCGGGGCCGGGACCCCGAGATGGGCGGCAAGCCCCGGCG GAAGAACCCCCAGGAGGGCCTGTACAACGAGCTGCAGAAGGACAAG ATGGCCGAGGCCTACAGCGAGATCGGCATGAAGGGCGAGCGGCGGC GGGGCAAGGGCCACGACGGCCTGTACCAGGGCCTGAGCACCGCCAC CAAGGACACCTACGACGCCCTGCACATGCAGGCCCTGCCCCCCCGG TAATGA237 Construct 5 MALPVTALLLPLALLLHAARPQVQLVESGGGLVQPGGSLRLSCVAS CAR full AA GFTFSSNAMSWVRQAPGKGLEWVSAISGSGDYTHYSDSVKGRFTIS RDNSKNTLYLQMNSLRAEDTAVYYCAKEVPGGPLVDFDSRGQGTLV TVSSGGGGSGGGGSGGGGSGGGGSQVQLVESGGGLVQPGGSLRLSC VASGFTFSSNAMSWVRQAPGKGLEWVSAISGSGDYTHYSDSVKGRF TISRDNSKNTLYLQMNSLRAEDTAVYYCAKEVPGGPLVDFDSRGQG TLVTVSSTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRG LDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPFM RPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYQQGQNQL YNELNLGRREEYDVLDKRRGRDPEMGGKPRRKNPQEGLYNELQKDK MAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR238 Construct 6 ATGGCCCTGCCCGTGACCGCCCTGCTGCTGCCCCTGGCCCTGCTGC CAR full DNA TGCACGCCGCCCGGCCCCAGGTGCAGCTGGTGGAGAGCGGCGGCGG CCTGGTGCAGCCCGGCGGCAGCCTGCGGCTGAGCTGCGTGGCCAGC GGCTTCACCTTCAGCAGCAACGCCATGAGCTGGGTGCGGCAGGCCC CCGGCAAGGGCCTGGAGTGGGTGAGCGCCATCAGCGGCAGCGGCGA CTACACCCACTACAGCGACAGCGTGAAGGGCCGGTTCACCATCAGC CGGGACAACAGCAAGAACACCCTGTACCTGCAGATGAACAGCCTGC GGGCCGAGGACACCGCCGTGTACTACTGCGCCAAGGAGGTGCCCGG CGGCCCCCTGGTGGACTTCGACAGCCGGGGCCAGGGCACCCTGGTG ACCGTGAGCAGCGGCGGCGGCGGCAGCGGCGGCGGCGGCAGCGGCG GCGGCGGCAGCGGCGGCGGCGGCAGCGGCGGCGGCGGCAGCCAGGT GCAGCTGGTGGAGAGCGGCGGCGGCCTGGTGCAGCCCGGCGGCAGC CTGCGGCTGAGCTGCGTGGCCAGCGGCTTCACCTTCAGCAGCAACG CCATGAGCTGGGTGCGGCAGGCCCCCGGCAAGGGCCTGGAGTGGGT GAGCGCCATCAGCGGCAGCGGCGACTACACCCACTACAGCGACAGC GTGAAGGGCCGGTTCACCATCAGCCGGGACAACAGCAAGAACACCC TGTACCTGCAGATGAACAGCCTGCGGGCCGAGGACACCGCCGTGTA CTACTGCGCCAAGGAGGTGCCCGGCGGCCCCCTGGTGGACTTCGAC AGCCGGGGCCAGGGCACCCTGGTGACCGTGAGCAGCACCACCACCC CCGCCCCCCGGCCCCCCACCCCCGCCCCCACCATCGCCAGCCAGCC CCTGAGCCTGCGGCCCGAGGCCTGCCGGCCCGCCGCCGGCGGCGCC GTGCACACCCGGGGCCTGGACTTCGCCTGCGACATCTACATCTGGG CCCCCCTGGCCGGCACCTGCGGCGTGCTGCTGCTGAGCCTGGTGAT CACCCTGTACTGCAAGCGGGGCCGGAAGAAGCTGCTGTACATCTTC AAGCAGCCCTTCATGCGGCCCGTGCAGACCACCCAGGAGGAGGACG GCTGCAGCTGCCGGTTCCCCGAGGAGGAGGAGGGCGGCTGCGAGCT GCGGGTGAAGTTCAGCCGGAGCGCCGACGCCCCCGCCTACCAGCAG GGCCAGAACCAGCTGTACAACGAGCTGAACCTGGGCCGGCGGGAGGAGTACGACGTGCTGGACAAGCGGCGGGGCCGGGACCCCGAGATGGGSEQ Construct Name SequenceID NO.CGGCAAGCCCCGGCGGAAGAACCCCCAGGAGGGCCTGTACAACGAG CTGCAGAAGGACAAGATGGCCGAGGCCTACAGCGAGATCGGCATGA AGGGCGAGCGGCGGCGGGGCAAGGGCCACGACGGCCTGTACCAGGG CCTGAGCACCGCCACCAAGGACACCTACGACGCCCTGCACATGCAG GCCCTGCCCCCCCGGTAATGA239 Construct 6 MALPVTALLLPLALLLHAARPQVQLVESGGGLVQPGGSLRLSCVAS CAR full AA GFTFSSNAMSWVRQAPGKGLEWVSAISGSGDYTHYSDSVKGRFTIS RDNSKNTLYLQMNSLRAEDTAVYYCAKEVPGGPLVDFDSRGQGTLV TVSSGGGGSGGGGSGGGGSGGGGSGGGGSQVQLVESGGGLVQPGGS LRLSCVASGFTFSSNAMSWVRQAPGKGLEWVSAISGSGDYTHYSDS VKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKEVPGGPLVDFD SRGQGTLVTVSSTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGA VHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIF KQPFMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYQQ GQNQLYNELNLGRREEYDVLDKRRGRDPEMGGKPRRKNPQEGLYNE LQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQ ALPPR240 Construct 7 ATGGCCCTGCCCGTGACCGCCCTGCTGCTGCCCCTGGCCCTGCTGC CAR full DNA TGCACGCCGCCCGGCCCCAGGTGCAGCTGGTGGAGAGCGGCGGCGG CCTGGTGCAGCCCGGCGGCAGCCTGCGGCTGAGCTGCGTGGCCAGC GGCTTCACCTTCAGCAGCAACGCCATGAGCTGGGTGCGGCAGGCCC CCGGCAAGGGCCTGGAGTGGGTGAGCGCCATCAGCGGCAGCGGCGA CTACACCCACTACAGCGACAGCGTGAAGGGCCGGTTCACCATCAGC CGGGACAACAGCAAGAACACCCTGTACCTGCAGATGAACAGCCTGC GGGCCGAGGACACCGCCGTGTACTACTGCGCCAAGGAGGTGCCCGG CGGCCCCCTGGTGGACTTCGACAGCCGGGGCCAGGGCACCCTGGTG ACCGTGAGCAGCGGCGGCGGCGGCAGCCAGGTGCAGCTGGTGGAGA GCGGCGGCGGCCTGGTGCAGCCCGGCGGCAGCCTGCGGCTGAGCTG CGTGGCCAGCGGCTTCACCTTCAGCAGCAACGCCATGAGCTGGGTG CGGCAGGCCCCCGGCAAGGGCCTGGAGTGGGTGAGCGCCATCAGCG GCAGCGGCGACTACACCCACTACAGCGACAGCGTGAAGGGCCGGTT CACCATCAGCCGGGACAACAGCAAGAACACCCTGTACCTGCAGATG AACAGCCTGCGGGCCGAGGACACCGCCGTGTACTACTGCGCCAAGG AGGTGCCCGGCGGCCCCCTGGTGGACTTCGACAGCCGGGGCCAGGG CACCCTGGTGACCGTGAGCAGCACCACCACCCCCGCCCCCCGGCCC CCCACCCCCGCCCCCACCATCGCCAGCCAGCCCCTGAGCCTGCGGC CCGAGGCCTGCCGGCCCGCCGCCGGCGGCGCCGTGCACACCCGGGG CCTGGACTTCGCCTGCGACTTCTGGGTGCTGGTGGTGGTGGGCGGC GTGCTGGCCTGCTACAGCCTGCTGGTGACCGTGGCCTTCATCATCT TCTGGGTGCGGAGCAAGCGGAGCCGGCTGCTGCACAGCGACTACAT GAACATGACCCCCCGGCGGCCCGGCCCCACCCGGAAGCACTACCAG CCCTACGCCCCCCCCCGGGACTTCGCCGCCTACCGGAGCCGGGTGA AGTTCAGCCGGAGCGCCGACGCCCCCGCCTACCAGCAGGGCCAGAA CCAGCTGTACAACGAGCTGAACCTGGGCCGGCGGGAGGAGTACGAC GTGCTGGACAAGCGGCGGGGCCGGGACCCCGAGATGGGCGGCAAGC CCCGGCGGAAGAACCCCCAGGAGGGCCTGTACAACGAGCTGCAGAA GGACAAGATGGCCGAGGCCTACAGCGAGATCGGCATGAAGGGCGAG CGGCGGCGGGGCAAGGGCCACGACGGCCTGTACCAGGGCCTGAGCA CCGCCACCAAGGACACCTACGACGCCCTGCACATGCAGGCCCTGCC CCCCCGGTAATGA241 Construct 7 MALPVTALLLPLALLLHAARPQVQLVESGGGLVQPGGSLRLSCVASCAR full AA GFTFSSNAMSWVRQAPGKGLEWVSAISGSGDYTHYSDSVKGRFTISSEQ Construct Name SequenceID NO.RDNSKNTLYLQMNSLRAEDTAVYYCAKEVPGGPLVDFDSRGQGTLV TVSSGGGGSQVQLVESGGGLVQPGGSLRLSCVASGFTFSSNAMSWV RQAPGKGLEWVSAISGSGDYTHYSDSVKGRFTISRDNSKNTLYLQM NSLRAEDTAVYYCAKEVPGGPLVDFDSRGQGTLVTVSSTTTPAPRP PTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDFWVLVVVGG VLACYSLLVTVAFIIFWVRSKRSRLLHSDYMNMTPRRPGPTRKHYQ PYAPPRDFAAYRSRVKFSRSADAPAYQQGQNQLYNELNLGRREEYD VLDKRRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGE RRRGKGHDGLYQGLSTATKDTYDALHMQALPPR242 Construct 8 ATGGCCCTGCCCGTGACCGCCCTGCTGCTGCCCCTGGCCCTGCTGC CAR full DNA TGCACGCCGCCCGGCCCCAGGTGCAGCTGGTGGAGAGCGGCGGCGG CCTGGTGCAGCCCGGCGGCAGCCTGCGGCTGAGCTGCGTGGCCAGC GGCTTCACCTTCAGCAGCAACGCCATGAGCTGGGTGCGGCAGGCCC CCGGCAAGGGCCTGGAGTGGGTGAGCGCCATCAGCGGCAGCGGCGA CTACACCCACTACAGCGACAGCGTGAAGGGCCGGTTCACCATCAGC CGGGACAACAGCAAGAACACCCTGTACCTGCAGATGAACAGCCTGC GGGCCGAGGACACCGCCGTGTACTACTGCGCCAAGGAGGTGCCCGG CGGCCCCCTGGTGGACTTCGACAGCCGGGGCCAGGGCACCCTGGTG ACCGTGAGCAGCGGCGGCGGCGGCAGCCAGGTGCAGCTGGTGGAGA GCGGCGGCGGCCTGGTGCAGCCCGGCGGCAGCCTGCGGCTGAGCTG CGTGGCCAGCGGCTTCACCTTCAGCAGCAACGCCATGAGCTGGGTG CGGCAGGCCCCCGGCAAGGGCCTGGAGTGGGTGAGCGCCATCAGCG GCAGCGGCGACTACACCCACTACAGCGACAGCGTGAAGGGCCGGTT CACCATCAGCCGGGACAACAGCAAGAACACCCTGTACCTGCAGATG AACAGCCTGCGGGCCGAGGACACCGCCGTGTACTACTGCGCCAAGG AGGTGCCCGGCGGCCCCCTGGTGGACTTCGACAGCCGGGGCCAGGG CACCCTGGTGACCGTGAGCAGCACCACCACCCCCGCCCCCCGGCCC CCCACCCCCGCCCCCACCATCGCCAGCCAGCCCCTGAGCCTGCGGC CCGAGGCCTGCCGGCCCGCCGCCGGCGGCGCCGTGCACACCCGGGG CCTGGACTTCGCCTGCGACTTCTGGGTGCTGGTGGTGGTGGGCGGC GTGCTGGCCTGCTACAGCCTGCTGGTGACCGTGGCCTTCATCATCT TCTGGGTGAAGCGGGGCCGGAAGAAGCTGCTGTACATCTTCAAGCA GCCCTTCATGCGGCCCGTGCAGACCACCCAGGAGGAGGACGGCTGC AGCTGCCGGTTCCCCGAGGAGGAGGAGGGCGGCTGCGAGCTGCGGG TGAAGTTCAGCCGGAGCGCCGACGCCCCCGCCTACCAGCAGGGCCA GAACCAGCTGTACAACGAGCTGAACCTGGGCCGGCGGGAGGAGTAC GACGTGCTGGACAAGCGGCGGGGCCGGGACCCCGAGATGGGCGGCA AGCCCCGGCGGAAGAACCCCCAGGAGGGCCTGTACAACGAGCTGCA GAAGGACAAGATGGCCGAGGCCTACAGCGAGATCGGCATGAAGGGC GAGCGGCGGCGGGGCAAGGGCCACGACGGCCTGTACCAGGGCCTGA GCACCGCCACCAAGGACACCTACGACGCCCTGCACATGCAGGCCCT GCCCCCCCGGTAATGA243 Construct 8 MALPVTALLLPLALLLHAARPQVQLVESGGGLVQPGGSLRLSCVAS CAR full AA GFTFSSNAMSWVRQAPGKGLEWVSAISGSGDYTHYSDSVKGRFTIS RDNSKNTLYLQMNSLRAEDTAVYYCAKEVPGGPLVDFDSRGQGTLV TVSSGGGGSQVQLVESGGGLVQPGGSLRLSCVASGFTFSSNAMSWV RQAPGKGLEWVSAISGSGDYTHYSDSVKGRFTISRDNSKNTLYLQM NSLRAEDTAVYYCAKEVPGGPLVDFDSRGQGTLVTVSSTTTPAPRP PTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDFWVLVVVGG VLACYSLLVTVAFIIFWVKRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYQQGQNQLYNELNLGRREEYSEQ Construct Name SequenceID NO.DVLDKRRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKG ERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR244 Construct 9 ATGGCCCTGCCCGTGACCGCCCTGCTGCTGCCCCTGGCCCTGCTGC CAR full DNA TGCACGCCGCCCGGCCCCAGGTGCAGCTGGTGGAGAGCGGCGGCGG CCTGGTGCAGCCCGGCGGCAGCCTGCGGCTGAGCTGCGTGGCCAGC GGCTTCACCTTCAGCAGCAACGCCATGAGCTGGGTGCGGCAGGCCC CCGGCAAGGGCCTGGAGTGGGTGAGCGCCATCAGCGGCAGCGGCGA CTACACCCACTACAGCGACAGCGTGAAGGGCCGGTTCACCATCAGC CGGGACAACAGCAAGAACACCCTGTACCTGCAGATGAACAGCCTGC GGGCCGAGGACACCGCCGTGTACTACTGCGCCAAGGAGGTGCCCGG CGGCCCCCTGGTGGACTTCGACAGCCGGGGCCAGGGCACCCTGGTG ACCGTGAGCAGCGGCGGCGGCGGCAGCCAGGTGCAGCTGGTGGAGA GCGGCGGCGGCCTGGTGCAGCCCGGCGGCAGCCTGCGGCTGAGCTG CGTGGCCAGCGGCTTCACCTTCAGCAGCAACGCCATGAGCTGGGTG CGGCAGGCCCCCGGCAAGGGCCTGGAGTGGGTGAGCGCCATCAGCG GCAGCGGCGACTACACCCACTACAGCGACAGCGTGAAGGGCCGGTT CACCATCAGCCGGGACAACAGCAAGAACACCCTGTACCTGCAGATG AACAGCCTGCGGGCCGAGGACACCGCCGTGTACTACTGCGCCAAGG AGGTGCCCGGCGGCCCCCTGGTGGACTTCGACAGCCGGGGCCAGGG CACCCTGGTGACCGTGAGCAGCACCACCACCCCCGCCCCCCGGCCC CCCACCCCCGCCCCCACCATCGCCAGCCAGCCCCTGAGCCTGCGGC CCGAGGCCTGCCGGCCCGCCGCCGGCGGCGCCGTGCACACCCGGGG CCTGGACTTCGCCTGCGACATCTACATCTGGGCCCCCCTGGCCGGC ACCTGCGGCGTGCTGCTGCTGAGCCTGGTGATCACCCTGTACTGCC GGAGCAAGCGGAGCCGGCTGCTGCACAGCGACTACATGAACATGAC CCCCCGGCGGCCCGGCCCCACCCGGAAGCACTACCAGCCCTACGCC CCCCCCCGGGACTTCGCCGCCTACCGGAGCCGGGTGAAGTTCAGCC GGAGCGCCGACGCCCCCGCCTACCAGCAGGGCCAGAACCAGCTGTA CAACGAGCTGAACCTGGGCCGGCGGGAGGAGTACGACGTGCTGGAC AAGCGGCGGGGCCGGGACCCCGAGATGGGCGGCAAGCCCCGGCGGA AGAACCCCCAGGAGGGCCTGTACAACGAGCTGCAGAAGGACAAGAT GGCCGAGGCCTACAGCGAGATCGGCATGAAGGGCGAGCGGCGGCGG GGCAAGGGCCACGACGGCCTGTACCAGGGCCTGAGCACCGCCACCA AGGACACCTACGACGCCCTGCACATGCAGGCCCTGCCCCCCCGGTA AT GA245 Construct 9 MALPVTALLLPLALLLHAARPQVQLVESGGGLVQPGGSLRLSCVAS CAR full AA GFTFSSNAMSWVRQAPGKGLEWVSAISGSGDYTHYSDSVKGRFTIS RDNSKNTLYLQMNSLRAEDTAVYYCAKEVPGGPLVDFDSRGQGTLV TVSSGGGGSQVQLVESGGGLVQPGGSLRLSCVASGFTFSSNAMSWV RQAPGKGLEWVSAISGSGDYTHYSDSVKGRFTISRDNSKNTLYLQM NSLRAEDTAVYYCAKEVPGGPLVDFDSRGQGTLVTVSSTTTPAPRP PTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAG TCGVLLLSLVITLYCRSKRSRLLHSDYMNMTPRRPGPTRKHYQPYA PPRDFAAYRSRVKFSRSADAPAYQQGQNQLYNELNLGRREEYDVLD KRRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRR GKGHDGLYQGLSTATKDTYDALHMQALPPR246 Construct 10 ATGGCCCTGCCCGTGACCGCCCTGCTGCTGCCCCTGGCCCT CAR full DNA GCTGCTGCACGCCGCCCGGCCCCAGGTGCAGCTGGTGGAG AGCGGCGGCGGCCTGGTGCAGCCCGGCGGCAGCCTGCGGC TGAGCTGCGTGGCCAGCGGCTTCACCTTCAGCAGCAACGC CATGAGCTGGGTGCGGCAGGCCCCCGGCAAGGGCCTGGAGTGGGTGAGCGCCATCAGCGGCAGCGGCGACTACACCCACTSEQ Construct Name SequenceID NO.ACAGCGACAGCGTGAAGGGCCGGTTCACCATCAGCCGGGA CAACAGCAAGAACACCCTGTACCTGCAGATGAACAGCCTG CGGGCCGAGGACACCGCCGTGTACTACTGCGCCAAGGAGG TGCCCGGCGGCCCCCTGGTGGACTTCGACAGCCGGGGCCA GGGCACCCTGGTGACCGTGAGCAGCACCACCACCCCCGCC CCCCGGCCCCCCACCCCCGCCCCCACCATCGCCAGCCAGC CCCTGAGCCTGCGGCCCGAGGCCTGCCGGCCCGCCGCCGG CGGCGCCGTGCACACCCGGGGCCTGGACTTCGCCTGCGAC ATCTACATCTGGGCCCCCCTGGCCGGCACCTGCGGCGTGCT GCTGCTGAGCCTGGTGATCACCCTGTACTGCCGGAGCAAG CGGAGCCGGCTGCTGCACAGCGACTACATGAACATGACCC CCCGGCGGCCCGGCCCCACCCGGAAGCACTACCAGCCCTA CGCCCCCCCCCGGGACTTCGCCGCCTACCGGAGCCGGGTG AAGTTCAGCCGGAGCGCCGACGCCCCCGCCTACCAGCAGG GCCAGAACCAGCTGTACAACGAGCTGAACCTGGGCCGGCG GGAGGAGTACGACGTGCTGGACAAGCGGCGGGGCCGGGA CCCCGAGATGGGCGGCAAGCCCCGGCGGAAGAACCCCCA GGAGGGCCTGTACAACGAGCTGCAGAAGGACAAGATGGC CGAGGCCTACAGCGAGATCGGCATGAAGGGCGAGCGGCG GCGGGGCAAGGGCCACGACGGCCTGTACCAGGGCCTGAG CACCGCCACCAAGGACACCTACGACGCCCTGCACATGCAG GCCCTGCCCCCCCGGTAA247 Construct 10 MALPVTALLLPLALLLHAARPQVQLVESGGGLVQPGGSLRLS CAR full AA CVASGFTFSSNAMSWVRQAPGKGLEWVSAISGSGDYTHYSD SVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKEVPGG PLVDFDSRGQGTLVTVSSTTTPAPRPPTPAPTIASQPLSLRPEA CRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLY CRSKRSRLLHSDYMNMTPRRPGPTRKHYQPYAPPRDFAAYR SRVKFSRSADAPAYQQGQNQLYNELNLGRREEYDVLDKRRG RDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR[000204] In some embodiments, the present disclosure provides an anti-BCMA chimeric antigen receptor (CAR) comprising: (a) an antigen-binding domain that binds to BCMA, wherein the antigen-binding domain comprises a monospecific, bivalent VHH comprising a first heavy chain variable (VH) region and a second VH region each comprising a complementarity determining region 1 (VH CDR1), a VH CDR2, and VH CDR3 as set forth in the amino acid sequences of SEQ ID NO: 63, SEQ ID NO: 65, and SEQ ID NO: 67, respectively, (b) a transmembrane domain; and (c) an intracellular domain comprising a costimulatory domain comprising an amino acid sequence of SEQ ID NO: 99 or 71 In some embodiments, the present disclosure provides for a nucleic acid encoding the anti-BCMA CAR. In some embodiments, the CAR comprises a monospecific monovalent VHH comprising a complementarity determining region 1 (VH CDR1), a VH CDR2, and VH CDR3 as set forth in the amino acid sequences of SEQ ID NO: 63, SEQ ID NO: 65, and SEQ ID NO: 67,respectively, (b) a transmembrane domain; and (c) an intracellular domain comprising a costimulatory domain comprising an amino acid sequence of SEQ ID NO: 99 or 71.[000205] In some embodiments, the anti-BCMA CAR comprises an antigen-binding region comprising a first and / or a second VH region each comprising an amino acid sequence having at least 90%, 93%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO: 81, or wherein the first and / or the second VH region each comprises the amino acid sequence of SEQ ID NO: 81. In other embodiments, the anti-BCMA CAR comprises an antigen binding protein comprising a first VH region comprising the amino acid sequence of SEQ ID NO: 81, and a second VH region comprising the amino acid sequence of SEQ ID NO: 81.[000206] In some embodiments, the anti-BCMA CAR comprises an amino acid sequence of SEQ ID NO 83. In other embodiments, the anti-BCMA CAR comprises an amino acid sequence of SEQ ID NO: 231, 233, 235, 237, 239, 241, 243, 245, or 247.[000207] In some embodiments, the nucleic acid encoding the anti-BCMA CAR comprises a nucleic acid sequence of any one of SEQ ID NOs:, or a nucleic acid sequence that has at least 90%, 93%, 95%, 96%, 97%, 98%, or 99% identity to any one of SEQ ID NOs: 82, 230, 232, 234, 236, 238, 240, 242, 244, or 246.[000208] In some embodiments, the nucleic acid encoding the anti-BCMA CAR comprises a hinge domain, wherein the hinge domain is encoded by a nucleic acid sequence of any one of SEQ ID NOs: 85-88 or a nucleic acid sequence that has at least 90%, 93%, 95%, 96%, 97%, 98%, or 99% identity to any one of SEQ ID NOs: 85-88.[000209] In some embodiments, the nucleic acid encoding the anti-BCMA CAR comprises a nucleic acid sequence encoding the transmembrane domain comprising a sequence of any one of SEQ ID NOs: 90-92 and 94, or a sequence having at least 90%, 93%, 95%, 96%, 97%, 98%, or 99% identity to any one of SEQ ID NOs: 90-92 and 94.[000210] In some embodiments, the nucleic acid encoding the anti-BCMA CAR comprises an activation domain, wherein the nucleic acid encoding the activation domain comprises a nucleic acid sequence of SEQ ID NO: 102 or 104 or a nucleic acid sequence that has at least 90%, 93%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO: 102 or 104.[000211] In some embodiments, the amino acid sequence of the anti-BCMA CAR is the amino acid sequence of SEQ ID NO: 101. In some embodiments, the amino acid sequence of the anti-BCMA CAR is the amino acid sequence of SEQ ID NO: 231. In some embodiments, the amino acid sequence of the anti-BCMA CAR is the amino acid sequence of SEQ ID NO: 233. In some embodiments, the amino acid sequence of the anti-BCMA CAR is the amino acid sequence of SEQ ID NO: 235. In some embodiments, the amino acid sequence of the anti-BCMA CAR is the amino acid sequence of SEQ ID NO: 237. In some embodiments, the amino acid sequence of the anti-BCMA CAR is the amino acid sequence of SEQ ID NO: 239. In some embodiments, the amino acid sequence of the anti-BCMA CAR is the amino acid sequence of SEQ ID NO: 241. In some embodiments, the amino acid sequence of the anti-BCMA CAR is the amino acid sequence of SEQ ID NO: 243. In some embodiments, the amino acid sequence of the anti-BCMA CAR is the amino acid sequence of SEQ ID NO: 245. In some embodiments, the amino acid sequence of the anti-BCMA CAR is the amino acid sequence of SEQ ID NO: 247.[000212] In some embodiments, the nucleic acid encoding the anti-BCMA CAR comprises a nucleic acid sequence of SEQ ID NO: 82. In some embodiments, the nucleic acid comprises a nucleic acid sequence of SEQ ID NO: 230. In some embodiments, the nucleic acid comprises a nucleic acid sequence of SEQ ID NO: 232. In some embodiments, the nucleic acid comprises a nucleic acid sequence of SEQ ID NO: 234. In some embodiments, the nucleic acid comprises a nucleic acid sequence of SEQ ID NO: 236. In some embodiments, the nucleic acid comprises a nucleic acid sequence of SEQ ID NO: 238. In some embodiments, the nucleic acid comprises a nucleic acid sequence of SEQ ID NO: 240. In some embodiments, the nucleic acid comprises a nucleic acid sequence of SEQ ID NO: 242. In some embodiments, the nucleic acid comprises a nucleic acid sequence of SEQ ID NO: 244. In some embodiments, the nucleic acid comprises a nucleic acid sequence of SEQ ID NO: 246.[000213] In some embodiments, the nucleic acid encodes the amino acid sequence of SEQ ID NO: 101, which describes an anti-BCMA CAR and includes a signal sequence.[000214] In some embodiments, the disclosure provides for an mRNA encoded by the nucleic acid disclosed herein. In some embodiments, the disclosure provides for an expression vector operably linked to or comprising the nucleic acid disclosed herein.[000215] In some aspects, provided herein is a messenger RNA (mRNA) encoding an anti-B cell maturation antigen (BCMA) chimeric antigen receptor (CAR), wherein the anti-BCMA CAR comprises: a) an antigen-binding domain that specifically binds to BCMA, wherein the antigen-binding domain comprises a monospecific, bivalent VHH comprising a first heavy chain variable (VH) region and a second VH region each comprising a complementarity determining region 1 (VH CDR1), a VH CDR2, and VH CDR3 as set forth in the amino acid sequences of SEQ ID NO: 63, SEQ ID NO: 65, and SEQ ID NO: 67, respectively; b) a transmembrane domain; and c) an intracellular domain (ICD) comprising a costimulatory domain comprising an amino acid sequence of SEQ ID NO: 71. In some embodiments, the first and / or the second VH region each comprise an amino acid sequencehaving at least 90%, 93%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO: 81, or the first and / or the second VH region each comprises the amino acid sequence of SEQ ID NO: 81. In some embodiments, the first VH region comprises the amino acid sequence of SEQ ID NO: 81, and the second VH region comprises the amino acid sequence of SEQ ID NO: 81. In some embodiments, the bivalent VHH comprises a linker between the first and second VH regions. In some embodiments, the linker is a glycine-serine linker, e.g., a glycine-serine linker comprising the sequence of SEQ ID NO: 73. In some embodiments, the antigenbinding domain comprises the amino acid sequence of SEQ ID NO: 84. In some embodiments, the transmembrane domain comprises a CD8a transmembrane domain comprising an amino acid sequence of SEQ ID NO: 70. In some embodiments, the anti-BCMA CAR further comprises a hinge domain (e.g., a CD8a hinge domain, or fragment thereof, comprising an amino acid sequence of SEQ ID NO: 69) between the antigen-binding domain and the transmembrane domain. In some embodiments, the intracellular domain further comprises an activation domain, e.g., a CD3z activation domain comprising an amino acid sequence of SEQ ID NO: 72. In some embodiments, the anti-BCMA CAR comprises an amino acid sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 83. In some embodiments, the anti-BCMA CAR comprises the amino acid sequence of SEQ ID NO: 83. In some embodiments, the VH region is encoded by a nucleic acid sequence having at least 90%, 93%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO: 80 and the second VH region is encoded by a nucleic acid sequence having at least 90%, 93%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO: 80. In some embodiments, the anti-BCMA CAR is encoded by a nucleic acid sequence that is at least 95% identical to the nucleic acid sequence of SEQ ID NO: 82.[000216] In some aspects, provided herein is a messenger RNA (mRNA) encoding an anti-BCMA CAR, comprising: a) a first nucleic acid sequence encoding an antigen-binding domain that specifically binds to BCMA, wherein the first nucleic acid sequence comprises the sequence set forth in SEQ ID NO: 3, SEQ ID NO: 5, and SEQ ID NO: 7; b) a second nucleic acid sequence encoding a transmembrane domain; and c) a third nucleic acid sequence encoding a costimulatory domain, wherein the third nucleic acid sequence comprises SEQ ID NO: 11. In some embodiments, the antigen-binding domain comprises a monospecific, bivalent VHH comprising a first heavy chain variable (VH) region and a second VH region each comprising a complementarity determining region 1 (VH CDR1), a VH CDR2, and VH CDR3 as set forth in the amino acid sequences of SEQ ID NO: 63, SEQ ID NO: 65, and SEQ ID NO: 67. In some embodiments, the first and / or thesecond VH region each comprise an amino acid sequence having at least 90%, 93%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO: 81, or wherein the first and / or the second VH region each comprises the amino acid sequence of SEQ ID NO: 81. In some embodiments, the first VH region comprises the amino acid sequence of SEQ ID NO: 81, and the second VH region comprises the amino acid sequence of SEQ ID NO: 81. In some embodiments, the bivalent VHH comprises a linker between the first and second VH regions. In some embodiments, the linker is a glycine-serine linker, e.g., a glycine-serine linker comprising the sequence of SEQ ID NO: 73. In some embodiments, the antigen-binding domain comprises the amino acid sequence of SEQ ID NO: 84. In some embodiments, the transmembrane domain comprises a CD8a transmembrane domain comprising an amino acid sequence of SEQ ID NO: 70. In some embodiments, the anti-BCMA CAR further comprises a hinge domain (e.g., a CD8a hinge domain, or fragment thereof, comprising an amino acid sequence of SEQ ID NO: 69) between the antigen-binding domain and the transmembrane domain. In some embodiments, the anti-BCMA CAR further comprises an activation domain, e.g., a CD3z activation domain comprising an amino acid sequence of SEQ ID NO: 72. In some embodiments, the anti-BCMA CAR comprises an amino acid sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 83. In some embodiments, the anti-BCMA CAR comprises the amino acid sequence of SEQ ID NO: 83. In some embodiments, the VH region is encoded by a nucleic acid sequence having at least 90%, 93%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO: 80 and the second VH region is encoded by a nucleic acid sequence having at least 90%, 93%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO: 80. In some embodiments, the anti-BCMA CAR is encoded by a nucleic acid sequence that is at least 95% identical to the nucleic acid sequence of SEQ ID NO: 82. The embodiments described herein provide exemplary nucleic acid sequences (e.g., SEQ ID Nos: 3, 5, and 7). It is understood that if a DNA sequence (comprising Ts) is referenced with respect to an RNA, then Ts should be replaced with Us (which may be modified or unmodified depending on the context), and vice versa. Examples of modified U include, e.g., Nl-methyl-pseudouridine, pseudouridine, 5-methoxy uridine, and 5-iodouridine.