Materials and methods for treating myeloid neoplasms

Abstract

This document provides methods and materials involved in treating myeloid neoplasms (e.g., myeloid cancers such as acute myeloid leukemia (AML)). For example, methods and materials for making and / or using T cells expressing (e.g., engineered to express) (a) one or more chimeric antigen receptors (CARs) having the ability to bind to a myeloid-specific polypeptide (e.g., a CD33 polypeptide) and (b) one or more inhibitory CARs (iCARs) having the ability to bind to a class I major histocompatibility complex (MHC) polypeptide (e.g., an HLA-A polypeptide such as an HLA-A2 polypeptide). In some cases, T cells provided herein can be administered to a mammal (e.g., a human) having a myeloid neoplasm (e.g., a myeloid cancer such as AML) and having received a haploidentical bone marrow transplant to target (e.g., target and destroy) the mammal's myeloid cells while sparing the donor-derived myeloid cells.

Description

[0001]Attorney Docket No.44807-0483WO1 / P18190-01 MATERIALS AND METHODS FOR TREATING MYELOID NEOPLASMS CROSS-REFERENCETORELATEDAPPLICATIONSThis application claims the benefit of U.S. Patent Application Serial No.63 / 662,500, filed on June 21, 2024. The disclosure of the prior application is considered part of, and is incorporated by reference in, the disclosure of this application. STATEMENTREGARDINGFEDERALFUNDINGThis invention was made with government support under grant CA006973 awarded by the National Institutes of Health. The government has certain rights in the invention. SEQUENCELISTINGThis application contains a Sequence Listing that has been submitted electronically as an XML file named “44807-0483WO1_SL.xml.” The XML file, created on June 3, 2025, is 49,864 bytes in size. The material in the XML file is hereby incorporated by reference in its entirety. TECHNICAL FIELD This document relates to methods and materials involved in treating myeloid neoplasms (e.g., myeloid cancers such as acute myeloid leukemia (AML)). For example, this document provides methods and materials for making and / or using T cells expressing (e.g., engineered to express) (a) one or more chimeric antigen receptors (CARs) having the ability to bind to a myeloid-specific polypeptide (e.g., a CD33 polypeptide) and (b) one or more inhibitory CARs (iCARs) having the ability to bind to a class I major histocompatibility complex (MHC) polypeptide (e.g., an HLA-A polypeptide such as an HLA-A2 polypeptide). In some cases, T cells provided herein can be administered to a mammal (e.g., a human) having a myeloid neoplasm (e.g., a myeloid cancer such as AML) and having received a haploidentical bone marrow transplant to target (e.g., target and destroy) the mammal’s myeloid cells while sparing the donor-derived myeloid cells. Attorney Docket No.44807-0483WO1 / P18190-01 BACKGROUND AML patients who undergo bone marrow transplant and relapse post-transplant have few clinical treatment options. Although bone marrow transplant can provide a cure for AML patients, 30-50% of patients relapse post-transplant (Döhner et al., Blood, 129(4):424–447 (2017); Gooley et al., N Engl J Med., 363(22):2091-101 (2910); Kreidieh et al., Int J Hematol., 116:330–340 (2022); Horowitz et al., Bone Marrow Transplant, 53:1379–1389 (2018); Thol et al., Curr Treat Options Oncol., 21:66 (2020); and Bejanyan et al., Biol Blood Marrow Transplant 21:454–9 (2015)). Additionally, the outcomes for these patients that relapse post-transplant is poor, with a 3-year overall survival rate of 4% for patients that relapse within 6 months of transplant, 12% for relapse between 6 months and 2 years post- transplant, 26% for relapse between 2- and 3-years post-transplant, and 38% for relapse occurring more than 3 years post-transplant (Bejanyan et al., Biol Blood Marrow Transplant 21:454–9 (2015); Schmid et al., Haematologica 103:237–245 (2018); and Döhner et al., Blood, 129(4):424–447 (2017)). For those patients that do relapse, treatment options may include donor lymphocyte infusion or a second bone marrow transplant, but these therapies pose significant risks to the patient in terms of morbidity and mortality. Additionally, these therapies require that the patient relapsed more than 6 months after initial bone marrow transplant and that there was not graft-vs-host disease due to the initial transplant (Ruutu et al., Bone Marrow Transplant., 50(12):1542-50 (2015); Kreidieh et al., Int J Hematol., 116:330–340 (2022); Thol et al., Curr Treat Options Oncol., 21:66 (2020); and Bejanyan et al., Biol Blood Marrow Transplant 21:454–9 (2015)). Other treatment options for relapsed patients include chemotherapy agents, which have associated toxicities, and FLT3 inhibitors, which are only options for patients with FLT3 mutations and are usually used as first-line therapeutics (Kreidieh et al., Int J Hematol., 116:330–340 (2022); and Thol et al., Curr Treat Options Oncol., 21:66 (2020)). SUMMARY This document provides methods and materials involved in treating myeloid neoplasms (e.g., myeloid cancers such as AML). For example, this document provides T cells (e.g., CAR T cells) expressing (e.g., engineered to express) (a) one or more CARs having the Attorney Docket No.44807-0483WO1 / P18190-01 ability to bind to a myeloid-specific polypeptide (e.g., a CD33 polypeptide) and (b) one or more iCARs having the ability to bind to a class I MHC polypeptide (e.g., an HLA-A polypeptide such as an HLA-A2 polypeptide). In some cases, a T cell engineered to express (a) one or more CARs having the ability to bind to a myeloid-specific polypeptide (e.g., a CD33 polypeptide) and (b) one or more iCARs having the ability to bind to a class I MHC polypeptide (e.g., an HLA-A polypeptide such as an HLA-A2 polypeptide) can include (e.g., can be engineered to include) (a) a nucleic acid sequence encoding one or more CARs having the ability