[000217] In some aspects, provided herein is a messenger RNA (mRNA) encoding an anti-BCMA CAR, comprising: a) a first nucleic acid sequence encoding an antigen-binding domain that specifically binds to BCMA, wherein the first nucleic acid sequence comprises the sequence set forth in SEQ ID NO: 80; b) a second nucleic acid sequence encoding a transmembrane domain; and c) a third nucleic acid sequence encoding a costimulatorydomain. In some embodiments, the antigen-binding domain comprises a monospecific, bivalent VHH comprising a first heavy chain variable (VH) region and a second VH region each comprising a complementarity determining region 1 (VH CDR1), a VH CDR2, and VH CDR3 as set forth in the amino acid sequences of SEQ ID NO: 63, SEQ ID NO: 65, and SEQ ID NO: 67. In some embodiments, the first and / or the second VH region each comprise an amino acid sequence having at least 90%, 93%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO: 81, or wherein the first and / or the second VH region each comprises the amino acid sequence of SEQ ID NO: 81. In some embodiments, the first and / or the second VH region each comprise an amino acid sequence having at least 90%, 93%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO: 81, or wherein the first and / or the second VH region each comprises the amino acid sequence of SEQ ID NO: 81. In some embodiments, the first VH region comprises the amino acid sequence of SEQ ID NO: 81, and the second VH region comprises the amino acid sequence of SEQ ID NO: 81. In some embodiments, the bivalent VHH comprises a linker between the first and second VH regions. In some embodiments, the linker is a glycine-serine linker, e.g., a glycine-serine linker comprising the sequence of SEQ ID NO: 73. In some embodiments, the antigen-binding domain comprises the amino acid sequence of SEQ ID NO: 84. In some embodiments, the transmembrane domain comprises a CD8a transmembrane domain comprising an amino acid sequence of SEQ ID NO: 70. In some embodiments, the anti-BCMA CAR further comprises a hinge domain (e.g., a CD8a hinge domain, or fragment thereof, comprising an amino acid sequence of SEQ ID NO: 69) between the antigen-binding domain and the transmembrane domain. In some embodiments, the anti-BCMA CAR further comprises an activation domain, e.g., a CD3z activation domain comprising an amino acid sequence of SEQ ID NO: 72. In some embodiments, the anti-BCMA CAR comprises an amino acid sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 83. In some embodiments, the anti-BCMA CAR comprises the amino acid sequence of SEQ ID NO: 83. In some embodiments, the VH region is encoded by a nucleic acid sequence having at least 90%, 93%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO: 80 and the second VH region is encoded by a nucleic acid sequence having at least 90%, 93%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO: 80. In some embodiments, the anti-BCMA CAR is encoded by a nucleic acid sequence that is at least 95% identical to the nucleic acid sequence of SEQ ID NO: 82. The embodiments described herein provide exemplary nucleic acid sequences (e.g., SEQ ID NO: 80). It is understood that if a DNA sequence (comprising Ts) is referenced with respect to an RNA, then Ts should be replaced with Us (which may be modified or unmodified dependingon the context), and vice versa. Examples of modified U include, e.g., N1-methylpseudouridine, pseudouridine, 5-methoxy uridine, and 5-iodouridine.[000218] In some aspects, provided herein is a messenger RNA (mRNA) encoding an anti-BCMA CAR, comprising: a) a first nucleic acid sequence encoding an antigen-binding domain that specifically binds to BCMA, wherein the first nucleic acid sequence comprises the sequence set forth in SEQ ID NO: 80; b) a second nucleic acid sequence encoding a transmembrane domain; and c) a third nucleic acid sequence encoding a costimulatory domain, wherein the third nucleic acid sequence comprises the sequence set forth in SEQ ID NO: 11. In some embodiments, the antigen-binding domain comprises a monospecific, bivalent VHH comprising a first heavy chain variable (VH) region and a second VH region each comprising a complementarity determining region 1 (VH CDR1), a VH CDR2, and VH CDR3 as set forth in the amino acid sequences of SEQ ID NO: 63, SEQ ID NO: 65, and SEQ ID NO: 67. In some embodiments, the first and / or the second VH region each comprise an amino acid sequence having at least 90%, 93%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO: 81, or wherein the first and / or the second VH region each comprises the amino acid sequence of SEQ ID NO: 81. In some embodiments, the first VH region comprises the amino acid sequence of SEQ ID NO: 81, and the second VH region comprises the amino acid sequence of SEQ ID NO: 81. In some embodiments, the bivalent VHH comprises a linker between the first and second VH regions. In some embodiments, the linker is a glycine-serine linker, e.g., a glycine-serine linker comprises the sequence of SEQ ID NO: 73. In some embodiments, the antigen-binding domain comprises the amino acid sequence of SEQ ID NO: 84. In some embodiments, the transmembrane domain comprises a CD8a transmembrane domain comprising an amino acid sequence of SEQ ID NO: 70. In some embodiments, the anti-BCMA CAR further comprises a hinge domain (e.g., a CD8a hinge domain, or fragment thereof, comprising an amino acid sequence of SEQ ID NO: 69) between the antigen-binding domain and the transmembrane domain. In some embodiments, the anti-BCMA CAR further comprises an activation domain, e.g., a CD3z activation domain comprising an amino acid sequence of SEQ ID NO: 72. In some embodiments, the anti-BCMA CAR comprises an amino acid sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 83. In some embodiments, the anti-BCMA CAR comprises the amino acid sequence of SEQ ID NO: 83. In some embodiments, the VH region is encoded by a nucleic acid sequence having at least 90%, 93%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO: 80 and the second VH region is encoded by a nucleic acid sequence having at least 90%, 93%, 95%, 96%, 97%, 98%, or 99% identity toSEQ ID NO: 80. In some embodiments, the anti-BCMA CAR is encoded by a nucleic acid sequence that is at least 95% identical to the nucleic acid sequence of SEQ ID NO: 82. The embodiments described herein provide exemplary nucleic acid sequences (e.g., SEQ ID NO: 80). It is understood that if a DNA sequence (comprising Ts) is referenced with respect to an RNA, then Ts should be replaced with Us (which may be modified or unmodified depending on the context), and vice versa. Examples of modified U include, e.g., N1-methylpseudouridine, pseudouridine, 5-methoxy uridine, and 5-iodouridine.BCMA Binding Protein[000219] In some embodiments, the antigen binding domain of the encoded anti-BCMA CAR comprises an antibody, an antibody fragment, an scFv, a Fv, a Fab, a (Fab')2, a single domain antibody (SDAB), a VH or VL domain, a camelid VHH domain or a bi-functional (e.g., bispecific) hybrid antibody (e.g., Lanzavecchia et al., Eur. J. Immunol. 17, 105 (1987)).[000220] In some instances, scFvs can be prepared according to method known in the art (see, for example, Bird et al, (1988) Science 242:423-426 and Huston et al., (1988) Proc. Natl. Acad. Sci. USA 85:5879-5883). An example of an anti-BCMA CAR comprising an anti-BCMA scFv is described in FIG. 1 (see Benchmark 2A and Benchmark 2B).[000221] Bivalent VHH molecules can be produced by linking two VH and VH regions together using flexible polypeptide linkers. Bivalent VHH molecules comprise a linker (e.g., a Ser-Gly linker) with an optimized length and / or amino acid composition. The linker length can greatly affect how the variable regions of a VH fold and interact. For examples of linker orientation and size see, e.g., Hollinger et al. 1993 Proc Natl Acad. Sci. U. S. A. 90:6444-6448, U. S. Patent Application Publication Nos. 2005 / 0100543, 2005 / 0175606, 2007 / 0014794, and PCT publication Nos. W02006 / 020258 and W02007 / 024715, is incorporated herein by reference. Examples of anti-BCMA CARs comprising an anti-BCMA bivalent VHH are described in FIG. 1, e.g., Construct 2.[000222] A bivalent VHH can comprise a linker of at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 45, 50, or more amino acid residues between its two VH and VH regions. The linker sequence may comprise any naturally occurring amino acid. In some embodiments, the linker sequence comprises amino acids glycine and serine. In another embodiment, the linker sequence comprises sets of glycine and serine repeats such as (Gly4Ser)n, where n is a positive integer equal to or greater than 1. In one embodiment, the linker can be (Gly4Ser)3 (SEQ ID NO: 940). Variation in the linker length may retain or enhance activity, giving rise to superior efficacy in activity studies.[000223] In certain embodiments, the encoded antigen binding domain has a binding affinity KD of 10-4 M to 10-9 M. In one embodiment, the encoded CAR molecule comprises an antigen binding domain that has a binding affinity KD of 10-4 M to 10-9 M, e.g., 10-5 M to 10-7 M, e.g., 10-6 M or 10-7 M, e.g., 10-7 M to 10-8 M, e.g., 10-8 M to 10-9 M, for the target antigen.[000224] In one aspect, the antigen binding domain of an anti-BCMA CAR of the present disclosure (e.g., bivalent VHHs) is encoded by a nucleic acid molecule whose sequence has been codon optimized for expression in a mammalian cell. In one aspect, the entire anti-BCMA CAR construct of the present disclosure is encoded by a nucleic acid molecule whose entire sequence has been codon optimized for expression in a mammalian cell. Codon optimization refers to the discovery that the frequency of occurrence of synonymous codons (i.e., codons that code for the same amino acid) in coding DNA is biased in different species. Such codon degeneracy allows an identical polypeptide to be encoded by a variety of nucleotide sequences.[000225] In some embodiments, the present disclosure provides an anti-BCMA chimeric antigen receptor (CAR) comprising: (a) an antigen-binding domain that specifically binds to BCMA, wherein the antigen-binding domain comprises a monospecific, bivalent VHH comprising a first heavy chain variable (VH) region and a second VH region each comprising a complementarity determining region 1 (VH CDR1), a VH CDR2, and VH CDR3 as set forth in the amino acid sequences of SEQ ID NO: 63, SEQ ID NO: 65, and SEQ ID NO: 67, respectively; (b) a transmembrane domain; and (c) an intracellular domain comprising a costimulatory domain comprising an amino acid sequence of SEQ ID NO: 99 or 71.[000226] In some embodiments, the VH region comprises an amino acid sequence having at least 90%, 93%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO: 81. In some embodiments, the VH region comprises the amino acid sequence of SEQ ID NO: 81, with 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 substitutions in each of the VH CDR1, VH CDR2, and VH CDR3, independently.[000227] In some embodiments, the first VH region comprises the amino acid sequence of SEQ ID NO: 81, with 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 substitutions in each of the VH CDR1, VH CDR2, and VH CDR3, independently, and the second VH region comprises the amino acid sequence of SEQ ID NO: 81, with 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 substitutions in each of the VH CDR1, VH CDR2, and VH CDR3, independently.[000228] In some embodiments, the first VH region comprises the amino acid sequence of SEQ ID NO: 81, with 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 substitutions in the VH outside of theVH CDR1, VH CDR2, and VH CDR3, and the second VH region comprises the amino acid sequence of SEQ ID NO: 81, with 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 substitutions in the VH outside of the VH CDR1, VH CDR2, and VH CDR3 (i.e., the CDRs are unsubstituted).[000229] In some embodiments, the antigen-binding domain comprises an amino acid sequence of SEQ ID NO: 84, or a sequence having at least 90%, 93%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO: 84.[000230] In some embodiments, the antigen-binding domain comprises an amino acid sequence of SEQ ID NO: 81 or SEQ ID NO: 84 and the costimulatory domain comprises the amino acid sequence of SEQ ID NO: 99. In some embodiments, the antigen-binding domain comprises an amino acid sequence of SEQ ID NO: 81 and the costimulatory domain comprises the amino acid sequence of SEQ ID NO: 99. In some embodiments, the antigen-binding domain comprises an amino acid sequence of SEQ ID NO: 84 and the costimulatory domain comprises the amino acid sequence of SEQ ID NO: 99.[000231] In some embodiments, the antigen-binding domain comprises an amino acid sequence of SEQ ID NO: 81 or SEQ ID NO: 84 and the costimulatory domain comprises the amino acid sequence of SEQ ID NO: 71. In some embodiments, the antigen-binding domain comprises an amino acid sequence of SEQ ID NO: 81 and the costimulatory domain comprises the amino acid sequence of SEQ ID NO: 71. In some embodiments, the antigen-binding domain comprises an amino acid sequence of SEQ ID NO: 84 and the costimulatory domain comprises the amino acid sequence of SEQ ID NO: 71.[000232] In some embodiments, the transmembrane domain comprises a CD8a or CD28 transmembrane domain. In some embodiments, the transmembrane domain comprises a CD8a transmembrane domain comprising an amino acid sequence of SEQ ID NO: 95. In some embodiments, the transmembrane domain comprises a CD8a transmembrane region comprising an amino acid sequence having at least 90%, 93%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO: 95. In some embodiments, the transmembrane domain comprises a CD28 transmembrane domain comprising an amino acid sequence of SEQ ID NO: 93. In some embodiments, the transmembrane domain comprises a CD28 transmembrane domain having at least 90%, 93%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO: 93.[000233] In some embodiments, the anti-BCMA CAR further comprises a hinge domain between the antigen binding protein and the transmembrane domain. In some embodiments, the anti-BCMA CAR comprises a linker between the anti-BCMA binding protein (e.g., bivalent VHH) and the hinge domain. In some embodiments, the linker sequence is GlySer. In some embodiments, the hinge domain is a CD8a hinge domain. In some embodiments, the hingedomain is a CD8a hinge domain, or fragment thereof, comprising an amino acid sequence of SEQ ID NO: 89. In some embodiments, the hinge domain is a CD8a hinge domain, or fragment thereof, comprising an amino acid sequence having at least 90%, 93%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO: 89.[000234] In some embodiments, the intracellular domain further comprises an activation domain. In some embodiments, the activation domain is a CD3z activation domain comprising an amino acid sequence of SEQ ID NO: 103. In some embodiments, the hinge domain is a CD3z hinge domain comprising an amino acid sequence having at least 90%, 93%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO: 103.[000235] In some embodiments, the intracellular domain comprises a CD28 costimulatory domain comprising the amino acid sequence of SEQ ID NO: 99 and a CD3z activation domain comprising the amino acid sequence of SEQ ID NO: 103. In some embodiments, the intracellular domain comprises a 41BB costimulatory domain comprising the amino acid sequence of SEQ ID NO: 71 and a CD3z activation domain comprising the amino acid sequence of SEQ ID NO: 103.[000236] In some embodiments, the antigen-binding domain comprises a sequence of SEQ ID NO: 81 or 84 and the costimulatory domain comprises a sequence of SEQ ID NO: 71; the antigen-binding domain comprises a sequence of SEQ ID NO: 81 or 84 and the costimulatory domain comprises a sequence of SEQ ID NO: 99.[000237] In some embodiments, the anti-BCMA CAR comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of any one of SEQ ID NOs: 83, 231, 233, 235, 237, 239, 241, 243, 245, and 247. In one embodiment, the anti-BCMA CAR comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 83. In one embodiment, the anti-BCMA CAR comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 231. In one embodiment, the anti-BCMA CAR comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 233. In one embodiment, the anti-BCMA CAR comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 235. In one embodiment, the anti-BCMA CAR comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO:237. In one embodiment, the anti-BCMA CAR comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 239. In one embodiment, the anti-BCMA CAR comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 241. In one embodiment, the anti-BCMA CAR comprises an aminoacid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 243. In one embodiment, the anti-BCMA CAR comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 245. In one embodiment, the anti-BCMA CAR comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 247.[000238] In some embodiments, the antigen-binding domain is a VHH. In certain embodiments, the antigen binding protein is a monospecific bivalent VHH which comprises two VH regions that bind to the same epitope on BCMA.[000239] Preferably, the disclosed anti-BCMA CARs comprise a VHH comprising the CDR sequences corresponding to the heavy chain variable regions of an anti-BCMA VHH. Single chain antibodies may be formed by linking two heavy chain variable domains via an amino acid bridge (short peptide linker), resulting in a single polypeptide chain. Such VHHs have been prepared by fusing DNA encoding a peptide linker between DNAs encoding the two variable domain polypeptides (VH and VH). The resulting polypeptides can fold back on themselves to form antigen -binding monomers, or they can form multimers (e.g., dimers, trimers, or tetramers), depending on the length of a flexible linker between the two variable domains (Kortt et al., 1997, Prot. Eng. 10:423; Kortt et al., 2001, Biomol. Eng. 18:95-108). Techniques developed for the production of single chain antibodies include those described in U. S. Patent 4,946,778; Bird, 1988, Science 242:423; Huston et al., 1988, Proc. Natl. Acad. Sci. USA 85:5879; Ward et al., 1989, Nature 334:544, and de Graaf et al., 2002, Methods Mol. Biol. 178:379-87.[000240] Preferably, the disclosed anti-BCMA CARs comprise an antigen-binding domain comprising an amino acid sequence that is at least at least 90%, 93%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 83. In some embodiments, the antigen-binding domain comprises an amino acid sequence of SEQ ID NO: 83.Hinge Domains[000241] The anti-BCMA CARs described herein further comprise a hinge domain. The hinge domain is located between the antigen-binding region and the transmembrane domain. A hinge domain is an amino acid segment that is generally found between two domains of a protein, e.g., a human protein, and, in the context of anti-BCMA CARs, permits the movement of one or both of the antigen-binding region and transmembrane domain relative to each other. Preferably, the hinge domain comprises from about 10 to about 100 amino acids, e.g., from about 15 to about 75 amino acids, from about 20 to about 50 amino acids, orfrom about 30 to about 60 amino acids. In some embodiments, the hinge domain is a hinge domain of a naturally occurring protein.[000242] Preferably, the hinge domain used in a CAR is derived from CD8a. Preferably, the hinge domain of an anti-BCMA CAR comprises an amino acid sequence that is at least 90%, 93%, 95%, 96%, 97%, 98%, or 99% identical to an amino acid sequence of SEQ ID NO: 89. In some embodiments, the hinge domain comprises an amino acid sequence of SEQ ID NO: 89.[000243] Preferably, the hinge domain is positioned between the C-terminus of the bivalent VHH and the N-terminus of the transmembrane domain of the anti-BCMA CAR.Transmembrane Domains[000244] With respect to the transmembrane domain, in various embodiments, a CAR can be designed to comprise a transmembrane domain that is attached to the extracellular domain of the CAR. A transmembrane domain can include one or more additional amino acids adjacent to the transmembrane domain, e.g, one or more amino acid associated with the extracellular region of the protein from which the transmembrane domain was derived (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 up to 15 amino acids of the extracellular region) and / or one or more additional amino acids associated with the intracellular region of the protein from which the transmembrane protein is derived (e.g, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 up to 15 amino acids of the intracellular region). In one aspect, the transmembrane domain is one that is associated with one of the other domains of the CAR e.g., in one embodiment, the transmembrane domain may be from the same protein that the intracellular domain, costimulatory domain or the hinge domain is derived from. In another aspect, the transmembrane domain is not derived from the same protein that any other domain of the CAR is derived from. In some instances, the transmembrane domain can be selected or modified by amino acid substitution to avoid binding of such domains to the transmembrane domains of the same or different surface membrane proteins, e.g., to minimize interactions with other members of the receptor complex. In one aspect, the transmembrane domain is capable of homodimerization with another CAR on the cell surface of a CAR-expressing cell. In a different aspect, the amino acid sequence of the transmembrane domain may be modified or substituted so as to minimize interactions with the binding domains of the native binding partner present in the same CAR-expressing cell.[000245] The transmembrane domain may be derived either from a natural or from a recombinant source. Where the source is natural, the domain may be derived from anymembrane-bound or transmembrane protein. In one aspect the transmembrane domain is capable of signaling to the intracellular domain(s) whenever the CAR has bound to a target.[000246] In some embodiments, the transmembrane domain may be recombinant, in which case it will comprise predominantly hydrophobic residues such as leucine and valine. In one aspect a triplet of phenylalanine, tryptophan and valine can be found at each end of a recombinant transmembrane domain. Optionally, a short oligo- or polypeptide linker, between 2 and 10 amino acids in length may form the linkage between the transmembrane domain and the cytoplasmic region of the CAR. A glycine-serine doublet provides a particularly suitable linker.[000247] Preferably, the transmembrane domain used in a CAR is derived from a membrane protein selected from CD8a and CD28. Preferably, the transmembrane domain of an anti-BCMA CAR comprises an amino acid sequence that is at least 90%, 93%, 95%, 96%, 97%, 98%, or 99% identical to an amino acid sequence selected from SEQ ID NO: 93 and 95. In some embodiments, the transmembrane domain comprises an amino acid sequence of SEQ ID NO: 93 or 95.