to bind to a myeloid-specific polypeptide (e.g., a CD33 polypeptide) and (b) a nucleic acid sequence encoding one or more iCARs having the ability to bind to a class I MHC polypeptide (e.g., an HLA-A polypeptide such as an HLA-A2 polypeptide), such that the T cells express the CAR(s) having the ability to bind to the CD33 polypeptide and express the iCAR(s) having the ability to bind to the class I MHC polypeptide. A T cell that expresses one or more CARs can also be referred to herein as a CAR T cell or a CAR+T cell. For example, a T cell that expresses one or more CARs having the ability to bind to a CD33 polypeptide can also be referred to herein as a CD33 CAR+T cell or a CD33-CAR+T. A T cell that expresses one or more iCARs can also be referred to herein as an iCAR T cell or an iCAR+T cell. For example, a T cell that expresses one or more iCARs having the ability to bind to an HLA-A2 polypeptide can also be referred to herein as an HLA-A2 iCAR T cell or an HLA-A2 iCAR+T cell. This document also provides methods for treating mammals (e.g., humans) having a myeloid neoplasm (e.g., a myeloid cancer such as AML). When a mammal (e.g., a human) having a myeloid neoplasm (e.g., a myeloid cancer such as AML) receives a haploidentical bone marrow transplant, an HLA-A mismatch exists between the cells produced by the mammal’s bone marrow (also referred to as recipient-derived myeloid cells) and cells produced by the transplanted bone marrow (also referred to as donor-derived myeloid cells) such that the recipient-derived myeloid cells can have one HLA-A haplotype while donor- derived myeloid cells can have another HLA-A haplotype (Luznik et al., Biol. Blood Marrow Transplant., 14(6):641-50 (2008); Anasetti et al., N. Engl. J. Med., 320(4):197-204 (1989); Munn et al., Bone Marrow Transplant 19:421–427 (1997)). As described herein, an HLA-A mismatch resulting from a haploidentical bone marrow transplant can be used to target an Attorney Docket No.44807-0483WO1 / P18190-01 adoptive cell therapy (e.g., a CAR T cell therapy) to recipient-derived myeloid cells (e.g., neoplastic myeloid cells) within a mammal having received a bone marrow transplant while sparing donor-derived myeloid cells (e.g., healthy myeloid cells). In some cases, a mammal (e.g., a human) having a myeloid neoplasm (e.g., a myeloid cancer such as AML) and having been administered a haploidentical bone marrow transplant can be administered a composition containing one or more T cells (e.g., CAR T cells) expressing (e.g., engineered to express) (a) one or more CARs having the ability to bind to a myeloid-specific polypeptide (e.g., a CD33 polypeptide) and (b) one or more iCARs having the ability to bind to a class I MHC polypeptide (e.g., an HLA-A polypeptide) present on donor-derived myeloid cells but not present on the mammal’s cells (e.g., neoplastic myeloid cells) to treat the myeloid neoplasm. For example, when a mammal having a myeloid neoplasm (e.g., a myeloid cancer such as AML) and having an HLA-A1 / A3 haplotype receives a haploidentical bone marrow transplant from a donor having an HLA-A2 / A3 haplotype, an HLA-A2 mismatch exists between the cells produced by the mammal’s bone marrow and the donor-derived myeloid cells such that an adoptive cell therapy including CAR T cells including (e.g., designed to include) (a) a CAR having the ability to bind a CD33 polypeptide and (b) an iCAR having the ability to bind an HLA-A2 polypeptide can target (e.g., target and destroy) the neoplastic myeloid cells produced by the mammal’s bone marrow while sparing the healthy donor- derived myeloid cells. In such cases, when a CD33 CAR+HLA-A2 iCAR+T cell is bound to a donor-derived myeloid cell (e.g., a healthy myeloid cell) via both the CD33 CAR and the HLA-A2 iCAR, the HLA-A2 iCAR can suppress activation of the CD33 CAR+HLA-A2 iCAR+T cell via the CD33 CAR. However, when a CD33 CAR+HLA-A2 iCAR+T cell is bound to a neoplastic myeloid cell (e.g., a myeloid cancer cell such as an AML cell) via only the CD33 CAR (e.g., in the absence of any HLA-A2 polypeptide), the HLA-A2 iCAR does not suppress T cell activation via the CD33 CAR and the CD33 CAR+HLA-A2 iCAR+T cell can target (e.g., target and destroy) the bound neoplastic myeloid cells (e.g., the bound myeloid cancer cell such as a bound AML cell). Having the ability to treat a mammal (e.g., a human) having a myeloid neoplasm (e.g., a myeloid cancer such as AML) and having received a haploidentical bone marrow transplant as described herein (e.g., by administering an adoptive cell therapy including one Attorney Docket No.44807-0483WO1 / P18190-01 or more T cells (e.g., CAR T) cells expressing (e.g., engineered to express) (a) one or more CARs having the ability to bind to a myeloid-specific polypeptide (e.g., a CD33 polypeptide) and (b) one or more iCARs having the ability to bind to a class I MHC polypeptide (e.g., an HLA-A polypeptide such as an HLA-A2 polypeptide)) provides a unique and unrealized opportunity to specifically target (e.g., target and destroy) myeloid cells (e.g., neoplastic myeloid cells) within the mammal without harming donor-derived myeloid cells (e.g., healthy myeloid cells) being produced by the transplanted bone marrow. In general, one aspect of this document features T cells including (a) a nucleic acid encoding a CAR that binds a myeloid-specific polypeptide present on a myeloid cell, where the T cells expresses the CAR, and (b) a nucleic acid encoding an iCAR that binds an HLA-A polypeptide, where the T cell expresses the iCAR, and where the iCAR, when bound to the HLA-A polypeptide, suppresses activation of the T cell. The myeloid-specific marker can be a CD33 polypeptide. The CAR can include (i) a heavy chain variable (VH) domain having a VH CDR1 that comprises, consists essentially of, or consists of the amino acid sequence set forth in SEQ ID NO:2, a VH CDR2 that