[000248] In some embodiments, the transmembrane domain is a CD8a transmembrane domain comprising an amino acid sequence of SEQ ID NO: 95. In some embodiments, the transmembrane domain is a CD28 transmembrane domain comprising an amino acid sequence of SEQ ID NO: 93.Intracellular domains[000249] In some embodiments of the present disclosure having an intracellular domain, e.g., an anti-BCMA CAR, such a domain can contain, e.g., one or more of an activation domain and / or a costimulatory domain. In some embodiments, the intracellular domain comprises a sequence encoding an activation domain. In some embodiments, the intracellular domain comprises a costimulatory domain. In some embodiments, the intracellular domain comprises an activation domain and a costimulatory domain.[000250] The intracellular domain sequences within the cytoplasmic portion of the anti-BCMA CAR of the present disclosure may be linked to each other in a random or specified order. Optionally, a short oligo- or polypeptide linker, for example, between 2 and 10 amino acids (e.g., 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acids) in length may form the linkage between intracellular signaling sequences. In one embodiment, a glycine-serine doublet can be used as a suitable linker. In one embodiment, a single amino acid, e.g., an alanine, a glycine, can be used as a suitable linker.[000251] In one aspect, the intracellular domain is designed to comprise two or more, e.g., 2, 3, 4, 5, or more, costimulatory domains. In an embodiment, the two or more, e.g., 2, 3, 4, 5, or more, costimulatory domains, are separated by a linker molecule, e.g., a linker molecule described herein. In one embodiment, the intracellular domain comprises two costimulatory domains. In some embodiments, the linker molecule is a glycine residue. In some embodiments, the linker is an alanine residue. / . Activation domain[000252] In some embodiments, the disclosed anti-BCMA CARs comprise an intracellular activation domain. The activation domain is generally responsible for activation of at least one of the normal effector functions of a cell. The term “effector function” describes a specialized function of a cell. For example, the effector function of a T-cell or an NK cell includes a cytolytic activity or helper activity. “Activation domain” describes the portion of a protein which transduces the effector function signal and directs the cell to perform its specialized function. While the entire activation domain can be employed, in many cases it is not necessary to use an entire chain or domain. To the extent that a truncated portion of the activation domain is used, such truncated portion may be used in place of the intact domain as long as it transduces the effector function signal.[000253] An activation domain promotes the activation of the TCR complex. Activation domains may contain signaling motifs which are known as immunoreceptor tyrosine-based activation motifs (ITAMs). Activation domains containing ITAMs for use in the anti-BCMA CARs include the intracellular domains of TCR zeta, FcR gamma, FcR beta, CD3 gamma, CD3 delta, CD3 epsilon, CD5, CD22, CD79a, CD79b, and CD66d. Preferably, an activation domain is CD3^> or CD28.[000254] Preferably, the activation domain used in a CAR is derived from a membrane protein selected from CD3z. Preferably, the activation domain of an anti-BCMA CAR comprises an amino acid sequence that is at least 90%, 93%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 103. In some embodiments, the activation domain comprises an amino acid sequence of SEQ ID NO: 103.[000255] In some embodiments, the intracellular domain comprises an activation domain, or a functional fragment thereof, the activation domain is a CD3z activation domain comprising an amino acid sequence of SEQ ID NO: 103.2. Costimulatory domain[000256] In some embodiments, the disclosed anti-BCMA CARs comprise a costimulatory domain. Examples of costimulatory domains for use in the chimeric receptors are cytoplasmic signaling domain of costimulatory proteins selected from the group consisting of members of the B7 / CD28 family (B7-1 / CD80, B7-2 / CD86, B7-H1 / PD-L1, B7-H2, B7-H3, B7-H4, B7-H6, B7-H7, BTLA / CD272, CD28, CTLA-4, Gi24 / VISTA / B7-H5, ICOS / CD278, PD-1, PD-L2 / B7-DC, and PDCD6); members of the TNF superfamily (4-1BB / TNFSF9 / CD137, 4-1BB ligand / TNFSF9, BAFF / BLyS / TNFSF13B, BAFF R / TNFRSF13C, CD27 / TNFRSF7, CD27 ligand / TNFSF7, CD30 / TNFRSF8, CD30 ligand / TNFSF8, CD40 / TNFRSF5, CD40 / TNFSF5, CD40 ligand / TNFSF5, DR3 / TNFRSF25, GITR / TNFRSF18, GITR ligand / TNFSF18, HVEM / TNFRSF14, LIGHT / TNFSF14, lymphotoxin-alpha / TNF-beta, OX40 / TNFRSF4, 0X40 ligand / TNFSF4, RELT / TNFRSF19L, TACI / TNFRSF13B, TL1A / TNFSF15, TNF-a, and TNF RII / TNFRSF1B); members of the interleukin-1 receptor / toll-like receptor (TLR) superfamily (TLR1, TLR2, TLR3, TLR4, TLR5, TLR6, TLR7, TLR8, TLR9, and TLR10); members of the SLAM family (2B4 / CD244 / SLAMF4, BLAME / SLAMF8, CD2, CD2F-10 / SLAMF9, CD48 / SLAMF2, CD58 / LFA-3, CD84 / SLAMF5, CD229 / SLAMF3, CRACC / SLAMF7, NTB-A / SLAMF6, and SLAM / CD150); CD2, CD7, CD53, CD82 / Kai-1, CD90 / Thyl, CD96, CD160, CD200, CD300a / LMIRl, HLA Class I, HLA-DR, ikaros, integrin alpha 4 / CD49d, integrin alpha 4 beta 1, integrin alpha 4 beta 7 / LPAM-l, LAG-3, TCL1A, TCL1B, CRTAM, DAP10, DAP12, MYD88, TRIF, TIRAP, TRAF, Dectin- 1 / CLEC7 A, DPPIV / CD26, EphB6, TIM-l / KIM-1 / HAVCR, TIM-4, TSLP, TSLP R, lymphocyte function associated antigen-1 (LFA-1), and NKG2C. Preferably, the costimulatory domain comprises an intracellular domain of an activating receptor protein selected from the group consisting of α4β1 integrin, β2 integrins (CDlla-CD18, CDllb-CD18, CDllb-CD18), CD226, CRTAM, CD27, NKp46, CD 16, NKp30, NKp44, NKp80, NKG2D, KIR-S, CD 100, CD94 / NKG2C, CD94 / NKG2E, NKG2D, PEN5, CEACAM1, BY55, CRACC, Ly9, CD84, NTBA, 2B4, SAP, DAP10, DAP12, EAT2, FcRy, CD3ζ, and ERT. Preferably, the costimulatory domain comprises an intracellular domain of an inhibitory receptor protein selected from the group consisting of KIR-L, LILRB1, CD94 / NKG2A, KLRG-1, NKR-P1A, TIGIT, CEACAM, SIGLEC 3, SIGLEC 7, SIGLEC9, and LAIR-1. Preferably, the costimulatory domain comprises an intracellular domain of a protein selected from the group consisting of CD27, CD28, 4-1BB (CD137),0X40, CD30, CD40, PD1, ICOS, lymphocyte function-associated antigen-1 (LFA-1), CD2, CD7, LIGHT, NKG2C, B7-H3, and a ligand that specifically binds with CD83.[000257] Preferably, the costimulatory domain of the anti-BCMA CAR disclosed herein is derived from a membrane protein selected from 4-1BB and CD28. Preferably, the costimulatory domain of an anti-BCMA CAR comprises an amino acid sequence that is at least 90%, 93%, 95%, 96%, 97%, 98%, or 99% identical to an amino acid sequence of SEQ ID NO: 99 or 71. In some embodiments, the costimulatory domain comprises an amino acid sequence of SEQ ID NO: 99 or 71. In some embodiments, the costimulatory domain of the CAR disclosed herein comprises a costimulatory domain of 4- IBB. In some embodiments, the costimulatory domain of the CAR disclosed herein comprises a costimulatory domain of CD28.[000258] In some embodiments, the intracellular domain comprises a costimulatory domain, or a functional fragment thereof, the costimulatory domain is a 4-1BB or CD28 costimulatory domain. In some embodiments, the costimulatory domain is a 4-1BB costimulatory domain comprising an amino acid sequence of SEQ ID NO: 71. In some embodiments, the costimulatory domain is a CD28 costimulatory domain comprising an amino acid sequence of SEQ ID NO: 99.Vectors Comprising Anti-BCMA CARs[000259] In another aspect, the present disclosure pertains to a vector comprising a nucleic acid sequence encoding an anti-BCMA CAR described herein. In one embodiment, the vector is chosen from a DNA vector, an RNA vector, a plasmid, a lentivirus vector, adenoviral vector, and a retrovirus vector. In one embodiment, the vector is a lentivirus vector. These vectors or portions thereof may, among other things, be used to create template nucleic acids, as described herein for use with the CRISPR systems as described herein. Alternatively, the vectors may be used to deliver nucleic acid directly to the cell, e.g., the immune effector cell, e.g., the T-cell, e.g., the allogeneic T-cell, independent of the CRISPR system.[000260] The present disclosure also provides vectors in which a DNA of the present disclosure is inserted. Vectors derived from retroviruses such as the lentivirus are suitable tools to achieve long-term gene transfer since they allow long-term, stable integration of a transgene and its propagation in daughter cells. Lentiviral vectors have the added advantage over vectors derived from onco-retroviruses such as murine leukemia viruses in that they can transduce non-proliferating cells, such as hepatocytes. They also have the added advantage of low immunogenicity. A retroviral vector may also be, e.g., a gammaretroviral vector. Agammaretroviral vector may include, e.g., a promoter, a packaging signal (ψ), a primer binding site (PBS), one or more e.g., two) long terminal repeats (LTR), and a transgene of interest, e.g., a gene encoding a CAR. A gammaretroviral vector may lack viral structural gens such as gag, pol, and env. Exemplary gammaretroviral vectors include Murine Leukemia Virus (MLV), Spleen-Focus Forming Virus (SFFV), and Myeloproliferative Sarcoma Virus (MPSV), and vectors derived therefrom. Other gammaretroviral vectors are described, e.g., in Tobias Maetzig et al., " Gammaretroviral Vectors: Biology, Technology and Application" Viruses. 2011 Jun; 3(6): 677-713.[000261] In certain embodiments, a vector described herein comprises the DNA sequence set forth in SEQ ID NO: 82, 230, 232, 234, 236, 238, 240, 242, 244, or 246.[000262] In certain embodiments, a vector described herein comprises a DNA sequence encoding an anti-BCMA CAR as set forth in SEQ ID NO: 83, 231, 233, 235, 237, 239, 241, 243, 245, or 247.[000263] In another embodiment, the vector comprising the nucleic acid encoding the desired anti-BCMA CAR of the present disclosure is an adenoviral vector (A5 / 35). In another embodiment, the expression of nucleic acids encoding anti-BCMA CARs can be accomplished using of transposons such as sleeping beauty, crisper, CAS9, and zinc finger nucleases. See below June etal. 2009Nature Reviews Immunology 9.10: 704-716, is incorporated herein by reference.[000264] The nucleic acid can be cloned into a number of types of vectors. For example, the nucleic acid can be cloned into a vector including, but not limited to a plasmid, a phagemid, a phage derivative, an animal virus, and a cosmid. Vectors of particular interest include expression vectors, replication vectors, probe generation vectors, and sequencing vectors.[000265] Disclosed herein are methods for producing an in vitro transcribed RNA encoding an anti-BCMA CAR. The present disclosure also includes a CAR encoding RNA construct that can be directly transfected into a cell. A method for generating mRNA for use in transfection can involve in vitro transcription (IVT) of a template with specially designed primers, followed by polyA addition, to produce a construct containing 3' and 5' untranslated sequence (" UTR"), a 5' cap and / or Internal Ribosome Entry Site (IRES), the nucleic acid to be expressed, and a poly-A tail, typically 50-2000 bases in length. RNA so produced can efficiently transfect different kinds of cells. In one aspect, the template includes sequences for an anti-BCMA CAR described herein.III. Genetically Modified Cells Comprising Anti-BCMA Chimeric Antigen Receptors (CARs) and Reduced or Eliminated Surface Expression of One or More of HLA-A, HLA-B, TRAC, MHC Class II, and TGFBR2Engineered Cell Compositions[000266] In another aspect, the present disclosure provides for engineered cells or cell populations comprising an anti-BCMA CAR, e.g., an anti-BCMA CAR as described in Section II. In some embodiments, the cell is engineered to express an anti-BCMA CAR, e.g., as described herein. In some embodiments, the anti-BCMA CAR-engineered cell is allogeneic. In embodiments, the anti-BCMA CAR-engineered cell is autologous.[000267] In some embodiments, the present disclosure provides an engineered cell or cell populations, engineered to express an anti-BCMA chimeric antigen receptor (CAR) comprising: (a) an antigen-binding domain that specifically binds to BCMA, wherein the antigen-binding domain comprises a monospecific, bivalent VHH comprising a first heavy chain variable (VH) region and a second VH region each comprising a complementarity determining region 1 (VH CDR1), a VH CDR2, and VH CDR3 as set forth in the amino acid sequences of SEQ ID NO: 63, SEQ ID NO: 65, and SEQ ID NO: 67, respectively; (b) a transmembrane domain; and (c) an intracellular domain comprising a costimulatory domain comprising an amino acid sequence of SEQ ID NO: 99 or 71.[000268] In some embodiments, the VH region comprises an amino acid sequence having at least 90%, 93%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO: 81. In some embodiments, the VH region comprises the amino acid sequence of SEQ ID NO: 81, with 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 substitutions in each of the VH CDR1, VH CDR2, and VH CDR3, independently. In some embodiments, the VH region comprises an amino acid sequence of SEQ ID NO: 81. It is contemplated the first and / or the second VH region comprises any combination of the foregoing variations of SEQ ID NO: 81, where the first and second VH regions of the anti-BCMA monospecific bivalent VHH are the same or alternatively have different sequences based on the foregoing variations of SEQ ID NO: 81.[000269] Aspects of the present disclosure include engineered cells, e.g., CAR-T cells, comprising means for binding to the binding targets described herein, namely, BCMA. In some embodiments, a CAR-T cell comprises an antigen-binding domain comprising means for binding to BCMA. CAR-T cells comprising antigen-binding domains comprising means for binding to a binding target (i.e., BCMA) include equivalents of the structural features of the antigen-binding domains described herein, for example, equivalents of the BCMA binding domains described herein.[000270] In some embodiments, the antigen-binding domain comprises an amino acid sequence of SEQ ID NO: 81 or SEQ ID NO: 84 and the costimulatory domain comprises the amino acid sequence of SEQ ID NO: 99. In some embodiments, the antigen-binding domain comprises an amino acid sequence of SEQ ID NO: 81 and the costimulatory domain comprises the amino acid sequence of SEQ ID NO: 99. In some embodiments, the antigen-binding domain comprises an amino acid sequence of SEQ ID NO: 84 and the costimulatory domain comprises the amino acid sequence of SEQ ID NO: 99.[000271] In some embodiments, the antigen-binding domain comprises an amino acid sequence of SEQ ID NO: 81 or SEQ ID NO: 84 and the costimulatory domain comprises the amino acid sequence of SEQ ID NO: 71. In some embodiments, the antigen-binding domain comprises an amino acid sequence of SEQ ID NO:815 and the costimulatory domain comprises the amino acid sequence of SEQ ID NO: 71. In some embodiments, the antigen-binding domain comprises an amino acid sequence of SEQ ID NO: 84 and the costimulatory domain comprises the amino acid sequence of SEQ ID NO: 71.[000272] In some embodiments, the transmembrane domain comprises a CD8a or CD28 transmembrane domain. In some embodiments, the transmembrane domain comprises a CD8a transmembrane domain comprising an amino acid sequence of SEQ ID NO: 95. In some embodiments, the transmembrane domain comprises a CD8a transmembrane domain having at least 90%, 93%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO: 95. In some embodiments, the transmembrane domain comprises a CD28 transmembrane region comprising an amino acid sequence of SEQ ID NO: 93. In some embodiments, the transmembrane domain comprises a CD28 domain having at least 90%, 93%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO: 93.[000273] In some embodiments, the anti-BCMA CAR further comprises a hinge domain between the antigen binding protein and the transmembrane domain. In some embodiments, the hinge domain is a CD8a hinge domain. In some embodiments, the hinge domain is a CD8a hinge domain comprising an amino acid sequence of SEQ ID NO: 89. In some embodiments, the hinge domain is a CD8a hinge domain comprising an amino acid sequence having at least 90%, 93%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO: 89.[000274] In some embodiments, the intracellular domain further comprises an activation domain. In some embodiments, the activation domain is a CD3z activation domain comprising an amino acid sequence of SEQ ID NO: 103. In some embodiments, the hinge domain is a CD3z hinge domain comprising an amino acid sequence having at least 90%, 93%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO: 103.[000275] In some embodiments, the intracellular domain comprises a CD28 costimulatory domain comprising the amino acid sequence of SEQ ID NO: 99 and a CD3z activation domain comprising the amino acid sequence of SEQ ID NO: 103. In some embodiments, the intracellular domain comprises a 41BB costimulatory domain comprising the amino acid sequence of SEQ ID NO: 71 and a CD3z activation domain comprising the amino acid sequence of SEQ ID NO: 103.[000276] In some embodiments, the anti-BCMA CAR comprises a sequence of SEQ ID NO: 84 and the costimulatory domain comprises a sequence of SEQ ID NO: 71; the antigenbinding domain comprises a sequence of SEQ ID NO: 84 and the costimulatory domain comprises a sequence of SEQ ID NO: 99.[000277] In some embodiments, the anti-BCMA CAR comprises a sequence of SEQ ID NO: 81 and the costimulatory domain comprises a sequence of SEQ ID NO: 71; the antigenbinding domain comprises a sequence of SEQ ID NO: 81 and the costimulatory domain comprises a sequence of SEQ ID NO: 99.[000278] In some embodiments, the anti-BCMA CAR comprises an amino acid sequence that is at least 90% identical to the amino acid sequence of any one of SEQ ID NOs: 83, 231, 233, 235, 237, 239, 241, 243, 245, or 247. In some embodiments, the anti-BCMA CAR comprises an amino acid sequence that is at least 91% identical to the amino acid sequence of any one of SEQ ID NOs: 83, 231, 233, 235, 237, 239, 241, 243, 245, or 247. In some embodiments, the anti-BCMA CAR comprises an amino acid sequence that is at least 92% identical to the amino acid sequence of any one of SEQ ID NOs: 83, 231, 233, 235, 237, 239, 241, 243, 245, or 247. In some embodiments, the anti-BCMA CAR comprises an amino acid sequence that is at least 93% identical to the amino acid sequence of any one of SEQ ID NOs: 83, 231, 233, 235, 237, 239, 241, 243, 245, or 247. In some embodiments, the anti-BCMA CAR comprises an amino acid sequence that is at least 94% identical to the amino acid sequence of any one of SEQ ID NOs: 83, 231, 233, 235, 237, 239, 241, 243, 245, or 247. In some embodiments, the anti-BCMA CAR comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of any one of SEQ ID NOs: 83, 231, 233, 235, 237, 239, 241, 243, 245, or 247. In some embodiments, the anti-BCMA CAR comprises an amino acid sequence that is at least 96% identical to the amino acid sequence of any one of SEQ ID NOs: 83, 231, 233, 235, 237, 239, 241, 243, 245, or 247. In some embodiments, the anti-BCMA CAR comprises an amino acid sequence that is at least 97% identical to the amino acid sequence of any one of SEQ ID NOs: 83, 231, 233, 235, 237, 239, 241, 243, 245, or 247. In some embodiments, the anti-BCMA CAR comprises an amino acid sequence that is at least98% identical to the amino acid sequence of any one of SEQ ID NOs: 83, 231, 233, 235, 237, 239, 241, 243, 245, or 247. In some embodiments, the anti-BCMA CAR comprises an amino acid sequence that is at least 99% identical to the amino acid sequence of any one of SEQ ID NOs: 83, 231, 233, 235, 237, 239, 241, 243, 245, or 247. In some embodiments, the anti-BCMA CAR comprises the amino acid sequence of any one of SEQ ID NOs: 83, 231, 233, 235, 237, 239, 241, 243, 245, or 247.[000279] In one embodiment, the anti-BCMA CAR comprises an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 83. In one embodiment, the anti-BCMA CAR comprises an amino acid sequence that is at least 91% identical to the amino acid sequence of SEQ ID NO: 83. In one embodiment, the anti-BCMA CAR comprises an amino acid sequence that is at least 92% identical to the amino acid sequence of SEQ ID NO: 83. In one embodiment, the anti-BCMA CAR comprises an amino acid sequence that is at least 93% identical to the amino acid sequence of SEQ ID NO: 83. In one embodiment, the anti-BCMA CAR comprises an amino acid sequence that is at least 94% identical to the amino acid sequence of SEQ ID NO: 83. In one embodiment, the anti-BCMA CAR comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 83. In one embodiment, the anti-BCMA CAR comprises an amino acid sequence that is at least 96% identical to the amino acid sequence of SEQ ID NO: 83. In one embodiment, the anti-BCMA CAR comprises an amino acid sequence that is at least 97% identical to the amino acid sequence of SEQ ID NO: 83. In one embodiment, the anti-BCMA CAR comprises an amino acid sequence that is at least 98% identical to the amino acid sequence of SEQ ID NO: 83. In one embodiment, the anti-BCMA CAR comprises an amino acid sequence that is at least 99% identical to the amino acid sequence of SEQ ID NO: 83. In one embodiment, the anti-BCMA CAR comprises the amino acid sequence of SEQ ID NO: 83.[000280] In one embodiment, the anti-BCMA CAR comprises an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 231. In one embodiment, the anti-BCMA CAR comprises an amino acid sequence that is at least 91% identical to the amino acid sequence of SEQ ID NO: 231. In one embodiment, the anti-BCMA CAR comprises an amino acid sequence that is at least 92% identical to the amino acid sequence of SEQ ID NO: 231. In one embodiment, the anti-BCMA CAR comprises an amino acid sequence that is at least 93% identical to the amino acid sequence of SEQ ID NO: 231. In one embodiment, the anti-BCMA CAR comprises an amino acid sequence that is at least 94% identical to the amino acid sequence of SEQ ID NO: 231. In one embodiment, the anti-BCMA CAR comprises an amino acid sequence that is at least 95% identical to the amino acidsequence of SEQ ID NO: 231. In one embodiment, the anti-BCMA CAR comprises an amino acid sequence that is at least 96% identical to the amino acid sequence of SEQ ID NO: 231. In one embodiment, the anti-BCMA CAR comprises an amino acid sequence that is at least 97% identical to the amino acid sequence of SEQ ID NO: 231. In one embodiment, the anti-BCMA CAR comprises an amino acid sequence that is at least 98% identical to the amino acid sequence of SEQ ID NO: 231. In one embodiment, the anti-BCMA CAR comprises an amino acid sequence that is at least 99% identical to the amino acid sequence of SEQ ID NO: 231. In one embodiment, the anti-BCMA CAR comprises the amino acid sequence of SEQ ID NO: 231.