comprises, consists essentially of, or consists of the amino acid sequence set forth in SEQ ID NO:3, and a VH CDR3 that comprises, consists essentially of, or consists of the amino acid sequence set forth in SEQ ID NO:4 and / or (ii) a light chain variable (VL) domain having a VL CDR1 that comprises, consists essentially of, or consists of the amino acid sequence set forth in SEQ ID NO:5, a VL CDR2 that comprises, consists essentially of, or consists of the amino acid sequence set forth in SEQ ID NO:6, and a VL CDR3 that comprises, consists essentially of, or consists of the amino acid sequence set forth in SEQ ID NO:7. The CAR can include (i) and (ii). The CAR can include a CD28 stimulatory intracellular signaling domain or a CD3ζ stimulatory intracellular signaling domain. The HLA-A polypeptide can be an HLA-A2 polypeptide. The CAR can be a TCR CAR. The iCAR can include (iii) a VH domain comprising a VH CDR1 that comprises, consists essentially of, or consists of the amino acid sequence set forth in SEQ ID NO:9, a VH CDR2 that comprises, consists essentially of, or consists of the amino acid sequence set forth in SEQ ID NO:10, and a VH CDR3 that comprises, consists essentially of, or consists of the amino acid sequence set forth in SEQ ID NO:11 and / or (iv) VL domain comprising a VL CDR1 that comprises, consists essentially of, or consists of the amino acid sequence set Attorney Docket No.44807-0483WO1 / P18190-01 forth in SEQ ID NO:12, a VL CDR2 that comprises, consists essentially of, or consists of the amino acid sequence set forth in SEQ ID NO:13, and a VL CDR3 that comprises, consists essentially of, or consists of the amino acid sequence set forth in SEQ ID NO:14. The iCAR can include (iii) and (iv). The iCAR can include a PD-1 inhibitory intracellular signaling domain or a LIR-1 inhibitory intracellular signaling domain. The T cell can be obtained from a human. In another aspect, this document features methods for treating a mammal having a myeloid neoplasm and having received a haploidentical bone marrow transplant. The methods can include, or consist essentially of, administering, to a mammal having a myeloid neoplasm and having received a haploidentical bone marrow transplant, a composition including T cells including (a) a nucleic acid encoding a CAR that binds a myeloid-specific polypeptide present on a myeloid cell, where the T cell expresses the CAR, and (b) a nucleic acid encoding an iCAR that binds an HLA-A polypeptide, where the T cells expresses the iCAR, and where the iCAR, when bound to the HLA-A polypeptide, suppresses activation of the T cell. The myeloid-specific marker can be a CD33 polypeptide, where the HLA-A polypeptide is present on a myeloid cell produced by the transplanted bone marrow but is not present on a myeloid cell produced by the mammal’s bone marrow. The mammal can be a human. The myeloid neoplasm can be an acute myeloid leukemia (AML), a myeloid sarcoma, a chronic myelogenous leukemia (CML), a chronic myelomonocytic leukemia (CMML), an acute promyelocytic leukemia (APL), a juvenile myelomonocytic leukemia (JMML), a myelodysplastic syndrome, a polycythemia vera, an essential thrombocythemia, a primary myelofibrosis, a chronic neutrophilic leukemia, or a chronic eosinophilic leukemia. The CAR can include (i) a VH domain having a VH CDR1 that comprises, consists essentially of, or consists of the amino acid sequence set forth in SEQ ID NO:2, a VH CDR2 that comprises, consists essentially of, or consists of the amino acid sequence set forth in SEQ ID NO:3, and a VH CDR3 that comprises, consists essentially of, or consists of the amino acid sequence set forth in SEQ ID NO:4 and / or (ii) a VL domain having a VL CDR1 that comprises, consists essentially of, or consists of the amino acid sequence set forth in SEQ ID NO:5, a VL CDR2 that comprises, consists essentially of, or consists of the amino acid sequence set forth in SEQ ID NO:6, and a VL CDR3 that comprises, consists essentially Attorney Docket No.44807-0483WO1 / P18190-01 of, or consists of the amino acid sequence set forth in SEQ ID NO:7. The CAR can include (i) and (ii). The CAR can include a CD28 stimulatory intracellular signaling domain or a CD3ζ stimulatory intracellular signaling domain. The HLA-A polypeptide can be an HLA- A2 polypeptide. The iCAR can include (iii) a VH domain having a VH CDR1 that comprises, consists essentially of, or consists of the amino acid sequence set forth in SEQ ID NO:9, a VH CDR2 that comprises, consists essentially of, or consists of the amino acid sequence set forth in SEQ ID NO:10, and a VH CDR3 that comprises, consists essentially of, or consists of the amino acid sequence set forth in SEQ ID NO:11 and / or (iv) VL domain having a VL CDR1 that comprises, consists essentially of, or consists of the amino acid sequence set forth in SEQ ID NO:12, a VL CDR2 that comprises, consists essentially of, or consists of the amino acid sequence set forth in SEQ ID NO:13, and a VL CDR3 that comprises, consists essentially of, or consists of the amino acid sequence set forth in SEQ ID NO:14. The iCAR can include (iii) and (iv). The iCAR can include a PD-1 inhibitory intracellular signaling domain or a LIR-1 inhibitory intracellular signaling domain. Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains. Although methods and materials similar or equivalent to those described herein can be used to practice the invention, suitable methods and materials are described below. All publications, patent applications, patents, and other references mentioned herein are incorporated by reference in their entirety. In case of conflict, the present specification, including definitions, will control. In addition, the materials, methods, and examples are illustrative only and not intended to be limiting. The details of one or more embodiments of the invention are set forth in the accompanying drawings and the description below. Other features, objects, and advantages of the invention will be apparent from the description and drawings, and from the claims. BRIEF DESCRIPTION OF THE DRAWINGS Figure 1. Schematic of an exemplary CD33-CAR+and HLA-A2 iCAR+T cell. CAR and iCAR constructs were knocked into a primary T cell genome using CRISPR. The CAR and iCAR were expressed on the cell surface of the T cell. Attorney Docket No.44807-0483WO1 / P18190-01 Figures 2A – 2B. Screen of CD33-CAR Constructs. Constructs were cloned and then in vitro transcribed. The RNA was then transfected into T cells and the T cells were co- cultured with acute myeloid leukemia (AML) cells. The number of target cells remaining at the end of co-culture was measured via flow cytometry and then normalized to wells with mock electroporated T cells. Figure 2A) Proportion of remaining target cells after 56-hour co-culture with CD33-CAR+T cells. Figure 2B) Proportion of remaining HL-60 target cells after 40-hour co-culture with CD33-CAR+T cells. Figure 3. Screen of CD33-T cell receptor (TCR) CAR constructs. TCR CAR constructs, as well as a few CAR constructs, were cloned into homology-directed repair templates and knocked into primary T cells via CRISPR. Edited CD33 TCR CAR or CD33 CAR knock-in (KI) T cells were co-cultured with HL-60 AML cells for 60 hours. The number of target cells remaining at the end of co-culture was measured via flow cytometry and then normalized to wells with T cells that had a TCR knockout (TRAC / TRBC KO). Figures 4A – 4B. Schematics of exemplary homology-directed repair templates (HDRTs) for generating CAR+and iCAR+T cells. CAR and iCAR constructs were knocked into the TRAC locus using an EF-1α promoter and 2A sequences between components to allow for translational cleavage of the polycistronic transcript produced by the construct. Constructs are referred to by the order of the CAR and iCAR components in their HDRT. Figure 4A) A schematic of a construct including a nucleic acid sequence encoding a CAR followed by a nucleic acid sequence encoding an iCAR in a polycistronic transcript. Figure 4B) A schematic of a construct including a nucleic acid sequence encoding an iCAR followed by a nucleic acid sequence encoding a CAR in a polycistronic transcript. Figure 5. IFN-γ expression in co-cultures of CAR+iCAR T cells with AML cells. CAR and iCAR constructs were knocked into primary T cells and edited cells were co- cultured with THP-1 AML cell lines for 44 hours. At the end of co-culture, media was extracted and IFN-γ expression was determined using ELISA. The IFN-γ expression was measured in media as indicated. Figures 6A – 6G. IFN-γ expression in co-cultures of CAR+iCAR T cells with THP-1 AML cells. CAR and iCAR constructs were knocked into primary T cells and edited cells were co-cultured with AML cell lines. At the end of co-culture, media was extracted and Attorney Docket No.44807-0483WO1 / P18190-01 IFN-γ expression was determined using ELISA. The IFN-γ expression was measured in media as indicated. Figure 6A) IFN-γ expression after 40-hour co-cultures with edited SCO8 (HLA A2 / A3) T cells. Figure 6B) IFN-γ expression after 40-hour co-cultures with edited ACO4 (HLA A24 / A31) T cells. Figure 6C) IFN-γ expression after 40-hour co-cultures with edited SCO9 (HLA A1 / A2) T cells. Figure 6D) IFN-γ expression after 40-hour co-cultures with edited ACO2 (HLA A2 / A3) T cells. Figure 6E) IFN-γ expression after 40-hour co- cultures with edited ACO3 (HLA A2 / A3) T cells. Figure 6F) IFN-γ expression after 40-hour co-cultures with edited ACO5 (HLA A2 / A3) T cells. Figure 6G) IFN-γ expression after 40- hour co-cultures with edited ACO6 (HLA A2 / A3) T cells. Figure 7. Cytotoxicity of selected CAR+iCAR constructs in co-cultures with THP-1 AML cell lines. Primary T cells underwent CRISPR knock-in to express the CAR and iCAR constructs and edited T cells were co-cultured with THP-1 AML cell lines for 44 hours. The number of THP-1 target cells remaining at the end of co-culture was measured via flow cytometry and then normalized using counting beads. Figures 8A – 8G. Cytotoxicity of selected CAR+iCAR constructs in primary T cells. Primary healthy donor T cells underwent CRISPR knock-in to express the CAR and iCAR constructs and edited T cells were co-cultured with THP-1 AML cell lines for 40 hours. The number of THP-1 AML target cells remaining at the end of co-culture was measured via flow cytometry and then normalized using counting beads. Figure 8A) Cytotoxicity after 40-hour co-cultures with edited SCO8 (HLA A2 / A3) T cells. Figure 8B) Cytotoxicity after 40-hour co-cultures with edited ACO4 (HLA A24 / A31) T cells. Figure 8C) Cytotoxicity after 40- hour co-cultures with edited SCO9 (HLA A1 / A2) T cells. Figure 8D) Cytotoxicity after 40- hour co-cultures with edited ACO2 (HLA A2 / A3) T cells. Figure 8E) Cytotoxicity after 40- hour co-cultures with edited ACO3 (HLA A2 / A3) T cells. Figure 8F) Cytotoxicity after 40- hour co-cultures with edited ACO5 (HLA A2 / A3) T cells. Figure 8G) Cytotoxicity after 40- hour co-cultures with edited ACO6 (HLA A2 / A3) T cells. Figures 9A - 9B. Cytotoxicity of a selected CAR+iCAR construct in co-culture with HL-60 and MOLM-14 AML cell lines. Primary T cells underwent CRISPR knock-in to express the CAR and iCAR constructs and edited T cells were co-cultured with either HL-60 (Figure 9A) or MOLM-14 (Figure 9B) AML cell lines for 40 hours. The number of HL-60 or Attorney Docket No.44807-0483WO1 / P18190-01 MOLM-14 AML target cells remaining at the end of co-culture was measured via flow cytometry and then normalized using counting beads. Figures 10A - 10B. IFN-γ expression in co-cultures of CAR+iCAR T cells with HL- 60 or MOLM-14 AML cells. CAR and iCAR constructs were knocked into primary T cells and edited cells were co-cultured with either HL-60 (Figure 10A) or MOLM-14 (Figure 10B) AML