[000281] In one embodiment, the anti-BCMA CAR comprises an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 233. In one embodiment, the anti-BCMA CAR comprises an amino acid sequence that is at least 91% identical to the amino acid sequence of SEQ ID NO: 233. In one embodiment, the anti-BCMA CAR comprises an amino acid sequence that is at least 92% identical to the amino acid sequence of SEQ ID NO: 233. In one embodiment, the anti-BCMA CAR comprises an amino acid sequence that is at least 93% identical to the amino acid sequence of SEQ ID NO: 233. In one embodiment, the anti-BCMA CAR comprises an amino acid sequence that is at least 94% identical to the amino acid sequence of SEQ ID NO: 233. In one embodiment, the anti-BCMA CAR comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 233. In one embodiment, the anti-BCMA CAR comprises an amino acid sequence that is at least 96% identical to the amino acid sequence of SEQ ID NO: 231. In one embodiment, the anti-BCMA CAR comprises an amino acid sequence that is at least 97% identical to the amino acid sequence of SEQ ID NO: 233. In one embodiment, the anti-BCMA CAR comprises an amino acid sequence that is at least 98% identical to the amino acid sequence of SEQ ID NO: 233. In one embodiment, the anti-BCMA CAR comprises an amino acid sequence that is at least 99% identical to the amino acid sequence of SEQ ID NO: 233. In one embodiment, the anti-BCMA CAR comprises the amino acid sequence of SEQ ID NO: 233.[000282] In one embodiment, the anti-BCMA CAR comprises an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 235. In one embodiment, the anti-BCMA CAR comprises an amino acid sequence that is at least 91% identical to the amino acid sequence of SEQ ID NO: 235. In one embodiment, the anti-BCMA CAR comprises an amino acid sequence that is at least 92% identical to the amino acid sequence of SEQ ID NO: 235. In one embodiment, the anti-BCMA CAR comprises an aminoacid sequence that is at least 93% identical to the amino acid sequence of SEQ ID NO: 235. In one embodiment, the anti-BCMA CAR comprises an amino acid sequence that is at least 94% identical to the amino acid sequence of SEQ ID NO: 235. In one embodiment, the anti-BCMA CAR comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 235. In one embodiment, the anti-BCMA CAR comprises an amino acid sequence that is at least 96% identical to the amino acid sequence of SEQ ID NO: 235. In one embodiment, the anti-BCMA CAR comprises an amino acid sequence that is at least 97% identical to the amino acid sequence of SEQ ID NO: 235. In one embodiment, the anti-BCMA CAR comprises an amino acid sequence that is at least 98% identical to the amino acid sequence of SEQ ID NO: 235. In one embodiment, the anti-BCMA CAR comprises an amino acid sequence that is at least 99% identical to the amino acid sequence of SEQ ID NO: 235. In one embodiment, the anti-BCMA CAR comprises the amino acid sequence of SEQ ID NO: 235.[000283] In one embodiment, the anti-BCMA CAR comprises an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 237. In one embodiment, the anti-BCMA CAR comprises an amino acid sequence that is at least 91% identical to the amino acid sequence of SEQ ID NO: 237. In one embodiment, the anti-BCMA CAR comprises an amino acid sequence that is at least 92% identical to the amino acid sequence of SEQ ID NO: 237. In one embodiment, the anti-BCMA CAR comprises an amino acid sequence that is at least 93% identical to the amino acid sequence of SEQ ID NO: 237. In one embodiment, the anti-BCMA CAR comprises an amino acid sequence that is at least 94% identical to the amino acid sequence of SEQ ID NO: 237. In one embodiment, the anti-BCMA CAR comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 237. In one embodiment, the anti-BCMA CAR comprises an amino acid sequence that is at least 96% identical to the amino acid sequence of SEQ ID NO: 237. In one embodiment, the anti-BCMA CAR comprises an amino acid sequence that is at least 97% identical to the amino acid sequence of SEQ ID NO: 237. In one embodiment, the anti-BCMA CAR comprises an amino acid sequence that is at least 98% identical to the amino acid sequence of SEQ ID NO: 237. In one embodiment, the anti-BCMA CAR comprises an amino acid sequence that is at least 99% identical to the amino acid sequence of SEQ ID NO: 237. In one embodiment, the anti-BCMA CAR comprises the amino acid sequence of SEQ ID NO: 237.[000284] In one embodiment, the anti-BCMA CAR comprises an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 239. In oneembodiment, the anti-BCMA CAR comprises an amino acid sequence that is at least 91% identical to the amino acid sequence of SEQ ID NO: 239. In one embodiment, the anti-BCMA CAR comprises an amino acid sequence that is at least 92% identical to the amino acid sequence of SEQ ID NO: 239. In one embodiment, the anti-BCMA CAR comprises an amino acid sequence that is at least 93% identical to the amino acid sequence of SEQ ID NO: 239. In one embodiment, the anti-BCMA CAR comprises an amino acid sequence that is at least 94% identical to the amino acid sequence of SEQ ID NO: 239. In one embodiment, the anti-BCMA CAR comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 239. In one embodiment, the anti-BCMA CAR comprises an amino acid sequence that is at least 96% identical to the amino acid sequence of SEQ ID NO: 239. In one embodiment, the anti-BCMA CAR comprises an amino acid sequence that is at least 97% identical to the amino acid sequence of SEQ ID NO: 239. In one embodiment, the anti-BCMA CAR comprises an amino acid sequence that is at least 98% identical to the amino acid sequence of SEQ ID NO: 239. In one embodiment, the anti-BCMA CAR comprises an amino acid sequence that is at least 99% identical to the amino acid sequence of SEQ ID NO: 239. In one embodiment, the anti-BCMA CAR comprises the amino acid sequence of SEQ ID NO: 239.[000285] In one embodiment, the anti-BCMA CAR comprises an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 241. In one embodiment, the anti-BCMA CAR comprises an amino acid sequence that is at least 91% identical to the amino acid sequence of SEQ ID NO: 241. In one embodiment, the anti-BCMA CAR comprises an amino acid sequence that is at least 92% identical to the amino acid sequence of SEQ ID NO: 241. In one embodiment, the anti-BCMA CAR comprises an amino acid sequence that is at least 93% identical to the amino acid sequence of SEQ ID NO: 241. In one embodiment, the anti-BCMA CAR comprises an amino acid sequence that is at least 94% identical to the amino acid sequence of SEQ ID NO: 241. In one embodiment, the anti-BCMA CAR comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 241. In one embodiment, the anti-BCMA CAR comprises an amino acid sequence that is at least 96% identical to the amino acid sequence of SEQ ID NO: 241. In one embodiment, the anti-BCMA CAR comprises an amino acid sequence that is at least 97% identical to the amino acid sequence of SEQ ID NO: 241. In one embodiment, the anti-BCMA CAR comprises an amino acid sequence that is at least 98% identical to the amino acid sequence of SEQ ID NO: 241. In one embodiment, the anti-BCMA CAR comprises an amino acid sequence that is at least 99% identical to the amino acid sequence of SEQ ID NO: 241. Inone embodiment, the anti-BCMA CAR comprises the amino acid sequence of SEQ ID NO: 241.[000286] In one embodiment, the anti-BCMA CAR comprises an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 243. In one embodiment, the anti-BCMA CAR comprises an amino acid sequence that is at least 91% identical to the amino acid sequence of SEQ ID NO: 243. In one embodiment, the anti-BCMA CAR comprises an amino acid sequence that is at least 92% identical to the amino acid sequence of SEQ ID NO: 243. In one embodiment, the anti-BCMA CAR comprises an amino acid sequence that is at least 93% identical to the amino acid sequence of SEQ ID NO: 243. In one embodiment, the anti-BCMA CAR comprises an amino acid sequence that is at least 94% identical to the amino acid sequence of SEQ ID NO: 243. In one embodiment, the anti-BCMA CAR comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 243. In one embodiment, the anti-BCMA CAR comprises an amino acid sequence that is at least 96% identical to the amino acid sequence of SEQ ID NO: 243. In one embodiment, the anti-BCMA CAR comprises an amino acid sequence that is at least 97% identical to the amino acid sequence of SEQ ID NO: 243. In one embodiment, the anti-BCMA CAR comprises an amino acid sequence that is at least 98% identical to the amino acid sequence of SEQ ID NO: 243. In one embodiment, the anti-BCMA CAR comprises an amino acid sequence that is at least 99% identical to the amino acid sequence of SEQ ID NO: 243. In one embodiment, the anti-BCMA CAR comprises the amino acid sequence of SEQ ID NO: 243.[000287] In one embodiment, the anti-BCMA CAR comprises an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 245. In one embodiment, the anti-BCMA CAR comprises an amino acid sequence that is at least 91% identical to the amino acid sequence of SEQ ID NO: 245. In one embodiment, the anti-BCMA CAR comprises an amino acid sequence that is at least 92% identical to the amino acid sequence of SEQ ID NO: 245. In one embodiment, the anti-BCMA CAR comprises an amino acid sequence that is at least 93% identical to the amino acid sequence of SEQ ID NO: 245. In one embodiment, the anti-BCMA CAR comprises an amino acid sequence that is at least 94% identical to the amino acid sequence of SEQ ID NO: 245. In one embodiment, the anti-BCMA CAR comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 245. In one embodiment, the anti-BCMA CAR comprises an amino acid sequence that is at least 96% identical to the amino acid sequence of SEQ ID NO: 245. In one embodiment, the anti-BCMA CAR comprises an amino acid sequence that is at least 97%identical to the amino acid sequence of SEQ ID NO: 245. In one embodiment, the anti-BCMA CAR comprises an amino acid sequence that is at least 98% identical to the amino acid sequence of SEQ ID NO: 245. In one embodiment, the anti-BCMA CAR comprises an amino acid sequence that is at least 99% identical to the amino acid sequence of SEQ ID NO: 245. In one embodiment, the anti-BCMA CAR comprises the amino acid sequence of SEQ ID NO: 245.[000288] In one embodiment, the anti-BCMA CAR comprises an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 247. In one embodiment, the anti-BCMA CAR comprises an amino acid sequence that is at least 91% identical to the amino acid sequence of SEQ ID NO: 247. In one embodiment, the anti-BCMA CAR comprises an amino acid sequence that is at least 92% identical to the amino acid sequence of SEQ ID NO: 247. In one embodiment, the anti-BCMA CAR comprises an amino acid sequence that is at least 93% identical to the amino acid sequence of SEQ ID NO: 247. In one embodiment, the anti-BCMA CAR comprises an amino acid sequence that is at least 94% identical to the amino acid sequence of SEQ ID NO: 247. In one embodiment, the anti-BCMA CAR comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 247. In one embodiment, the anti-BCMA CAR comprises an amino acid sequence that is at least 96% identical to the amino acid sequence of SEQ ID NO: 247. In one embodiment, the anti-BCMA CAR comprises an amino acid sequence that is at least 97% identical to the amino acid sequence of SEQ ID NO: 247. In one embodiment, the anti-BCMA CAR comprises an amino acid sequence that is at least 98% identical to the amino acid sequence of SEQ ID NO: 247. In one embodiment, the anti-BCMA CAR comprises an amino acid sequence that is at least 99% identical to the amino acid sequence of SEQ ID NO: 247. In one embodiment, the anti-BCMA CAR comprises the amino acid sequence of SEQ ID NO: 247.[000289] In some embodiments, the antigen-binding domain is a VHH, e.g., a bivalent VHH.[000290] In some embodiments, the present disclosure provides for a population of cells, wherein the cell is the engineered cell of the present disclosure.[000291] In some aspects, the cells or cell population of the current disclosure further comprise, a gRNA molecule, e.g., one or more gRNA molecules, as described herein, or a CRISPR system as described herein or comprise a genetic modification within genomic coordinates targeted by a guide RNA or CRISPR system as described herein. In an embodiment, the cell is further altered, e.g., the target sequence targeted by the gRNA molecule is further altered, e.g., to create an indel, or a base conversion, by introduction of agRNA molecule as described herein (or nucleic acid encoding said gRNA molecule), or a CRISPR system (or nucleic acid encoding one or more components of said CRISPR system) as described herein, e.g., altered by a method described herein. In an embodiment, the alteration results in reduced or no expression of the functional (e.g., wild type) gene product of the gene comprising the target site.[000292] In one aspect, the cell is an animal cell. In some embodiments, the cell is a mammalian, primate, or human cell. In some embodiments, the cell is a human cell. In some embodiments, the cell is an immune effector cell (e.g., a population of immune effector cells), for example a T cell orNK cell. In embodiments, the T cell (e.g., population of T cells) is or comprises a CD4+ T cell, a CD8+ T cell, or a combination thereof. In some embodiments, the cell is a human T cell, e.g., a human T cell or a population of human T cells. In some embodiments, the cell is a population of human T cells that comprises cells that express CD4 and / or CD8. In embodiments, the cell or population of cells is autologous. In embodiments, the cell or population of cells is allogeneic.[000293] In another aspect, the present disclosure further provides cells, such as those described above, including a second gRNA molecule as described herein, e.g, a second gRNA molecule with a guide sequence different from that of the first gRNA molecule. In other embodiments, the two or more gRNA molecules are complementary to target sites within two different genes whose gene products associate to form a molecular complex. It will be understood that in any of the aspects and embodiments of the present disclosure in which two or more target sites of different genes (or different molecular complexes, e.g, when targeting TCR and HL A- A) are targeted, that for any or all of the different gene (or molecular complex) targets, two or more gRNAs may be employed with respect to one or more of said different genes or different molecular complexes. For example, in embodiments and aspects in which expression of TCR and expression of HLA-A is reduced or eliminated, the reduced or eliminated expression of TCR may be accomplished by, for example, one gRNA targeting TRAC, or by more than one gRNA molecule targeting TRAC; while at the same time, or alternatively, targeting of HLA-A may be accomplished by, for example, one gRNA molecule targeting HLA-A or by two or more gRNA molecules targeting HLA-A. In other embodiments, the two or more, e.g. two gRNA molecules are complementary to target sites within different genes. Such cells may comprise alterations, e.g., indels or base conversions, at or near each target site such that expression of the functional gene product of more than one gene is reduced or eliminated. As discussed above, in such embodiments, more than one gRNA molecule targeted to each of the different genes may be employed.[000294] In some embodiments, the cell comprises one or more gRNA molecules comprising a guide sequence complementary with a target sequence of HLA-A, HLA-B, TRAC, CIITA, and / or TGFBR2.[000295] In certain embodiments, the cell comprises one or more gRNA molecules comprising a guide sequence complementary with a target sequence of HLA-A, HLA-B, TRAC, and CIITA.[000296] In some embodiments, the present disclosure provides a cell, e.g., a cell comprising an anti-BCMA CAR, e.g., as described herein, that comprises one or more modifications (e.g., nucleotide insertions or deletions) to an endogenous gene encoding an HLA-A, HLA-B, TRAC, CIITA, and / or TGFBR2.[000297] In certain embodiments, the present disclosure provides a cell, e.g., a cell comprising an anti-BCMA CAR, e.g., as described herein, that comprises one or more modifications (e.g., nucleotide insertions or deletions) to an endogenous gene encoding an HLA-A, HLA-B, TRAC, and CIITA.[000298] In some embodiments of the present disclosure, the engineered cell further comprises reduced or eliminated surface expression of HLA-A relative to an unmodified cell, the engineered cell comprising a genetic modification in the HLA-A gene, wherein the genetic modification is within the genetic coordinates chr6: 29942540-29945459. In some embodiments, the engineered cell has reduced or eliminated surface expression of HLA-A relative to an unmodified cell, the engineered cell comprising a genetic modification in the HLA-A gene, wherein the genetic modification is within the genomic coordinates chosen from chr6:29942891-29942915; and chr6:29942609-29942633;. In some embodiments, the genetic modification in HLA-A is within the genetic coordinates chr6:29942864-29942884. In some embodiments, the engineered cell has reduced or eliminated surface expression of HLA-A relative to an unmodified cell, the engineered cell comprising a genetic modification in the HLA-A gene, wherein the gene modification comprises at least one nucleotide within the genomic coordinates targeted by an HLA-A guide RNA comprising a guide sequence of SEQ ID NO: 403. In some embodiments, the genetic modification in HLA-A comprises at least one nucleotide within the genomic coordinates targeted by an HLA-A guide RNA comprising a guide sequence of SEQ ID NO: 423. In some embodiments, the genetic modification in HLA-A comprises at least one nucleotide within the genomic coordinates targeted by an HLA-A guide RNA comprising a guide sequence of SEQ ID NO: 446. In some embodiments, the genetic modification in HLA-A comprises at least one nucleotide within the genomic coordinates targeted by an HLA-A guide RNA comprising a guidesequence of SEQ ID NO: 404. In some embodiments, the genetic modification in HLA-A comprises at least one nucleotide within the genomic coordinates targeted by an HLA-A guide RNA comprising a guide sequence of SEQ ID NO: 412 or 414. In some embodiments, the genetic modification comprises an indel, a C to T substitution, or an A to G substitution within the genomic coordinates. In some embodiments, the genetic modification comprises a C to T substitution within the genomic coordinates. In some embodiments, the cell is homozygous for HLA-C. In some embodiments, the cell is homozygous for HLA-B and HLA-C.[000299] In some embodiments, the engineered cell further has reduced or eliminated surface expression of HLA-B relative to an unmodified cell, the engineered cell comprising a genetic modification in the HLA-B gene, wherein the genetic modification comprises at least one nucleotide within the genetic coordinates chr6:31354480-31357174. In some embodiments, the engineered cell has reduced or eliminated surface expression of HLA-B relative to an unmodified cell, the engineered cell comprising a genetic modification in the HLA-B gene, wherein the genetic modification is within the genomic coordinates: chr6:31355222-31355246, chr6:31355221-31355245, or chr6:31355205-31355229. In some embodiments, the engineered cell has reduced or eliminated surface expression of HLA-B relative to an unmodified cell, the engineered cell comprising a genetic modification in the HLA-B gene, wherein the gene modification comprises at least one nucleotide within the genomic coordinates targeted by an HLA-B guide RNA comprising a guide sequence of SEQ ID NO: 405-407. In some embodiments, the engineered cell has reduced or eliminated surface expression of HLA-B relative to an unmodified cell, the engineered cell comprising a genetic modification in the HLA-B gene, wherein the gene modification comprises at least one nucleotide within the genomic coordinates targeted by an HLA-B guide RNA comprising a guide sequence of SEQ ID NO: 406. In other embodiments, the engineered cell has reduced or eliminated surface expression of HLA-B relative to an unmodified cell, the engineered cell comprising a genetic modification in the HLA-B gene, wherein the gene modification comprises at least one nucleotide within the genomic coordinates targeted by an HLA-B guide RNA comprising a guide sequence of SEQ ID NO: 426. In other embodiments, the engineered cell has reduced or eliminated surface expression of HLA-B relative to an unmodified cell, the engineered cell comprising a genetic modification in the HLA-B gene, wherein the gene modification comprises at least one nucleotide within the genomic coordinates targeted by an HLA-B guide RNA comprising a guide sequence of SEQ ID NO: 452. In some embodiments, the genetic modification comprises an indel, a C to Tsubstitution, or an A to G substitution within the genomic coordinates. In some embodiments, the genetic modification comprises a C to T substitution within the genomic coordinates. In some embodiments, the cell is homozygous for HLA-C.[000300] In some embodiments, the engineered cell further has reduced or eliminated surface expression of TRAC relative to an unmodified cell, the engineered cell comprising a genetic modification in the TRAC gene, wherein the genetic modification comprises at least one nucleotide within the genetic coordinates chrl4:22547462-22551621. In some embodiments, the engineered cell has reduced or eliminated surface expression of TRAC relative to an unmodified cell, the engineered cell comprising a genetic modification in the TRAC gene, wherein the genetic modification is within the genomic coordinates chr14:22547524-22547544. In some embodiments, the engineered cell has reduced or eliminated surface expression of TRAC relative to an unmodified cell, the engineered cell comprising a genetic modification in the TRAC gene, wherein the gene modification comprises at least one nucleotide within the genomic coordinates targeted by a TRAC guide RNA comprising a guide sequence of SEQ ID NO: 413. In some embodiments, the gene modification comprises at least one nucleotide within the genomic coordinates targeted by a TRAC guide RNA comprising a guide sequence of SEQ ID NO: 433 or 434. In some embodiments, the gene modification comprises at least one nucleotide within the genomic coordinates targeted by a TRAC guide RNA comprising a guide sequence of SEQ ID NO: 464. In some embodiments, the genetic modification comprises an indel, a C to T substitution, or an A to G substitution within the genomic coordinates. In some embodiments, the genetic modification comprises an indel within the genomic coordinates. In some embodiments, the cell is homozygous for HLA-C. In some embodiments, the cell is homozygous for HLA-B and HLA-C.[000301] In some embodiments, the engineered cell further has reduced or eliminated surface expression of MHC class II relative to an unmodified cell, the engineered cell comprising a genetic modification in the CIITA gene, wherein the genetic modification is within the genetic coordinates chosen from: (a) chrl6:10877363-10907788 and (b) chr16:10906515-10908136. In other embodiments, the genetic modification is within the genetic coordinates (a) chrl6: 10907504-10907528 or (b) chr16: 10906643-10906667. In some embodiments, the engineered cell has reduced or eliminated surface expression of CIITA relative to an unmodified cell, the engineered cell comprising a genetic modification in the CIITA gene, wherein the genetic modification is within the genomic coordinates chrl6: 10906853-10906873. In some embodiments, the engineered cell has reduced or eliminated surface expression of MHC class II relative to an unmodified cell, the engineered cell comprising agenetic modification in the CIITA gene, wherein the gene modification comprises at least one nucleotide within the genomic coordinates targeted by a CIITA guide RNA comprising a guide sequence of SEQ ID NO: 401 or SEQ ID NO: 402. In some embodiments, the engineered cell has reduced or eliminated surface expression of MHC class II relative to an unmodified cell, the engineered cell comprising a genetic modification in the CIITA gene, wherein the gene modification comprises at least one nucleotide within the genomic coordinates targeted by a CIITA guide RNA comprising a guide sequence of SEQ ID NO: 422. In some embodiments, the engineered cell has reduced or eliminated surface expression of MHC class II relative to an unmodified cell, the engineered cell comprising a genetic modification in the CIITA gene, wherein the gene modification comprises at least one nucleotide within the genomic coordinates targeted by a CIITA guide RNA comprising a guide sequence of SEQ ID NO: 443. In some embodiments, the engineered cell has reduced or eliminated surface expression of MHC class II relative to an unmodified cell, the engineered cell comprising a genetic modification in the CIITA gene, wherein the gene modification comprises at least one nucleotide within the genomic coordinates targeted by a CIITA guide RNA comprising a guide sequence of SEQ ID NO: 411 or SEQ ID NO: 415. In some embodiments, the genetic modification comprises an indel, a C to T substitution, or an A to G substitution within the genomic coordinates. In some embodiments, the genetic modification comprises a C to T substitution within the genomic coordinates. In some embodiments, the cell is homozygous for HLA-C. In some embodiments, the cell is homozygous for HLA-B and HLA-C.[000302] In some embodiments, the engineered cell has reduced or eliminated surface expression of HLA-A, TRAC, and MHC class II, relative to an unmodified cell, the engineered cell comprising a genetic modification in the HLA-A, TRAC, and CIITA gene. In some embodiments, the cell is homozygous for HLA-C. In some embodiments, the cell is homozygous for HLA-B and HLA-C.[000303] In some embodiments, the engineered cell has reduced or eliminated surface expression of HLA-A, HLA-B, TRAC, and MHC class II relative to an unmodified cell, the engineered cell comprising a genetic modification in the HLA-A, HLA-B, TRAC, and CIITA gene. In some embodiments, the cell is homozygous for HLA- C.[000304] In some embodiments, the engineered cell has reduced or eliminated surface expression of HLA-A, TRAC, MHC class II, and TGFBR2 relative to an unmodified cell, the engineered cell comprising a genetic modification in the HLA-A, TRAC, CIITA, andTGFBR2 genes. In some embodiments, the cell is homozygous for HLA-C. In some embodiments, the cell is homozygous for HLA-B and HLA-C.[000305] In some embodiments, the engineered cell has reduced or eliminated surface expression of HLA-A, HLA-B, TRAC, MHC class II, and TGFBR2 relative to an unmodified cell, the engineered cell comprising a genetic modification in the HLA-A, HLA-B, TRAC, CIITA, and TGFBR2 genes. In some embodiments, the cell is homozygous for HLA-C.[000306] In some embodiments, the present disclosure provides for an engineered cell comprising a modified HLA-A gene, a modified TRAC gene, and / or a modified CIITA gene, wherein the engineered cell expresses an anti-BCMA chimeric antigen receptor (CAR) or comprises a nucleic acid encoding an anti-BCMA CAR. In some embodiments, the cell is homozygous for HLA-C. In some embodiments, the cell is homozygous for HLA-B and HLA-C.[000307] In some embodiments, the genetic modification in HLA-A is within the genetic coordinates chr6: 29942540-29945459. In some embodiments, the genetic modification in HLA-A is within the genomic coordinates chosen from chr6:29942891-29942915; and chr6:29942609-29942633. In some embodiments, the genetic modification in HLA-A is within the genetic coordinates chr6:29942864-29942884. In some embodiments, the genetic modification in HLA-A comprises at least one nucleotide within the genomic coordinates targeted by an HLA-A guide RNA comprising a guide sequence of SEQ ID NO: 403. In some embodiments, the genetic modification in HLA-A comprises at least one nucleotide within the genomic coordinates targeted by an HLA-A guide RNA comprising a guide sequence of SEQ ID NO: 404. In some embodiments, the genetic modification in HLA-A comprises at least one nucleotide within the genomic coordinates targeted by an HLA-A guide RNA comprising a guide sequence of SEQ ID NO: 412 or 414. In some embodiments, the genetic modification comprises an indel, a C to T substitution, or an A to G substitution within the genomic coordinates. In some embodiments, the genetic modification comprises a C to T substitution within the genomic coordinates.[000308] In some embodiments, the genetic modification in TRAC comprises at least one nucleotide within the genetic coordinates chrl4:22547462-22551621. In some embodiments, the engineered cell has reduced or eliminated surface expression of TRAC relative to an unmodified cell, the engineered cell comprising a genetic modification in the TRAC gene, wherein the genetic modification is within the genomic coordinates chr14:22547524-22547544. In some embodiments, the genetic modification in TRAC comprises at least one nucleotide within the genomic coordinates targeted by a TRAC guide RNA comprising aguide sequence of SEQ ID NO: 413. In some embodiments, the genetic modification in TRAC comprises at least one nucleotide within the genomic coordinates targeted by a TRAC guide RNA comprising a guide sequence of SEQ ID NO: 433 or 434. In some embodiments, the genetic modification comprises an indel, a C to T substitution, or an A to G substitution within the genomic coordinates. In some embodiments, the genetic modification comprises a C to T substitution within the genomic coordinates.[000309] In some embodiments, the genetic modification in CIITA is within the genetic coordinates chosen from: (a) chrl6:10877363-10907788 and (b) chr16:10906515-10908136. In some embodiments, the engineered cell has reduced or eliminated surface expression of CIITA relative to an unmodified cell, the engineered cell comprising a genetic modification in the CIITA gene, wherein the genetic modification is within the genomic coordinates chosen from chr16: 10906643-10906667 and chrl6: 10907504-10907528. In some embodiments, the engineered cell has reduced or eliminated surface expression of CIITA relative to an unmodified cell, the engineered cell comprising a genetic modification in the CIITA gene, wherein the genetic modification is within the genomic coordinateschrl6: 10906853-10906873. In some embodiments, the genetic modification in CIITA comprises at least one nucleotide within the genomic coordinates targeted by a CIITA guide RNA comprising a guide sequence of SEQ ID NO: 402 or 401. In some embodiments, the genetic modification in CIITA comprises at least one nucleotide within the genomic coordinates targeted by a CIITA guide RNA comprising a guide sequence of SEQ ID NO: 411. In some embodiments, the genetic modification comprises an indel, a C to T substitution, or an A to G substitution within the genomic coordinates. In some embodiments, the genetic modification comprises a C to T substitution within the genomic coordinates.[000310] In some embodiments, the present disclosure provides for an engineered cell comprising a modified HLA-A gene, a modified HLA-B gene, a modified TRAC gene, and / or a modified CIITA gene, wherein the engineered cell expresses an anti-BCMA chimeric antigen receptor (CAR) or comprises a nucleic acid encoding an anti-BCMA CAR. In some embodiments, the cell is homozygous for HLA-C.[000311] In some embodiments, the genetic modification in HLA-A is within the genetic coordinates chr6: 29942540-29945459. In some embodiments, the genetic modification in HLA-A is within the genomic coordinates chosen from chr6:29942891-29942915; and chr6:29942609-29942633. In some embodiments, the genetic modification in HLA-A is within the genetic coordinates chr6:29942864-29942884. In some embodiments, the genetic modification in HLA-A comprises at least one nucleotide within the genomic coordinatestargeted by an HLA-A guide RNA comprising a guide sequence of SEQ ID NO: 403. In some embodiments, the genetic modification in HLA-A comprises at least one nucleotide within the genomic coordinates targeted by an HLA-A guide RNA comprising a guide sequence of SEQ ID NO: 404. In some embodiments, the genetic modification in HLA-A comprises at least one nucleotide within the genomic coordinates targeted by an HLA-A guide RNA comprising a guide sequence of SEQ ID NO: 412 or 414. In some embodiments, the genetic modification comprises an indel, a C to T substitution, or an A to G substitution within the genomic coordinates. In some embodiments, the genetic modification comprises a C to T substitution within the genomic coordinates.[000312] In some embodiments, the genetic modification in HLA-B comprises at least one nucleotide within the genetic coordinates chr6:31354480-31357174. In some embodiments, the genetic modification in HLA-B is within the genomic coordinates: chr6:31355222-31355246, chr6:31355221-31355245, or chr6:31355205-31355229. In some embodiments, the genetic modification in HLA-B comprises at least one nucleotide within the genomic coordinates targeted by an HLA-B guide RNA comprising a guide sequence of SEQ ID NO: 405-407. In some embodiments, the genetic modification in HLA-B comprises at least one nucleotide within the genomic coordinates targeted by an HLA-B guide RNA comprising a guide sequence of SEQ ID NO: 406. In other embodiments, the genetic modification in HLA-B comprises at least one nucleotide within the genomic coordinates targeted by an HLA-B guide RNA comprising a guide sequence of SEQ ID NO: 426. In some embodiments, the genetic modification comprises an indel, a C to T substitution, or an A to G substitution within the genomic coordinates. In some embodiments, the genetic modification comprises a C to T substitution within the genomic coordinates.[000313] In some embodiments, the genetic modification in TRAC comprises at least one nucleotide within the genetic coordinates chrl4:22547462-22551621. In some embodiments, the engineered cell has reduced or eliminated surface expression of TRAC relative to an unmodified cell, the engineered cell comprising a genetic modification in the TRAC gene, wherein the genetic modification is within the genomic coordinates chr14:22547524-22547544. In some embodiments, the genetic modification in TRAC comprises at least one nucleotide within the genomic coordinates targeted by a TRAC guide RNA comprising a guide sequence of SEQ ID NO: 413. In some embodiments, the genetic modification in TRAC comprises at least one nucleotide within the genomic coordinates targeted by a TRAC guide RNA comprising a guide sequence of SEQ ID NO: 433 or 434. In some embodiments, the genetic modification comprises an indel, a C to T substitution, or an A to G substitutionwithin the genomic coordinates. In some embodiments, the genetic modification comprises a C to T substitution within the genomic coordinates.[000314] In some embodiments, the genetic modification in CIITA is within the genetic coordinates chosen from: (a) chrl6:10877363-10907788 and (b) chr16:10906515-10908136. In some embodiments, the engineered cell has reduced or eliminated surface expression of CIITA relative to an unmodified cell, the engineered cell comprising a genetic modification in the CIITA gene, wherein the genetic modification is within the genomic coordinates chosen from chr16: 10906643-10906667 and chrl6: 10907504-10907528. In some embodiments, the genetic modification in the CIITA gene is within the genomic coordinates chrl6: 10906853-10906873. In some embodiments, the genetic modification in CIITA comprises at least one nucleotide within the genomic coordinates targeted by a CIITA guide RNA comprising a guide sequence of SEQ ID NO: 402. In some embodiments, the genetic modification in CIITA comprises at least one nucleotide within the genomic coordinates targeted by a CIITA guide RNA comprising a guide sequence of SEQ ID NO: 401. In some embodiments, the genetic modification in CIITA comprises at least one nucleotide within the genomic coordinates targeted by a CIITA guide RNA comprising a guide sequence of SEQ ID NO: 411. In some embodiments, the genetic modification comprises an indel, a C to T substitution, or an A to G substitution within the genomic coordinates. In some embodiments, the genetic modification comprises a C to T substitution within the genomic coordinates. In some embodiments, the engineered cell described herein further comprises a genetic modification in TGFBR2. For example, an engineered cell may comprise at least one nucleotide within the genomic coordinates: chr3:30606864-30691614. In some embodiments, the genetic modification in TGFBR2 is within the genomic coordinates: 30606891-30691605. In some embodiments, the genetic modification in TGFBR2 is within the genomic coordinates chr3:30674205-30674229. In some embodiments, the genetic modification in TGFBR2 comprises at least one nucleotide within the genomic coordinates targeted by a TGFBR2 guide RNA comprising a guide sequence of SEQ ID NO: 301. In some embodiments, the genetic modification in TGFBR2 is within the genomic coordinates: chr3:30606864-30691614. In some embodiments, the genetic modification in TGFBR2 comprises at least one nucleotide within the genomic coordinates targeted by a TGFBR2 guide RNA comprising a guide sequence of SEQ ID NO: 302. In some embodiments, the genetic modification comprises an indel, a C to T substitution, or an A to G substitution within the genomic coordinates. In some embodiments, the genetic modification comprises a C to T substitution within the genomic coordinates.[000315] In some embodiments, of the present disclosure, the genetic modification comprises at least 2, at least 3, at least 4, at least 5, at least 6, at least 7, at least 8, at least 9, or at least 10 contiguous nucleotides within the genomic coordinates, e.g., coordinates described herein for HLA-A, HLA-B, CIITA, and / or TRAC; and / or further TGFBR2. In some embodiments, the genetic modification comprises an indel. In some embodiments, the genetic modification comprises an insertion of a heterologous coding sequence. In some embodiments, the genetic modification comprises at least one A to G substitution within the genomic coordinates. In some embodiments, the genetic modification comprises at least one C to T substitution within the genomic coordinates.[000316] In some embodiments, the cell has reduced expression of TRAC protein on the surface of the cell. In some embodiments, the cell has a genetic modification in the CIITA gene. In some embodiments, the cell has reduced expression of MHC class II molecules on the surface of the cell.[000317] In some embodiments, the present disclosure provides for a population of cells, comprising the engineered cells of the present disclosure.[000318] In some embodiments, the present disclosure provides a pharmaceutical composition comprising the engineered cell of the disclosure.[000319] In some aspects, the present disclosure provides for an engineered cell, population of cells, pharmaceutical composition, or method, wherein the engineered cell is an immune cell.[000320] In some aspects, the present disclosure provides for an engineered cell, population of cells, pharmaceutical composition, or method, wherein the engineered cell is a stem cell.[000321] In some aspects, the present disclosure provides for an engineered cell, population of cells, pharmaceutical composition, or method, wherein the engineered cell is a primary cell.[000322] In some aspects, the present disclosure provides for an engineered cell, population of cells, pharmaceutical composition, or method, wherein the engineered cell is engineered with a genomic editing system. In some embodiments, the genomic editing system comprises an RNA-guided DNA-binding agent or a nucleic acid encoding an RNA-guided DNA-binding agent. In some embodiments, wherein the RNA-guided DNA-binding agent or the RNA-guided DNA-binding agent encoded by the nucleic acid is S. pyogenes Cas9 (SpyCas9). In some embodiments, wherein the RNA-guided DNA-binding agent or the RNA-guided DNA-binding agent encoded by the nucleic acid is N. meningitidis Cas9 (NmeCas9). In some embodiments, the RNA-guided DNA-binding agent or the RNA-guided DNA-binding agentencoded by the nucleic acid has double-stranded endonuclease activity. The RNA-guided DNA-binding agent or the RNA-guided DNA-binding agent encoded by the nucleic acid has nickase activity. In some embodiments, the RNA-guided DNA-binding agent or the RNA-guided DNA-binding agent encoded by the nucleic acid comprises a dCas9 DNA-binding domain. In some embodiments, the RNA-guided DNA-binding agent or nucleic acid encoding the RNA-guided DNA-binding agent is a A to G base editor. In some embodiments, the RNA-guided DNA-binding agent or nucleic acid encoding the RNA-guided DNA-binding agent is a C to T base editor.[000323] In some embodiments, the guide RNA is provided to the cell in a vector. In some embodiments, the RNA-guided DNA-binding agent is provided to the cell in a vector, optionally in the same vector as the guide RNA. In some embodiments, the exogenous nucleic acid is provided to the cell in a vector. In some embodiments, the vector is a viral vector. In some embodiments, the vector is a non-viral vector.[000324] In some embodiments, the guide RNA is provided to the cell in a lipid nanoparticle (LNP), optionally in the same LNP an RNA-guided DNA-binding agent is provided. In some embodiments, the exogenous nucleic acid is provided to the cell in a lipid nanoparticle (LNP). In some embodiments, the guide RNA is a single guide RNA. In some embodiments, the guide RNA comprises a 5’ end modification or a 3’ end modification.[000325] In embodiments, said modifications reduce or eliminate expression of said gene. In embodiments, the present disclosure provides a cell, e.g., a cell comprising a CAR, e.g., as described herein, that is HLA-A- (e.g., has a level of expression of HLA-A greater than 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% lower than that of an unmodified cell of the same type, as detected by FACS, e.g., FACS using an anti-HLA-A antibody), HLA-B-(e.g., has a level of expression of HLA-B greater than 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% lower than that of an unmodified cell of the same type, as detected by FACS, e.g., FACS using an anti -HLA-B antibody), TCR- (e.g., has a level of expression of TCR greater than 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% lower than that of an unmodified cell of the same type, as detected by FACS, e.g, FACS using an anti-CD3 antibody), CIITA- (e.g, has a level of expression of CIITA and / or a MHC class II protein greater than 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% lower than that of an unmodified cell of the same type, as detected by FACS, e.g, FACS using an anti-CIITA antibody), or TGFBR2- (e.g, has a level of expression of TGFBR2 protein greater than 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% lower than that of anunmodified cell of the same type, as detected by FACS, e.g., FACS using an anti-TGFBR2 antibody).[000326] In some embodiments of the present disclosure, a cell or population of cells of the disclosure comprises: (a) a nucleic acid sequence encoding an anti-BCMA CAR, e.g., as disclosed herein; (b) an indel at or near a sequence of a gene encoding one or more of HLA-A, HLA-B, TRAC, and CIITA, or its regulatory elements, e.g., an indel at or near a target sequence of a gRNA comprising a guide sequence to one or more of HLA-A, HLA-B, TRAC, TGFBR2, and CIITA, e.g., comprising a guide sequence listed in Tables 2 or 3.[000327] In any of the embodiments and aspects, the cell may further comprise one or more CRISPR systems, e.g., as described herein, comprising the gRNA molecule(s) indicated. In some embodiments, the cell comprises one or more ribonuclear protein (RNP) complexes each comprising a Cas9 molecule, e.g., as described herein, and a gRNA molecule comprising the indicated guide sequence, e.g., as described herein. In some embodiments, including in any of the methods described herein, where gRNAs to more than one target sequence are employed, the gRNAs (and CRISPR systems comprising said gRNAs) may be introduced into the cell simultaneously. In other embodiments, including in any of the methods described herein, where gRNAs to more than one target sequence are employed, the gRNAs (and CRISPR systems comprising said gRNAs) may be introduced into the cell sequentially.