cell lines for 40 hours. At the end of co-culture, media was extracted and IFN-γ expression was determined using ELISA. The IFN-γ expression was measured in media as indicated in each Figure. Figure 11. Screen of CD33-CAR Constructs. Constructs were cloned into homology- directed repair templates and knocked into primary T cells via CRISPR. T cells were co- cultured with acute myeloid leukemia (AML) cells. The number of target cells remaining at the end of the 40-hour co-culture was measured via flow cytometry and then normalized to wells with T cells that had a TCR knockout (TRAC / TRBC KO) to calculate cytotoxicity. Figures 12A-12B. Screen of CD33-T cell receptor (TCR) CAR constructs. TCR CAR constructs were cloned into homology-directed repair templates and knocked into primary T cells via CRISPR. Edited CD33 TCR CAR KI T cells were co-cultured with HL-60 AML cells for 60 hours. Figure 12A) The number of target cells remaining at the end of co-culture was measured via flow cytometry and then normalized to wells with T cells that had a TCR knockout (TRAC / TRBC KO) to calculate cytotoxicity. Figure 12B) At the end of co-culture, media was extracted and IFN-γ expression was determined using ELISA. The IFN-γ expression was measured in media as indicated. Figure 13. Screen of CAR+iCAR T cells with AML cells. HDRTs of CAR and iCAR constructs were cloned and then knocked into primary T cells using CRISPR. Edited T cells were co-cultured with HL-60 AML cell lines for 40 hours. The number of target cells remaining at the end of co-culture was measured via flow cytometry and then normalized to wells with T cells that had a TCR knockout (TRAC / TRBC KO) to calculate cytotoxicity. Figure 14. Cytotoxicity of selected CAR+iCAR construct in co-culture with mixed HL-60 AML cell lines. Primary T cells underwent CRISPR knock-in to express the CAR and iCAR constructs. Edited T cells were co-cultured with mixed HL-60 AML cell lines for 60 Attorney Docket No.44807-0483WO1 / P18190-01 hours. The number of HL-60 target cells remaining at the end of co-culture was measured via flow cytometry and then normalized using counting beads and wells with unedited T cells. Figures 15A – 15C. Cytotoxicity of a selected CAR+iCAR construct with the addition of “CoSTAR” (MyD88 and CD40) co-stimulatory domains in co-culture with HL- 60, OCI-M1, and MOLM-14 AML cell lines. Primary T cells underwent CRISPR knock-in to express the CAR, CoSTAR, and iCAR constructs. Edited T cells were co-cultured with either HL-60 (Figure 15A), OCI-M1 (Figure 15B) or MOLM-14 (Figure 15C) AML cell lines for 40 hours. The number of HL-60, OCI-M1 or MOLM-14 AML target cells remaining at the end of co-culture was measured via flow cytometry and then normalized to counting beads and wells with T cells that had a TCR knockout (TRAC / TRBC KO) to calculate cytotoxicity. Figures 16A – 16C. IFN-γ expression in co-cultures of T cells containing CAR+iCAR constructs with the addition of “CoSTAR” (MyD88 and CD40) co-stimulatory domains, with HL-60, OCI-M1, or MOLM-14 AML cells. CAR, CoSTAR, and iCAR constructs were knocked into primary T cells and edited cells were co-cultured with either HL-60 (Figure 16A), OCI-M1 (Figure 16B), or MOLM-14 (Figure 16C) AML cell lines for 40 hours. At the end of co-culture, media was extracted and IFN-γ expression was determined using ELISA. The IFN-γ expression was measured in media as indicated in each Figure. Figure 17. Cytotoxicity of selected CAR+iCAR construct with the addition of “CoSTAR” (MyD88 and CD40) co-stimulatory domains in co-culture with mixed OC1-M1 AML cell lines. Primary T cells underwent CRISPR knock-in to express the CAR, CoSTAR, and iCAR constructs. Edited T cells were co-cultured with mixed OCI-M1 AML cell lines for 40 hours. The number of OCI-M1 target cells remaining at the end of co-culture was measured via flow cytometry and then normalized using counting beads and wells with T cells that had a TCR knockout (TRAC / TRBC KO). Figure 18. Presence of HLA-A2+ and HLA-A2- HL-60 cells in peripheral blood collected from mice treated with CAR+iCAR T cells. Female NSG mice were injected with equal numbers of HL-60 AML cells that were either HLA-A2+ or HLA-A2-. HDRTs of CAR and iCAR constructs were cloned and then knocked into primary T cells using CRISPR. Edited T cells were then injected into HL-60 xenograft mice. Peripheral blood was Attorney Docket No.44807-0483WO1 / P18190-01 collected from submandibular veins of the mice and analyzed via flow cytometry for the presence of HLA-A2+ and HLA-A2- HL-60 cells. Figure 19. Radiance of HL-60 HLA-A2- cells in mice treated with CAR+iCAR T cells. Female NSG mice were injected with equal numbers of HL-60 AML cells that were either HLA-A2+ or HLA-A2-. HDRTs of CAR and iCAR constructs were cloned and then knocked into primary T cells using CRISPR. Edited T cells were then injected into HL-60 xenograft mice. Burden of HL-60 HLA-A2- cancer cells was assessed by quantifying bioluminescence signal using an In Vivo Imaging System. Figure 20. Presence of HLA-A2+ and HLA-A2- HL-60 cells in spleens collected from mice treated with CAR+iCAR T cells. Female NSG mice were injected with equal numbers of HL-60 AML cells that were either HLA-A2+ or HLA-A2-. HDRTs of CAR and iCAR constructs were cloned and then knocked into primary T cells using CRISPR. Edited T cells were then injected into HL-60 xenograft mice. After 31 days, mice were euthanized, and spleens were collected. Spleens were analyzed via flow cytometry for the presence of HLA-A2+ and HLA-A2- HL-60 cells and counts were normalized to the weight of the spleens collected. Figure 21. Presence of human T cell in spleens collected from mice treated with CAR+iCAR T cells. Female NSG mice were injected with equal numbers of HL-60 AML cells that were either HLA-A2+ or HLA-A2-. HDRTs of CAR and iCAR constructs were cloned and then knocked