[000328] In an aspect involving any of the aforementioned embodiments or aspects, the population of cells comprises at least 20%, e.g., at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, or at least 99%, of cells which include an indel at or near each of the target sequences targeted by each of the gRNA molecules. Said population may be obtained, for example, by utilizing high efficiency gRNA molecules (e.g., gRNA molecules which cause an indel in >85% of said cells which are exposed to said gRNA molecule), or by enriching the population for the desired cell, e.g., by selecting for the desired cell population, e.g., by affinity chromatography or cell sorting.Exemplary Engineered Cell Compositions[000329] In addition to providing for the engineered cells or cell populations as described in the above subsection, the present disclosure also provides for engineered cells, cell populations, pharmaceutical compositions, and uses thereof as follows.[000330] In some embodiments, provided herein is an engineered human T cell comprising multiple genetic modifications and an anti-BCMA chimeric antigen receptor (CAR), wherein(a) the engineered human T cell comprises a genetic modification in the HLA-A gene and reduced or eliminated surface expression of HLA-A relative to an unmodified cell, a genetic modification in the HLA-B gene and reduced or eliminated surface expression of HLA-B relative to an unmodified cell, a genetic modification in the CIITA gene and reduced or eliminated surface expression of MHC class II relative to an unmodified cell, and (b) the anti-BCMA CAR comprises an antigen-binding domain that specifically binds to BCMA, wherein the antigen-binding domain comprises a monospecific, bivalent VHH comprising a first heavy chain variable (VH) region and a second VH region each comprising a complementarity determining region 1 (VH CDR1), a VH CDR2, and VH CDR3 as set forth in the amino acid sequences of SEQ ID NO: 63, SEQ ID NO: 65, and SEQ ID NO: 67, respectively, wherein the anti-BCMA CAR is inserted into the TRAC locus.[000331] In some embodiments, provided herein is an engineered human T cell comprising multiple genetic modifications and an anti-BCMA chimeric antigen receptor (CAR), wherein (a) the engineered human T cell comprises a genetic modification in the HLA-A gene within the genomic coordinates chr6:29942891-29942915, a genetic modification in the HLA-B gene within the genomic coordinates chr6:31355222-31355246, a genetic modification in the CIITA gene within the genomic coordinates chr16: 10906643-10906667, and a genetic modification in the TGFBR2 gene within the genomic coordinates chr3:30674205-30674229,, and (b) the anti-BCMA CAR comprises an antigen-binding domain that specifically binds to BCMA, wherein the antigen-binding domain comprises a monospecific, bivalent VHH comprising a first heavy chain variable (VH) region and a second VH region each comprising a complementarity determining region 1 (VH CDR1), a VH CDR2, and VH CDR3 as set forth in the amino acid sequences of SEQ ID NO: 63, SEQ ID NO: 65, and SEQ ID NO: 67, respectively, wherein the anti-BCMA CAR is inserted into the TRAC locus.[000332] In some embodiments, provided herein is an engineered human T cell comprising multiple genetic modifications and an anti-BCMA chimeric antigen receptor (CAR), wherein (a) the engineered human T cell comprises a genetic modification in the HLA-A gene within the genomic coordinates chr6:29942891-29942915, a genetic modification in the HLA-B gene within the genomic coordinates chr6:31355222-31355246, a genetic modification in the CIITA gene within the genomic coordinates chr16: 10906643-10906667, and a genetic modification in the TGFBR2 gene within the genomic coordinates chr3:30674205-30674229,, and (b) the anti-BCMA CAR comprises an antigen-binding domain that binds to BCMA, wherein the an antigen-binding domain that specifically binds to BCMA, wherein the antigen-binding domain comprises a monospecific, bivalent VHH comprising a first heavychain variable (VH) region and a second VH region each comprising a complementarity determining region 1 (VH CDR1), a VH CDR2, and VH CDR3 as set forth in the amino acid sequences of SEQ ID NO: 63, SEQ ID NO: 65, and SEQ ID NO: 67, respectively, wherein the anti-BCMA CAR is inserted into the TRAC locus within the genomic coordinates chr14:22547524-22547544.[000333] In some embodiments, provided herein is a pharmaceutical composition comprising a population of T cells, wherein the population of T cells comprises CD4+ T cells and / or CD8+ T cells, which comprise an engineered human T cell comprising multiple genetic modifications and an anti-BCMA chimeric antigen receptor (CAR), wherein (a) the engineered human T cell comprises a genetic modification in the HLA-A gene and reduced or eliminated surface expression of HLA-A relative to an unmodified cell, a genetic modification in the HLA-B gene and reduced or eliminated surface expression of HLA-B relative to an unmodified cell, and a genetic modification in the CIITA gene and reduced or eliminated surface expression of MHC class II relative to an unmodified cell, and (b) the anti-BCMA CAR comprises an antigen-binding domain that binds to BCMA, wherein the an antigen-binding domain that specifically binds to BCMA, wherein the antigen-binding domain comprises a monospecific, bivalent VHH comprising a first heavy chain variable (VH) region and a second VH region each comprising a complementarity determining region 1 (VH CDR1), a VH CDR2, and VH CDR3 as set forth in the amino acid sequences of SEQ ID NO: 63, SEQ ID NO: 65, and SEQ ID NO: 67, respectively, wherein the anti-BCMA CAR is inserted into the TRAC locus. In certain embodiments, the engineered human T cell further contains a genetic modification in the TGFBR2 gene and reduced or eliminated surface expression of TGFBR2 relative to an unmodified cell.[000334] In some embodiments, provided herein is a population of T cells, wherein the population of T cells comprises CD4+ T cells and / or CD8+ T cells, which comprise an engineered human T cell comprising multiple genetic modifications and an anti-BCMA chimeric antigen receptor (CAR), wherein (a) the engineered human T cell comprises a genetic modification in the HLA-A gene within the genomic coordinates chr6:29942891-29942915, a genetic modification in the HLA-B gene within the genomic coordinates chr6:31355222-31355246, a genetic modification in the CIITA gene within the genomic coordinates chr16: 10906643-10906667,, and (b) the anti-BCMA CAR comprises an antigenbinding domain that specifically binds to BCMA, wherein the antigen-binding domain comprises a monospecific, bivalent VHH comprising a first heavy chain variable (VH) region and a second VH region each comprising a complementarity determining region 1 (VHCDR1), a VH CDR2, and VH CDR3 as set forth in the amino acid sequences of SEQ ID NO: 63, SEQ ID NO: 65, and SEQ ID NO: 67, respectively, wherein the anti-BCMA CAR is inserted into the TRAC locus. In certain embodiments, the engineered human T cell further comprises a genetic modification in the TGFBR2 gene within the genomic coordinates chr3:30674205-30674229.[000335] In some embodiments, provided herein is a population of T cells, wherein the population of T cells comprises CD4+ T cells and / or CD8+ T cells, which comprise an engineered human T cell comprising multiple genetic modifications and an anti-BCMA chimeric antigen receptor (CAR), wherein (a) the engineered human T cell comprises a genetic modification in the HLA-A gene within the genomic coordinates chr6:29942891-29942915, a genetic modification in the HLA-B gene within the genomic coordinates chr6:31355222-31355246, a genetic modification in the CIITA gene within the genomic coordinates chr16: 10906643-10906667, a genetic modification in the TGFBR2 gene within the genomic coordinates chr3:30674205-30674229,, and (b) the anti-BCMA CAR comprises an antigen-binding domain that binds to BCMA, wherein the an antigen-binding domain that specifically binds to BCMA, wherein the antigen-binding domain comprises a monospecific, bivalent VHH comprising a first heavy chain variable (VH) region and a second VH region each comprising a complementarity determining region 1 (VH CDR1), a VH CDR2, and VH CDR3 as set forth in the amino acid sequences of SEQ ID NO: 63, SEQ ID NO: 65, and SEQ ID NO: 67, respectively, wherein the anti-BCMA CAR is inserted into the TRAC locus within the genomic coordinates chr14:22547524-22547544. Non-limiting methods and compositions used for engineering a population of T cells is described in Example 13.[000336] In some embodiments, provided herein is a population of T cells, wherein the population of T cells comprises CD4+ T cells and / or CD8+ T cells, which comprise an engineered human T cell comprising multiple genetic modifications and an anti-BCMA chimeric antigen receptor (CAR), wherein (a) the engineered human T cell comprises a genetic modification in the HLA-A gene within the genomic coordinates chr6:29942864-29942884, a genetic modification in the CIITA gene within the genomic coordinates chrl6: 10906853-10906873, and (b) the anti-BCMA CAR comprises an antigen-binding domain that binds to BCMA, wherein the an antigen-binding domain that specifically binds to BCMA, wherein the antigen-binding domain comprises a monospecific, bivalent VHH comprising a first heavy chain variable (VH) region and a second VH region each comprising a complementarity determining region 1 (VH CDR1), a VH CDR2, and VH CDR3 as set forth in the amino acid sequences of SEQ ID NO: 63, SEQ ID NO: 65, and SEQ ID NO: 67,respectively, wherein the anti-BCMA CAR is inserted into the TRAC locus within the genomic coordinates chr14:22547524-22547544. Non-limiting methods and compositions used for engineering a population of T cells is described in Example 10.[000337] In some embodiments, in the engineered human T cell, the VH region comprises the amino acid sequence of SEQ ID NO: 81. In some embodiments, in the engineered human T cell, the anti-BCMA CAR comprises the amino acid sequence of SEQ ID NO: 83.[000338] In some embodiments, the engineered human T cell is a CD4+ or CD8+ T cell. In some embodiments, the engineered human T cell is a CD4+ T cell. In some embodiments, the engineered human T cell is a CD8+ T cell.[000339] In some embodiments, the engineered human T cell is homozygous for HLA-C. In some embodiments, the engineered human T cell is homozygous for HLA-B and for HLA-C.[000340] In some embodiments, provided herein is a method of administering the above engineered human T cell or pharmaceutical composition to a subject in need thereof. In some embodiments, provided herein is a method of administering the above engineered human T cell or pharmaceutical composition to a subject as an adoptive cell transfer (ACT) therapy.[000341] In some embodiments, provided herein is a method of treating a disease or disorder, comprising administering the above engineered human T cell or pharmaceutical composition to a subject in need thereof.[000342] In some embodiments, provided herein is the above engineered human T cell or pharmaceutical composition, for use in administration to a subject as an adoptive cell transfer (ACT) therapy. In some embodiments, provided herein is the above engineered human T cell or pharmaceutical composition, for use in treating a subject having a cancer. In some embodiments, provided herein is the above engineered human T cell or pharmaceutical composition, for use in treating a subject having an infectious disease. In some embodiments, provided herein is the above engineered human T cell or pharmaceutical composition, for use in treating a subject having an autoimmune disease.[000343] In some embodiments, the disease or disorder is a cancer. In some embodiments, the cancer is a solid tumor or a hematological malignancy. In some embodiments, the solid tumor is renal cell carcinoma. In some embodiments, the hematological malignancy is acute myeloid leukemia. In some embodiments, the hematological malignancy is multiple myeloma.Methods and Compositions for Generating Cells Comprising Anti-BCMA Chimeric Antigen Receptors (CARs) and Reduced or Eliminated Surface Expression of One or More of HLA-A, HLA-B, TRAC, MHC Class II, and TGFBR2[000344] In some embodiments, a method of making an engineered cell is provided, the method comprising contacting a cell with (a) a nucleic acid or mRNA encoding an anti-BCMA CAR, or an expression vector encoding a nucleic acid or mRNA encoding an anti-BCMA CAR; and (b) at least one genomic editing tool comprising a genomic editor and at least one guide RNA, wherein the at least one guide RNA targets a genomic locus chosen from the HLA-A, HLA-B, TRAC, CIITA, and optionally TGFBR2 locus.[000345] In some embodiments, a method of making an engineered cell is provided, the method comprising (a) providing an engineered cell which has reduced or eliminated surface expression of one or more of HLA-A, HLA-B, MHC class II, TRAC, and optionally TGFBR2, relative to an unmodified cell; and (b) contacting the cell with the nucleic acid or mRNA encoding an anti-BCMA CAR, or an expression vector encoding a nucleic acid or mRNA encoding an anti-BCMA CAR.[000346] In some embodiments, a method of making an engineered cell is provided, the method comprising (a) providing an engineered cell which has reduced or eliminated surface expression of one or more of HLA-A, HLA-B, MHC class II, TRAC, and TGFBR2, relative to an unmodified cell; and (b) contacting the cell with the nucleic acid or mRNA encoding an anti-BCMA CAR, or an expression vector encoding a nucleic acid or mRNA encoding an anti-BCMA CAR.1. Anti-BCMA CAR Knock-In[000347] The present disclosure provides methods and compositions for generating cells comprising an anti-BCMA CAR encoded by an exogenous nucleic acid. In some embodiments, the anti-BCMA CAR is an anti-BCMA CAR disclosed herein.[000348] In some embodiments, the methods comprise contacting a cell with an exogenous nucleic acid encoding an anti-BCMA CAR. In some embodiments, the anti-BCMA CAR is an anti-BCMA CAR disclosed herein.[000349] In some embodiments, an exogenous nucleic acid encoding an anti-BCMA CAR is inserted into the genome of the target cell. In some embodiments, the exogenous nucleic acid is integrated into the genome of the target cell. In some embodiments, the exogenous nucleic acid is integrated into the genome of the target cell by homologous recombination (HR). Insome embodiments, the exogenous nucleic acid is integrated into the genome of the target cell by blunt end insertion. In some embodiments, the exogenous nucleic acid is integrated into the genome of the target cell by non-homologous end joining. In some embodiments, the exogenous nucleic acid is integrated into a safe harbor locus in the genome of the cell. In some embodiments, the exogenous nucleic acid is integrated into one of the TRAC locus or CIITA locus. In some embodiments, the lipid nucleic acid assembly composition is a lipid nanoparticle (LNP).[000350] In some embodiments, the methods produce a composition comprising an engineered cell comprising an exogenous nucleic acid encoding an anti-BCMA CAR.[000351] In some embodiments, an allogeneic cell is provided wherein the cell comprises an exogenous nucleic acid encoding an anti-BCMA CAR.[000352] The term “exogenous nucleic acid,” “template nucleic acid,” or “donor template,” as used herein, refers to a nucleic acid to be inserted at or near a target sequence that has been modified, e.g., cleaved, by a CRISPR system of the present disclosure. In an embodiment, an endogenous nucleic acid sequence at or near the target site is modified to have some or all of the sequence of the exogenous nucleic acid, typically at or near cleavage site(s). In an embodiment, the exogenous nucleic acid is single stranded. In an alternate embodiment, the exogenous nucleic acid is double stranded. In an embodiment, the template nucleic acid is DNA, e.g., double stranded DNA. In an alternate embodiment, the template nucleic acid is single stranded DNA.[000353] In certain embodiments, the exogenous nucleic acid comprises sequence encoding an anti-BCMA CAR, e.g., an anti-BCMA CAR as described herein.[000354] In an embodiment, the template nucleic acid alters the structure of the target position by participating in a homology directed repair event. In an embodiment, the template nucleic acid alters the sequence of the target position. In an embodiment, the template nucleic acid results in the incorporation of a modified, or non-naturally occurring base into the target nucleic acid.[000355] In an embodiment, a single nick can be used to induce HDR. It is contemplated herein that a single nick can be used to increase the ratio of HDR, HR or NHEJ at a given cleavage site.[000356] The double strand break or single strand break in one of the strands should be sufficiently close to target position such that correction occurs. In an embodiment, the distance is not more than 50, 100, 200, 300, 350 or 400 nucleotides. While not wishing to be bound by theory, it is believed that the break should be sufficiently close to target position such that thebreak is within the region that is subject to exonuclease-mediated removal during end resection. If the distance between the target position and a break is too great, the mutation may not be included in the end resection and, therefore, may not be corrected, as donor sequence may only be used to correct sequence within the end resection region.[000357] The homology arm should extend at least as far as the region in which end resection may occur, e.g., in order to allow the resected single stranded overhang to find a complementary region within the donor template. The overall length could be limited by parameters such as plasmid size or viral packaging limits. In an embodiment, a homology arm does not extend into repeated elements, e.g., ALU repeats, LINE repeats. A template may have two homology arms of the same or different lengths.[000358] Exemplary homology arm lengths include at least 25, 50, 100, 250, 500, 750 or 1000 nucleotides.[000359] Target position, as used herein, refers to a site on a target nucleic acid (e.g., the chromosome) that is modified by a Cas9 molecule-dependent process. For example, the target position can be a modified Cas9 molecule cleavage of the target nucleic acid and template nucleic acid directed modification, e.g., correction, of the target position. In an embodiment, a target position can be a site between two nucleotides, e.g., adjacent nucleotides, on the target nucleic acid into which one or more nucleotides is added. The target position may comprise one or more nucleotides that are altered, e.g., corrected, by a template nucleic acid. In an embodiment, the target position is within a target sequence (e.g., the sequence to which the gRNA binds). In an embodiment, a target position is upstream or downstream of a target sequence (e.g., the sequence to which the gRNA binds).[000360] Typically, the template sequence undergoes a breakage mediated or catalyzed recombination with the target sequence. In an embodiment, the template nucleic acid includes a sequence that corresponds to a site on the target sequence that is cleaved by a Cas9 mediated cleavage event. In an embodiment, the template nucleic acid includes sequence that corresponds to both, a first site on the target sequence that is cleaved in a first Cas9 mediated event, and a second site on the target sequence that is cleaved in a second Cas9 mediated event.[000361] A template nucleic acid comprises the following components: [5’ homology arm]-[insertion sequence]-[3’ homology arm]. The homology arms provide for recombination into the chromosome, which can replace the undesired element, e.g., a mutation or signature, with the replacement sequence. In an embodiment, the homology arms flank the most distal cleavage sites.[000362] In an embodiment, the 3’ end of the 5’ homology arm is the position next to the 5’ end of the replacement sequence. In an embodiment, the 5’ homology arm can extend at least 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 120, 150, 180, 200, 300, 400, 500, 600, 700, 800, 900, 1000, 1500, or 2000 nucleotides 5’ from the 5’ end of the replacement sequence.[000363] In an embodiment, the 5’ end of the 3’ homology arm is the position next to the 3’ end of the replacement sequence. In an embodiment, the 3’ homology arm can extend at least 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 120, 150, 180, 200, 300, 400, 500, 600, 700, 800, 900, 1000, 1500, or 2000 nucleotides 3’ from the 3’ end of the replacement sequence.[000364] It is contemplated herein that one or both homology arms may be shortened to avoid including certain sequence repeat elements, e.g., Alu repeats, LINE elements. For example, a 5’ homology arm may be shortened to avoid a sequence repeat element. In other embodiments, a 3’ homology arm may be shortened to avoid a sequence repeat element. In some embodiments, both the 5’ and the 3’ homology arms may be shortened to avoid including certain sequence repeat elements.[000365] It is contemplated herein that template nucleic acids for correcting a mutation may designed for use as a single-stranded oligonucleotide (ssODN). When using a ssODN, 5’ and 3’ homology arms may range up to about 200 base pairs (bp) in length, e.g., at least 25, 50, 75, 100, 125, 150, 175, or 200 bp in length. Longer homology arms are also contemplated for ssODNs as improvements in oligonucleotide synthesis continue to be made.[000366] In one aspect, the insertion sequence comprises nucleic acid sequence that encodes an anti-BCMA chimeric antigen receptor, e.g. as described herein. In one embodiment the insertion sequence further comprises a promotor operably linked to the nucleic acid sequence encoding a chimeric antigen receptor, e.g, an EF-1 alpha promoter. In one aspect, the insertion sequence comprises a vector encoding a chimeric antigen receptor, e.g, as described herein, or a portion thereof.2. HLA-A, HLA-B, TRAC, MHC Class II, and TGFBR2 Knock Out[000367] In some embodiments, the anti-BCMA CAR may be transduced into a cell. In some embodiments, the methods comprise contacting a cell with a donor nucleic acid encoding the anti-BCMA CAR for insertion into the genome of the cell.[000368] In some embodiments, multiplex gene editing may further be performed on a cell comprising an anti-BCMA CAR. In some embodiments, the methods comprise reducing or eliminating surface expression of one or more of HLA-A, HLA-B, TRAC, or MHC class II proteins comprising genetically modifying one or more of the HLA-A, HLA-B, TRAC, orCIITA genes comprising contacting the cell with a composition comprising one or more HLA-A, HLA-B, TRAC, or CIITA guide RNAs disclosed herein; and optionally an RNA-guided DNA binding agent or a nucleic acid encoding an RNA-guided DNA binding agent.[000369] In some embodiments, the methods comprise reducing or eliminating surface expression of TGFBR2 proteins comprising genetically modifying the TGFBR2 genes comprising contacting the cell with a composition comprising TGFBR2 guide RNAs disclosed herein; and optionally an RNA-guided DNA binding agent or a nucleic acid encoding an...

Claims

CLAIMSWhat is claimed is:

1. An anti-B cell maturation antigen (BCMA) chimeric antigen receptor (CAR) comprising:a. an antigen-binding domain that specifically binds to BCMA, wherein the antigen-binding domain comprises a monospecific, bivalent VHH comprising a first heavy chain variable (VH) region and a second VH region each comprising a complementarity determining region 1 (VH CDR1), a VH CDR2, and VH CDR3 as set forth in the amino acid sequences of SEQ ID NO: 63, SEQ ID NO: 65, and SEQ ID NO: 67, respectively,b. a transmembrane domain; andc. an intracellular domain (ICD) comprising a costimulatory domain comprising an amino acid sequence of SEQ ID NO: 71.

2. The anti -BCMA CAR of claim 1, wherein the first and / or the second VH region each comprise an amino acid sequence having at least 90%, 93%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO: 81, or wherein the first and / or the second VH region each comprises the amino acid sequence of SEQ ID NO: 81.

3. The anti -BCMA CAR of claim 1 or 2, wherein the first VH region comprises the amino acid sequence of SEQ ID NO: 81, and the second VH region comprises the amino acid sequence of SEQ ID NO: 81.

4. The anti -BCMA CAR of any one of claims 1-3 wherein the bivalent VHH comprises a linker between the first and second VH regions.

5. The anti -BCMA CAR of claim 4, wherein the linker is a glycine-serine linker.

6. The anti-BCMA CAR or claim 5, wherein the glycine-serine linker comprises the sequence of SEQ ID NO: 73.

7. The anti-BCMA CAR of any one of claims 1-6, wherein the antigen-binding domain comprises the amino acid sequence of SEQ ID NO: 84.WBD (US) 4901-8816-4240vl 3558. The anti-BCMA CAR of any one of claims 1-7, wherein the transmembrane domain comprises a CD8a transmembrane domain comprising an amino acid sequence of SEQ ID NO: 70.

9. The anti-BCMA CAR of claim 8, further comprising a hinge domain between the antigen-binding domain and the transmembrane domain, optionally wherein the hinge domain is a CD8a hinge domain, or fragment thereof, comprising an amino acid sequence of SEQ ID NO: 69.

10. The anti-BCMA CAR of any one of claims 1-9, wherein the intracellular domain further comprises an activation domain, optionally wherein the activation domain is a CD3z activation domain comprising an amino acid sequence of SEQ ID NO: 72.

11. The anti-BCMA CAR of any one of claims 1-10, comprising an amino acid sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 83.

12. An anti-BCMA CAR comprising the amino acid sequence of SEQ ID NO: 83.

13. The anti-BCMA CAR of any one of claims 1-12, wherein the first VH region is encoded by a nucleic acid sequence having at least 90%, 93%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO: 80 and the second VH region is encoded by a nucleic acid sequence having at least 90%, 93%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO: 80.

14. The anti-BCMA CAR of any one of claims 1-12, which is encoded by a nucleic acid sequence that is at least 95% identical to the nucleic acid sequence of SEQ ID NO: 82.

15. A nucleic acid encoding the anti-BCMA CAR of any one of claims 1-12.

16. The nucleic acid of claim 15, wherein the nucleic acid is an mRNA.WBD (US) 4901-8816-4240vl 35617. A nucleic acid encoding an anti-BCMA CAR, wherein the nucleic acid comprises a nucleic acid sequence of SEQ ID NO: 82, or a nucleic acid sequence that has at least 90%, 93%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO: 82.

18. An mRNA or protein encoded by the nucleic acid of any one of claims 15-17.

19. An expression vector operably linked to or comprising the nucleic acid of claim 15 or 17.

20. An engineered cell comprising the nucleic acid of claim 15 or 17, the mRNA of claim 16 or 18, or the expression vector of claim 19.

21. An engineered cell comprising the anti-BCMA CAR of any one of claims 1-14, optionally wherein the cell is transduced with an expression vector operably linked to or comprising a nucleic acid encoding the anti-BCMA CAR, and optionally wherein the expression vector directs expression of the anti-BCMA CAR in the cell.

22. The expression vector of claim 19, or the engineered cell of claim 20 or 21, wherein the expression vector comprises a retroviral or lentiviral expression vector.

23. The expression vector of claim 22, or the engineered cell of claim 21, wherein the expression vector comprises an AAV vector.

24. An engineered cell comprising an anti-BCMA chimeric antigen receptor (CAR), wherein the anti-BCMA CAR comprises:a. an antigen-binding domain that specifically binds to BCMA, wherein the antigen-binding domain comprises a monospecific, bivalent VHH comprising a first heavy chain variable (VH) region and a second VH region each comprising a complementarity determining region 1 (VH CDR1), a VH CDR2, and VH CDR3 as set forth in the amino acid sequences of SEQ ID NO: 63, SEQ ID NO: 65, and SEQ ID NO: 67, respectively,b. a transmembrane domain; andWBD (US) 4901-8816-4240vl 357c. an intracellular domain comprising a costimulatory domain comprising an amino acid sequence of SEQ ID NO: 71.

25. The engineered cell of claim 24, wherein the first and / or the second VH region each comprise an amino acid sequence having at least 90%, 93%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO: 81, or wherein the first and / or the second VH region comprise the amino acid sequence of SEQ ID NO: 81.

26. The engineered cell of claim 25, wherein the first VH region comprises the amino acid sequence of SEQ ID NO: 81, and the second VH region comprises the amino acid sequence of SEQ ID NO: 81.

27. The engineered cell of any one of claims 24-26, wherein the bivalent VHH comprises a linker between the first and second VH regions.

28. The engineered cell of claim 27, wherein the linker is a glycine-serine linker.

29. The engineered cell of claim 28, wherein the glycine-serine linker comprises the sequence of SEQ ID NO: 7330. The engineered cell of any one of claims 24-29, wherein the antigen-binding domain comprises the amino acid sequence of SEQ ID NO: 84.

31. The engineered cell of any one of claims 24-30, wherein the transmembrane domain comprises a CD8a transmembrane (TM) domain comprising an amino acid sequence of SEQ ID NO: 70.

32. The engineered cell of claim 31, further comprising a hinge domain between the antigen-binding domain and the transmembrane domain, optionally wherein the hinge domain is a CD8a hinge domain, or fragment thereof, comprising an amino acid sequence of SEQ ID NO: 69.WBD (US) 4901-8816-4240vl 35833. The engineered cell of any one of claims 24-32, wherein the intracellular domain further comprises an activation domain, optionally wherein the activation domain is a CD3z activation domain comprising an amino acid sequence of SEQ ID NO: 72.

34. The engineered cell of any one of claims 24-33, wherein the anti-BCMA CAR comprises an amino acid sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 83, or wherein the anti-BCMA CAR comprises the amino acid sequence of SEQ ID NO: 83.

35. A population of cells, wherein the population of cells comprises the engineered cell of any one of claims 24-34.

36. The engineered cell or population of cells of any one of claims 24-35, further comprising reduced or eliminated surface expression of HLA-A relative to an unmodified cell.

37. The engineered cell or population of cells of any one of claims 24-36, further comprising a genetic modification in the HLA-A gene, optionally wherein the genetic modification comprises at least one nucleotide within the genomic coordinates: (a) chr6:29942854-29942913 and chr6:29943518-29943619; and (b) chr6:29942540- 29945459.

38. The engineered cell or population of cells of claim 37, wherein the genetic modification is within the genomic coordinates chosen from chr6:29942891- 29942915; and chr6:29942609-29942633, and optionally wherein the genetic modification comprises at least one nucleotide within the genomic coordinates targeted by an HLA-A guide RNA comprising a guide sequence of SEQ ID NO: 403.

39. The engineered cell or population of cells of any one of claims 24-38, which has reduced or eliminated surface expression of HLA-B relative to an unmodified cell.

40. The engineered cell or population of cells of any one of claims 24-39, further comprising a genetic modification in the HLA-B gene, optionally wherein the genetic modification is within the genomic coordinates chosen from (a) chr6:31354480-WBD (US) 4901-8816-4240vl 35931357174 and (b) chr6:31357084-31354647.

41. The engineered cell of claim 40, wherein the genetic modification is within the genomic coordinates chosen from chr6:31355222-31355246, chr6:31355221- 31355245, and chr6:31355205-31355229, optionally wherein the genetic modification comprises at least one nucleotide within the genomic coordinates targeted by an HLA- B guide RNA comprising a guide sequence of SEQ ID NO: 406,.

42. The engineered cell or population of cells of any one of claims 24-41, which has reduced or eliminated surface expression of TRAC relative to an unmodified cell.

43. The engineered cell or population of cells of claim 24-42, comprising a genetic modification in the TRAC gene.

44. The engineered cell or population of cells of claim 43, wherein the gene modification comprises at least one nucleotide within the genomic coordinates chr14:22547524- 22547544, optionally wherein the genetic modification comprises at least one nucleotide within the genomic coordinates targeted by a TRAC guide RNA comprising a guide sequence of SEQ ID NO: 413.

45. The engineered cell or population of cells of any one of claims 24-44, which has reduced or eliminated surface expression of MHC class II relative to an unmodified cell.