into primary T cells using CRISPR. Edited T cells were then injected into HL-60 xenograft mice. After 31 days, mice were euthanized, and spleens were collected. Spleens were analyzed via flow cytometry for the presence of human T cells and counts were normalized to the weight of the spleens collected Figure 22. Presence of HLA-A2+ and HLA-A2- HL-60 cells in bone marrow collected from mice treated with CAR+iCAR T cells. Female NSG mice were injected with equal numbers of HL-60 AML cells that were either HLA-A2+ or HLA-A2-. HDRTs of CAR and iCAR constructs were cloned and then knocked into primary T cells using CRISPR. Edited T cells were then injected into HL-60 xenograft mice. After 31 days, mice were euthanized, and bone marrow was collected from the femurs of the mice. Bone marrow was analyzed via flow cytometry for the presence of HLA-A2+ and HLA-A2- HL-60 cells. Attorney Docket No.44807-0483WO1 / P18190-01 Figure 23. Presence of human T cells in bone marrow collected from mice treated with CAR+iCAR T cells. Female NSG mice were injected with equal numbers of HL-60 AML cells that were either HLA-A2+ or HLA-A2-. HDRTs of CAR and iCAR constructs were cloned and then knocked into primary T cells using CRISPR. Edited T cells were then injected into HL-60 xenograft mice. After 31 days, mice were euthanized, and bone marrow was collected from the femurs of the mice. Bone marrow was analyzed via flow cytometry for the presence of human T cells. Figure 24. Presence of HLA-A2+ and HLA-A2- HL-60 cells in peripheral blood collected from mice treated with T cells containing CAR+iCAR constructs with the addition of “CoSTAR” (MyD88 and CD40) co-stimulatory domains. Female NSG mice were injected with equal numbers of HL-60 AML cells that were either HLA-A2+ or HLA-A2-. HDRTs of CAR, CoSTAR, and iCAR constructs were cloned and then knocked into primary T cells using CRISPR. Edited T cells were then injected into HL-60 xenograft mice. Peripheral blood was collected from submandibular veins of the mice and analyzed via flow cytometry for the presence of HLA-A2+ and HLA-A2- HL-60 cells. Figure 25. Presence of human T cells in peripheral blood collected from mice treated with T cells containing CAR+iCAR constructs with the addition of “CoSTAR” (MyD88 and CD40) co-stimulatory domains. Female NSG mice were injected with equal numbers of HL- 60 AML cells that were either HLA-A2+ or HLA-A2-. HDRTs of CAR, CoSTAR, and iCAR constructs were cloned and then knocked into primary T cells using CRISPR. Edited T cells were then injected into HL-60 xenograft mice. Peripheral blood was collected from submandibular veins of the mice and analyzed via flow cytometry for the presence of human T cells. Figure 26. Radiance of HL-60 HLA-A2- cells in mice treated with T cells containing CAR+iCAR constructs with the addition of “CoSTAR” (MyD88 and CD40) co-stimulatory domains. Female NSG mice were injected with equal numbers of HL-60 AML cells that were either HLA-A2+ or HLA-A2-. HDRTs of CAR and iCAR constructs were cloned and then knocked into primary T cells using CRISPR. Edited T cells were then injected into HL- 60 xenograft mice. Burden of HL-60 HLA-A2- cancer cells was assessed by quantifying bioluminescence signal using an In Vivo Imaging System. Attorney Docket No.44807-0483WO1 / P18190-01 DETAILED DESCRIPTION This document provides methods and materials for generating T cells (e.g., CAR T cells) expressing (e.g., engineered to express) (a) one or more CARs having the ability to bind to a myeloid-specific polypeptide (e.g., a CD33 polypeptide) and (b) one or more iCARs having the ability to bind to a class I MHC polypeptide (e.g., an HLA-A polypeptide such as an HLA-A2 polypeptide). In some cases, CARs that can bind a myeloid-specific polypeptide can include (a) an antigen-binding domain that binds the myeloid-specific polypeptide, (b) a transmembrane domain, and (c) one or more stimulatory intracellular signaling domains. For example, a T cell engineered to express a CAR having the ability to bind a myeloid-specific polypeptide can include (e.g., can be engineered to include) nucleic acid encoding a CAR having the ability to bind a myeloid-specific polypeptide such that the CAR is expressed by the T cell. In some cases, iCARs having the ability to bind a class I MHC polypeptide (e.g., can include (a) an antigen-binding domain that binds the class I MHC polypeptide, (b) a transmembrane domain, and (c) one or more inhibitory intracellular signaling domains. For example, a T cell engineered to express an iCAR having the ability to bind a class I MHC polypeptide (e.g., can include (e.g., can be engineered to include) nucleic acid encoding an iCAR having the ability to bind a class I MHC polypeptide such that the iCAR is expressed by the T cell. This document also provides methods and materials for using T cells (e.g., CAR T cell) expressing (e.g., engineered to express) (a) one or more CARs having the ability to bind to a myeloid-specific polypeptide (e.g., a CD33 polypeptide) and (b) one or more iCARs having the ability to bind to a class I MHC polypeptide (e.g., an HLA-A polypeptide such as an HLA-A2 polypeptide). In some cases, the T cells expressing (e.g., engineered to express) (a) one or more CARs having the ability to bind to a myeloid- specific polypeptide (e.g., a CD33 polypeptide) and (b) one or more iCARs having the ability to bind to a class I MHC polypeptide (e.g., an HLA-A polypeptide such as an HLA-A2 polypeptide) can be administered (e.g., in an adoptive cell therapy) to a mammal (e.g., a human) having a myeloid neoplasm (e.g., a myeloid cancer such as AML) to treat the mammal. It should be understood that the materials and methods provided herein can be applied to any combination of class I MHC mismatched haplotypes resulting from a haploidentical bone marrow transplant. Attorney Docket No.44807-0483WO1 / P18190-01 A