46. The engineered cell or population of cells of any one of claims 24-45, further comprising a genetic modification in the CIITA gene, optionally wherein the genetic modification is within the genetic coordinates chosen from: (a) chrl6: 10877363- 10907788 and (b) chr16:10906515-10908136.

47. The engineered cell or population of cells of claim 46, wherein the genetic modification comprises at least one nucleotide within the genomic coordinates chr16:10906643-10906667 orchr16:10907504-10907528, optionally wherein the genetic modification comprises at least one nucleotide within the genomic coordinates targeted by a CIITA guide RNA comprising a guide sequence of SEQ ID NO: 402.WBD (US) 4901-8816-4240vl 36048. The engineered cell or population of cells of any one of claims 24-47, further comprising reduced or eliminated surface expression of TGFBR2 relative to an unmodified cell.

49. The engineered cell or population of cells of any one of claims 24-48, further comprising a genetic modification in the TGFBR2 gene, optionally wherein the genetic modification comprises at least one nucleotide within the genomic coordinates: chr3: 30606864-30691614.

50. The engineered cell or population of cells of claim 49, wherein the genetic modification is within the genomic coordinates chr3:30674205-30674229, optionally wherein the genetic modification comprises at least one nucleotide within the genomic coordinates targeted by a TGFBR2 guide RNA comprising a guide sequence of SEQ ID NO: 301.

51. The engineered cell or population of cells of claim 49, wherein the genetic modification is within the genomic coordinates chr3:30671941-30671961, optionally wherein the genetic modification comprises at least one nucleotide within the genomic coordinates targeted by a TGFBR2 guide RNA comprising a guide sequence of SEQ ID NO: 302.

52. The engineered cell or population of cells of any one of claims 24-51, wherein the genetic modification comprises an indel, a C to T substitution, or an A to G substitution within the genomic coordinates.

53. The engineered cell or population of cells of any one of claims 24-51, wherein the genetic modification comprises an insertion of a heterologous coding sequence.

54. An engineered cell comprising a genetic modification in the HLA-A gene, a modified TRAC gene, and / or a genetic modification in the CIITA gene, wherein the engineered cell expresses an anti-BCMA chimeric antigen receptor (CAR) or comprises a nucleic acid encoding an anti-BCMA CAR.WBD (US) 4901-8816-4240v1 36155. An engineered cell comprising a genetic modification in the HLA-A gene, a genetic modification in the HLA-B gene, a genetic modification in the TRAC gene, and / or a genetic modification in the CIITA gene, wherein the engineered cell expresses an anti-BCMA chimeric antigen receptor (CAR) or comprises a nucleic acid encoding an anti-BCMA CAR.

56. The engineered cell of claim 54 or 55, further comprising a genetic modification in the TGFBR2 gene.

57. The engineered cell or population of cells of any one of claims 24-56, wherein the cell is homozygous for HLA-C, optionally wherein the cell is homozygous for HLA-B and HLA-C.

58. A pharmaceutical composition comprising the engineered cell or population of cells of any one of claims 24-57.

59. The engineered cell, population of cells, or pharmaceutical composition of any one of claims 24-58, wherein the engineered cell is an immune cell.

60. The engineered cell, population of cells, or pharmaceutical composition of any one of claims 24-59, wherein the cell is an NK cell.

61. The engineered cell, population of cells, or pharmaceutical composition of any one of claims 24-60, wherein the cell is a T-cell, optionally wherein the T-cell is a CD4+ T- cell, optionally wherein the T-cell is a CD8+ T-cell, or optionally wherein the T-cell has a T memory stem cell (Tscm) phenotype.

62. The engineered cell, population of cells, or pharmaceutical composition of any one of claims 24-61, wherein the cells are engineered with a genomic editing system.

63. The engineered cell, population of cells, or pharmaceutical composition of claim 62, wherein the genomic editing system comprises an RNA-guided DNA-binding agent or a nucleic acid encoding an RNA-guided DNA-binding agent, optionally wherein the RNA-guided DNA-binding agent or the RNA-guided DNA-binding agentWBD (US) 4901-8816-4240v1 362encoded by the nucleic acid is S. pyogenes Cas9 (SpyCas9), or optionally wherein the RNA-guided DNA-binding agent or the RNA-guided DNA-binding agent encoded by the nucleic acid is N. meningitidis Cas9 (NmeCas9).

64. The engineered cell, population of cells, or pharmaceutical composition of any one of claims 24-63, wherein the guide RNA is provided to the cell in a vector, and / or wherein the RNA-guided DNA-binding agent is provided to the cell in a vector, optionally in the same vector as the guide RNA.

65. The engineered cell, population of cells, or pharmaceutical composition of any one of claims 24-64, wherein the nucleic acid encoding the anti-BCMA CAR is provided to the cell in an expression vector.

66. The engineered cell, population of cells, or pharmaceutical composition of claim 65, wherein the expression vector is a viral vector, optionally wherein the expression vector comprises an AAV vector, and optionally wherein the expression vector comprises SEQ ID NO: 106.

67. The engineered cell, population of cells, or pharmaceutical composition of claim 65, wherein the expression vector is a non-viral vector.

68. The engineered cell, population of cells, or pharmaceutical composition of any one of claims 24-67, wherein the guide RNA is provided to the cell in a lipid nanoparticle (LNP), optionally in the same LNP an RNA-guided DNA-binding agent is provided.

69. The engineered cell, population of cells, or pharmaceutical composition of any one of claims 24-68, wherein the nucleic acid encoding the anti-BCMA CAR is provided to the cell in a lipid nanoparticle (LNP).

70. The engineered cell, population of cells, or pharmaceutical composition of any one of claims 24-69, wherein the cell comprises a genome comprising a nucleic acid of SEQ ID NO: 107.WBD (US) 4901-8816-4240v1 36371. A method of making an engineered cell comprising contacting a cell with:a. the nucleic acid of claim 15 or 17, or the mRNA of claim 16 or 18, or the expression vector of claim 19; andb. at least one genomic editing tool comprising an RNA-guided DNA-binding agent and at least one guide RNA, wherein the at least one guide RNA targets a genomic locus chosen from the HLA-A, HLA-B, TRAC, CIITA, and / or TGFBR2 locus.

72. A method of making an engineered cell comprising an anti-BCMA CAR, comprising a. providing an engineered cell which has reduced or eliminated surface expression of one or more of HLA-A, HLA-B, MHC Class II, and TRAC, and optionally wherein the cell has reduced or eliminated surface expression of TGFBR2, relative to an unmodified cell; andb. contacting the cell with the nucleic acid of claim 15 or 17, or the mRNA of claim 16 or 18, or the expression vector of claim 19.

73. A method of making an engineered cell comprising an anti-BCMA CAR, comprising:(a) contacting the cell with a first lipid nanoparticle (LNP) comprising a base editor and a guide RNA that targets HLA-A,(b) contacting the cell with a second LNP comprising a base editor and a guide RNA that targets HLA-B,(c) contacting the cell with a third LNP comprising a base editor and a guide RNA that targets CIITA,(d) optionally contacting the cell with a fourth LNP comprising a base editor and a guide RNA that targets TGFBR2,(e) contacting the cell with a fifth LNP comprising an mRNA encoding UGI,(f) contacting the cell with a sixth LNP comprising an RNA-guided cleavase and at least one gRNA that is cognate to the RNA-guided cleavase and targets the TRAC locus; and(g) contacting the cell with a nucleic acid encoding an anti-BCMA CAR for insertion into an editing site (e.g., a double strand break) at the TRAC locus.

74. A method of making an engineered cell comprising an anti-BCMA CAR, comprising:(a) contacting a cell with a first population of lipid nanoparticles (LNPs) comprising aWBD (US) 4901-8816-4240v1 364first LNP comprising a base editor and a gRNA that targets the HLA-B locus; optionally a second LNP comprising a base editor and a gRNA that targets the TGFBR2 locus, and a third LNP comprising a uracil glycosylase inhibitor (UGI); (b) contacting a cell with(i) a second population of LNPs comprising a fourth LNP comprising a base editor and a gRNA that targets the HLA-A locus; a fifth LNP comprising a base editor and a gRNA that targets the CIITA locus; a sixth LNP comprising an RNA- guided DNA cleavase and a gRNA that is cognate to the RNA-guide DNA cleavase and targets the TRAC locus, and(ii) a nucleic acid encoding an anti-BCMA CAR for insertion into an editing site (e.g., a double strand break) at the TRAC locus.

75. The method of claim 73 or 74, wherein the RNA-guided cleavase comprises an S. pyogenes (Spy) Cas9 cleavase, and the base editor comprises an N. meningitidis (Nme) Cas9 nickase.

76. A method of administering the engineered cell, population of cells, or pharmaceutical composition of any one of claims 24-70 to a subject in need thereof, or to a subject as an adoptive cell transfer (ACT) therapy.

77. A method of treating a disease or disorder, comprising administering the engineered cell, population of cells, or pharmaceutical composition of any one of claims 24-70 to a subject in need thereof.

78. The method of claim 76 or 77, wherein the engineered cell is allogeneic to the subject.

79. The engineered cell, population of cells, composition, or method of any one of claims 24-70, for use in administration to a subject as an adoptive cell transfer (ACT) therapy, for use in treating a subject having a cancer, for use in treating a subject having an infectious disease, or for use in treating a subject having an autoimmune disease.WBD (US) 4901-8816-4240v1 36580. Use of the engineered cell, population of cells, pharmaceutical composition of any one of claims 24-70, for the manufacture of a medicament for the treatment of a subject having a cancer, an infectious disease, or an autoimmune disease.

81. An engineered cell comprising a genetic modification in the HLA-A gene, a genetic modification in the HLA-B gene, a genetic modification in the TRAC gene, and / or a genetic modification in the CIITA gene, wherein the genetic modification in the HLA-A gene is within the genomic coordinates chr6:29942891-29942915; wherein the genetic modification in the HLA-B gene is within the genomic coordinates chr6:31355222-31355246, chr6:31355221-31355245, or chr6:31355205-31355229; wherein the genetic modification in the TRAC gene is within the genomic coordinates chr14: 22547524-22547544; and wherein the genetic modification in the CIITA gene is within the genomic coordinates chr16: 10906643-10906667; wherein the engineered cell comprises an anti-BCMA chimeric antigen receptor (CAR) or comprises a nucleic acid encoding an anti-BCMA CAR.

82. The engineered cell of claim 81, further comprising a genetic modification in the TGFBR2 gene, wherein the genetic modification in the TGFBR2 gene is within the genomic coordinates chr3:30674205-30674229 or chr3:30671941-30671961.

83. An engineered cell comprising a genetic modification in the HLA-A gene, a genetic modification in the HLA-B gene, a genetic modification in the TRAC gene, and / or a genetic modification in the CIITA gene, wherein the genetic modification in the HLA-A gene is within the genomic coordinates chr6:29942891-29942915; wherein the genetic modification in the HLA-B gene is within the genomic coordinates chr6:31355222-31355246; wherein the genetic modification in the TRAC gene is within the genomic coordinates chr14:22547524-22547544; and wherein the genetic modification in the CIITA gene is within the genomic coordinates chr16: 10906643- 10906667; wherein the engineered cell comprises an anti-BCMA chimeric antigen receptor (CAR) or comprises a nucleic acid encoding an anti-BCMA CAR.WBD (US) 4901-8816-4240v1 36684. The engineered cell of claim 83, further comprising a genetic modification in the TGFBR2 gene, wherein the genetic modification in the TGFBR2 gene is within the genomic coordinates chr3:30674205-30674229.

85. An engineered human T cell comprising multiple genetic modifications and an anti- BCMA chimeric antigen receptor (CAR), wherein(a) the engineered human T cell comprises a genetic modification in the HLA-A gene and reduced or eliminated surface expression of HLA-A relative to an unmodified cell, a genetic modification in the HLA-B gene and reduced or eliminated surface expression of HLA-B relative to an unmodified cell, a genetic modification in the CIITA gene and reduced or eliminated surface expression of MHC class II relative to an unmodified cell, optionally a genetic modification in the TGFBR2 gene and reduced or eliminated surface expression of TGFBR2 relative to an unmodified cell, and(b) the anti-BCMA CAR comprises an antigen-binding domain, or a fragment thereof, that binds to BCMA, wherein the antigen-binding domain comprises a monospecific, bivalent VHH comprising a first heavy chain variable (VH) region and a second VH region each comprising a complementarity determining region 1 (VH CDR1), a VH CDR2, and VH CDR3 as set forth in the amino acid sequences of SEQ ID NO: 63, SEQ ID NO: 65, and SEQ ID NO: 67, respectively, wherein the anti-BCMA CAR is inserted into the TRAC locus.

86. An engineered human T cell comprising multiple genetic modifications and an anti- BCMA chimeric antigen receptor (CAR), wherein(a) the engineered human T cell comprises a genetic modification in the HLA-A gene within the genomic coordinates chr6:29942891-29942915, a genetic modification in the HLA-B gene within the genomic coordinates chr6:31355222-31355246, a genetic modification in the CIITA gene within the genomic coordinates chr16: 10906643- 10906667, optionally a genetic modification in the TGFBR2 gene within the genomic coordinates chr3:30674205-30674229, and(b) the anti-BCMA CAR comprises an antigen-binding domain, that binds to BCMA, wherein the antigen-binding domain comprises a monospecific, bivalent VHH comprising a first heavy chain variable (VH) region and a second VH region each comprising a complementarity determining region 1 (VH CDR1), a VH CDR2, andWBD (US) 4901-8816-4240v1 367VH CDR3 as set forth in the amino acid sequences of SEQ ID NO: 63, SEQ ID NO: 65, and SEQ ID NO: 67, respectively, wherein the anti-BCMA CAR is inserted into the TRAC locus.

87. An engineered human T cell comprising multiple genetic modifications and an anti- BCMA chimeric antigen receptor (CAR), wherein(a) the engineered human T cell comprises a genetic modification in the HLA-A gene within the genomic coordinates chr6:29942891-29942915, a genetic modification in the HLA-B gene within the genomic coordinates chr6:31355222-31355246, a genetic modification in the CIITA gene within the genomic coordinates chr16: 10906643- 10906667, and optionally a genetic modification in the TGFBR2 gene within the genomic coordinates chr3:30674205-30674229, and(b) the anti-BCMA CAR comprises an antigen-binding domain that binds to BCMA, wherein the antigen-binding domain comprises a monospecific, bivalent VHH comprising a first heavy chain variable (VH) region and a second VH region each comprising a complementarity determining region 1 (VH CDR1), a VH CDR2, and VH CDR3 as set forth in the amino acid sequences of SEQ ID NO: 63, SEQ ID NO: 65, and SEQ ID NO: 67, respectively, wherein the anti-BCMA CAR is inserted into the TRAC locus within the genomic coordinates chr14:22547524-22547544.

88. The engineered human T cell of any one of claims 85-87, wherein the first and the second VH region each comprises the amino acid sequence of SEQ ID NO: 81.

89. The engineered human T cell of any one of claims 85-88, wherein the anti-BCMA CAR comprises the amino acid sequence of SEQ ID NO: 83.

90. The engineered human T cell of any one of claims 85-89, wherein the engineered human T cell is a CD4+ or CD8+ T cell.

91. The engineered human T cell of any one of claims 85-90, wherein the engineered human T cell is homozygous for HLA-C, optionally wherein the engineered human T cell is homozygous for HLA-B and for HLA-C.

92. A pharmaceutical composition comprising a population of T cells, wherein the population of T cells comprises CD4+ T cells and / or CD8+ T cells, which compriseWBD (US) 4901-8816-4240v1 368an engineered human T cell comprising multiple genetic modifications and an anti- BCMA chimeric antigen receptor (CAR), wherein(a) the engineered human T cell comprises a genetic modification in the HLA-A gene and reduced or eliminated surface expression of HLA-A relative to an unmodified cell, a genetic modification in the HLA-B gene and reduced or eliminated surface expression of HLA-B relative to an unmodified cell, a genetic modification in the CIITA gene and reduced or eliminated surface expression of MHC class II relative to an unmodified cell, optionally a genetic modification in the TGFBR2 gene and reduced or eliminated surface expression of TGFBR2 relative to an unmodified cell, and(b) the anti-BCMA CAR comprises an antigen-binding domain that binds to BCMA, wherein the antigen-binding domain comprises a monospecific, bivalent VHH comprising a first heavy chain variable (VH) region and a second VH region each comprising a complementarity determining region 1 (VH CDR1), a VH CDR2, and VH CDR3 as set forth in the amino acid sequences of SEQ ID NO: 63, SEQ ID NO: 65, and SEQ ID NO: 67, respectively, wherein the anti-BCMA CAR is inserted into the TRAC locus.

93. A pharmaceutical composition comprising a population of T cells, wherein the population of T cells comprises CD4+ T cells and / or CD8+ T cells, which comprise an engineered human T cell comprising multiple genetic modifications and an anti- BCMA chimeric antigen receptor (CAR), wherein(a) the engineered human T cell comprises a genetic modification in the HLA-A gene within the genomic coordinates chr6:29942891-29942915, a genetic modification in the HLA-B gene within the genomic coordinates chr6:31355222-31355246, a genetic modification in the CIITA gene within the genomic coordinates chr16: 10906643- 10906667, optionally a genetic modification in the TGFBR2 gene within the genomic coordinates chr3:30674205-30674229, and(b) the anti-BCMA CAR comprises an antigen-binding domain that binds to BCMA, wherein the antigen-binding domain comprises a monospecific, bivalent VHH comprising a first heavy chain variable (VH) region and a second VH region each comprising a complementarity determining region 1 (VH CDR1), a VH CDR2, and VH CDR3 as set forth in the amino acid sequences of SEQ ID NO: 63, SEQ ID NO:WBD (US) 4901-8816-4240v1 36965, and SEQ ID NO: 67, respectively, wherein the anti-BCMA CAR is inserted into the TRAC locus.

94. A pharmaceutical composition comprising a population of T cells, wherein the population of T cells comprises CD4+ T cells and / or CD8+ T cells, which comprise an engineered human T cell comprising multiple genetic modifications and an anti- BCMA chimeric antigen receptor (CAR), wherein(a) the engineered human T cell comprises a genetic modification in the HLA-A gene within the genomic coordinates chr6:29942891-29942915, a genetic modification in the HLA-B gene within the genomic coordinates chr6:31355222-31355246, a genetic modification in the CIITA gene within the genomic coordinates chr16: 10906643- 10906667, optionally a genetic modification in the TGFBR2 gene within the genomic coordinates chr3:30674205-30674229, and(b) the anti-BCMA CAR comprises an antigen-binding domain that binds to BCMA, wherein the antigen-binding domain comprises a monospecific, bivalent VHH comprising a first heavy chain variable (VH) region and a second VH region each comprising a complementarity determining region 1 (VH CDR1), a VH CDR2, and VH CDR3 as set forth in the amino acid sequences of SEQ ID NO: 63, SEQ ID NO: 65, and SEQ ID NO: 67, respectively, wherein the anti-BCMA CAR is inserted into the TRAC locus within the genomic coordinates chr14:22547524-22547544.

95. The pharmaceutical composition of any one of claims 92-94, wherein the first and the second VH region each comprises the amino acid sequence of SEQ ID NO: 81.

96. The pharmaceutical composition of any one of claims 92-95, wherein the anti-BCMA CAR comprises the amino acid sequence of SEQ ID NO: 83.

97. The pharmaceutical composition of any one of claims 92-96, wherein the engineered human T cell is homozygous for HLA-C; optionally wherein the engineered human T cell is homozygous for HLA-B and for HLA-C.

98. A method of administering the engineered human T cell or pharmaceutical composition of any one of claims 85-97 to a subject in need thereof, or to a subject as an adoptive cell transfer (ACT) therapy.WBD (US) 4901-8816-4240v1 37099. A method of treating a disease or disorder, comprising administering the engineered human T cell or pharmaceutical composition of any one of claims 85-97 to a subject in need thereof.

100. The engineered human T cell or pharmaceutical composition of any one of claims 85-97, for use in administration to a subject as an adoptive cell transfer (ACT) therapy, for use in treating a subject having a cancer, or for use in treating a subject having an autoimmune disease.

101. The engineered human T cell or pharmaceutical composition of claim 100, wherein the disease or disorder is a cancer.

102. The engineered human T cell or pharmaceutical composition for use of claim 101, wherein the cancer is a solid tumor or a hematological malignancy.

103. The engineered human T cell or pharmaceutical composition for use or the method of claim 102, wherein the hematological malignancy is multiple myeloma.

104. The engineered human T cell or pharmaceutical composition for use or the method of claim 99, wherein the disease or disorder is a B cell or plasma cell autoimmune disease, such as myasthenia gravis (MG), systemic lupus erythematosus (SLE), and neuromyelitis optica spectrum disorder (NMOSD), idiopathic inflammatory myopathy (IIM), multiple sclerosis (MS), primary Sjogren's syndrome (PSS), or stiff person syndrome (SPS).

105. A viral vector comprising the nucleic acid sequence of SEQ ID NO: 106.WBD (US) 4901-8816-4240vl 371

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