CAR can be any type of CAR. For example, a CAR can be a synthetic CAR that is designed to include (a) an antigen-binding domain, (b) a transmembrane domain, and (c) one or more intracellular signaling domains. For example, a CAR can be a modified TCR that is designed to include (a) an antigen-binding domain, (b) a transmembrane domain, and (c) one or more intracellular signaling domains (also referred to as a TCR CAR). In some cases, a CAR that is a modified TCR also can be designed to knock out the antigen-binding domain that is endogenous to that TCR (e.g., such that the endogenous antigen-binding domain is replaced with an exogenous antigen-binding domain such as an exogenous scFv). For example, a TCR CAR can include an antigen-binding domain that includes the constant regions of the TCR alpha and TCR beta chains and includes the variable regions of the VH and VL of an exogenous scFv. In some cases, an antigen-binding domain of a TCR CAR can be linked (directly or via a linker) to one or more of the TCR alpha, TCR beta, CD3 gamma, CD3 delta, and CD3 epsilon domains. In some cases, a VH and a VL of an antigen-binding domain of a TCR CAR can be independently linked (directly or via a linker) to separate domains the TCR. For example, a VH of an antigen-binding domain of a TCR CAR can be linked to one of a TCR alpha, TCR beta, CD3 gamma, CD3 delta, and CD3 epsilon domain, and a VL of an antigen-binding domain of a TCR CAR can be linked to one of a TCR alpha, TCR beta, CD3 gamma, CD3 delta, and CD3 epsilon domain where the VH and VL are linked to a different TCR domain. In some cases, a CAR that is a modified TCR also can include one or more additional signaling domains (e.g., one or more signaling domains that are exogenous to the TCR). For example, a TCR CAR can include one or more intracellular signaling domains (e.g., one or more signaling domains that are exogenous to the TCR such as a MyD88 intracellular signaling domain and / or a CD40 intracellular signaling domain) linked to the TCR (e.g., linked to the TCR alpha domain and / or linked to the TCR beta domain). A CAR having the ability to bind a myeloid-specific polypeptide can target any appropriate myeloid-specific polypeptide. Examples of myeloid-specific polypeptides that can be targeted by a CAR include, without limitation, CD33 polypeptides, CD123 polypeptides, FLT3 polypeptides, CLL-1 polypeptides, CD44V6 polypeptides, CD96 polypeptides, CD47 polypeptides, CD23 polypeptides, TIM3 polypeptides, CD7 Attorney Docket No.44807-0483WO1 / P18190-01 polypeptides, NKG2D polypeptides, CD117 polypeptides, CD70 polypeptides, B7-H3 polypeptides, WT1 polypeptides, PRAME polypeptides, CD34 polypeptides, CD13 polypeptides, CD11b polypeptides, CD15 polypeptides, CD14 polypeptides, CD16 polypeptides, CD24 polypeptides, CD32 polypeptides, CD38 polypeptides, LeY polypeptides, CD206 polypeptides, CD68 polypeptides, CD15 polypeptides, CSF1R polypeptides, CD64 polypeptides, CX3CR1 polypeptides, CD1A polypeptides, CD141 polypeptides, CD1C polypeptides, CD103 polypeptides, CD193 polypeptides, IL5RA polypeptides, CD163 polypeptides, ADGRE1 polypeptides, CD62L polypeptides, CXCR4 polypeptides, IDO1 polypeptides, ARG1 polypeptides, MMP9 polypeptides, ANGPT2 polypeptides, CCL2 polypeptides, CD40 polypeptides, CLEC7A polypeptides, CSF1 polypeptides, CSF1R polypeptides, CXCR2 polypeptides, CLEC12A polypeptides, CCR1 polypeptides, LILRB polypeptides, HLA-DR polypeptides, CD65 polypeptides, CD36 polypeptides, CD41 polypeptides, CD61 polypeptides, CD235a polypeptides, and MPO polypeptides. In some cases, the targeted myeloid-specific polypeptide can be a human polypeptide. For example, when a CAR targets a CD33 polypeptide, the CD33 polypeptide can be a human CD33 polypeptide. In some cases, a human CD33 polypeptide can comprising, consisting essentially of, or consisting of the amino acid set forth in SEQ ID NO:1 or SEQ ID NO:15 (see, e.g., Example 4). A CAR having the ability to bind a myeloid-specific polypeptide (e.g., a CD33 polypeptide) can include any appropriate antigen-binding domain that binds a myeloid- specific polypeptide. In some cases, an antigen-binding domain that binds a myeloid-specific polypeptide can include an antibody or a fragment thereof that targets the myeloid-specific polypeptide. Examples of antigen-binding domains include, without limitation, antigen- binding fragments (Fabs), heavy chain variable (VH) domains, light chain variable (VL) domains, single chain variable fragments (scFvs), TCR alpha chain variable domains, TCR beta chain variable domains, and single domain antibodies. For example, a CAR can include at least one set of three CDRs (e.g., a CDR1, a CDR2, and a CDR3) of an antigen-binding domain that binds a myeloid-specific polypeptide. In some cases, a CAR can include two sets of three CDRs (e.g., a VH CDR1, a VH CDR2, and a VH CDR3 and a VL CDR1, a VL Attorney Docket No.44807-0483WO1 / P18190-01 CDR2, and a VL CDR3) of an antigen-binding domain that binds a myeloid-specific polypeptide. When a CAR having the ability to bind a myeloid-specific polypeptide is a CAR having the ability to bind a CD33 polypeptide, the CAR can include (a) a heavy chain variable domain comprising (i) a VH CDR1 that comprises, consists essentially of, or consists of the amino acid sequence set forth in SEQ ID NO:2, (ii) a VH CDR2 that comprises, consists essentially of, or consists of the amino acid sequence set forth in SEQ ID NO:3, and (iii) a VH CDR3 that comprises, consists essentially of, or consists of the amino acid sequence set forth in SEQ ID NO:4, and / or (b) a light chain variable domain comprising (i) a VL CDR1 that comprises, consists essentially of, or consists of the amino acid sequence set forth in SEQ ID NO:5, (ii) a VL CDR2 that comprises, consists essentially of, or consists of the amino acid sequence set forth in SEQ ID NO:6, and (iii) a VL CDR3 that comprises, consists essentially of, or consists of the amino acid sequence set forth in SEQ ID NO:7. In some cases, a CAR having the ability to bind to a CD33 polypeptide (e.g., a human CD33 polypeptide) can include CDRs that comprise, consist essentially of, or consist of the CDR amino acid sequences set forth in Table 1. Table 1. Exemplary CDR sequences for an antigen-binding domain that can bind a CD33 polypeptide. A CDR that can be included in a CAR having the ability to bind to a CD33 polypeptide (e.g., a human CD33 polypeptide) that consists essentially of a CDR amino acid sequence set forth in any one of SEQ ID NOs:2-7 is a CDR that has zero, one, or two amino acid substitutions within the articulated sequence of the sequence identifier (e.g., any one of Attorney Docket No.44807-0483WO1 / P18190-01 SEQ ID NOs:2-7), has zero, one, two, three, four, or five amino acid residues preceding the articulated sequence of the sequence identifier (e.g., any one of SEQ ID NOs:2-7), and / or has zero, one, two, three, four, or five amino acid residues following the articulated sequence of the sequence identifier (e.g., any one of SEQ ID NOs:2-7), provided that the antigen-binding domain retains the ability to bind to a CD33 polypeptide (e.g., a human CD33 polypeptide). In some cases, a heavy chain variable domain comprising (i) a VH CDR1 that comprises the amino acid sequence set forth in SEQ ID NO:2, (ii) a VH CDR2 that comprises the amino acid sequence set forth in SEQ ID NO:3, and (iii) a VH CDR3 that comprises the amino acid sequence set forth in SEQ ID NO:4 can comprise, consist essentially of, or consist of the amino acid sequence set forth in SEQ ID NO:16. For example, a heavy chain variable domain that can be included in a CAR having the ability to bind to a CD33 polypeptide (e.g., a human CD33 polypeptide) can have at least 85% (e.g., at least 87%, at least 90%, at least 92%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) sequence identity to SEQ ID NO:16, provided that it contains (i) a VH CDR1 that comprises the amino acid sequence set forth in SEQ ID NO:2, (ii) a VH CDR2 that comprises the amino acid sequence set forth in SEQ ID NO:3, and (iii) a VH CDR3 that comprises the amino acid sequence set forth in SEQ ID NO:4. In some cases, a light chain variable domain comprising (i) a VL CDR1 that comprises the amino acid sequence set forth in SEQ ID NO:5, (ii) a VL CDR2 that comprises the amino acid sequence set forth in SEQ ID NO:6, and (iii) a VL CDR3 that comprises the amino acid sequence set forth in SEQ ID NO:7 can comprise, consist essentially of, or consist of the amino acid sequence set forth in SEQ ID NO:18. For example, a light chain variable domain that can be included in a CAR having the ability to bind to a CD33 polypeptide (e.g., a human CD33 polypeptide) can have at least 85% (e.g., at least 87%, at least 90%, at least 92%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) sequence identity to SEQ ID NO:18, provided that it contains (i) a VL CDR1 that comprises the amino acid sequence set forth in SEQ ID NO:5, (ii) a VL CDR2 that comprises the amino acid sequence set forth in SEQ ID NO:6, and (iii) a VL CDR3 that comprises the amino acid sequence set forth in SEQ ID NO:7. Attorney Docket No.44807-0483WO1 / P18190-01 When designing a single chain antibody (e.g., a scFv) having a heavy chain variable domain and a light chain variable domain, the two regions can be directly connected or can be connected using any appropriate linker sequence. For example, a heavy chain variable domain having the CDRs of SEQ ID NOs:2-4 can be directly connected to a light chain variable domain having the CDRs of SEQ ID NOs:5-7, respectively, via a linker sequence. Examples of linker sequences that can be used to connect a heavy chain variable domain and a light chain variable domain to create a scFv include, without limitation, those linkers set forth in Example 8. In some cases, an antigen-binding domain that can bind a CD33 polypeptide can be as described elsewhere (see, e.g., Kenderian et al., Leukemia, 29(8):1637-47 (2015); Sievers et al., Blood, 93(11):3678-84 (1999); U.S. Patent Application Publication No.2012 / 0251554; U.S. Patent Application Publication No.2018 / 0002397; International Patent Application Publication No. WO 2018 / 200562; International Patent Application Publication No. WO 2015 / 150526; and International Patent Application Publication No. WO 2011 / 070109). A CAR having the ability to bind a myeloid-specific polypeptide (e.g., a CD33 polypeptide) can include any appropriate transmembrane domain. Examples of transmembrane domains that can be included in a CAR include, without limitation, CD4 transmembrane domains, CD8 transmembrane domains (e.g., CD8α transmembrane domains and CD8β transmembrane domains), CD28 transmembrane domains, 4-1BB transmembrane domains, activating NK cell receptor transmembrane domains, BAFFR transmembrane domains, BLAME (SLAMF8) transmembrane domains, BTLA transmembrane domains, CD100 (SEMA4D) transmembrane domains, CD103 transmembrane domains, CD137 transmembrane domains, CD160 (BY55) transmembrane domains, CD18 transmembrane domains, CD19 transmembrane domains (e.g., CD19a transmembrane domains), CD2 transmembrane domains, CD247 transmembrane domains, CD27 transmembrane domains, CD276 (B7-H3) transmembrane domains, CD29 transmembrane domains, CD3 transmembrane domains (e.g., CD3delta, CD3 epsilon, CD3 gamma, and CD3 zeta transmembrane domains), CD30 transmembrane domains, CD40 transmembrane domains, CD49 transmembrane domains (e.g., CD49a, CD49D, and CD49f transmembrane domains), CD69 transmembrane domains, CD7 transmembrane domains, CD84 transmembrane Attorney Docket No.44807-0483WO1 / P18190-01 domains, CD96 (Tactile) transmembrane domains, CD11 transmembrane domains (e.g., CD11a, CD11b, CD11c, and CD11d transmembrane domains), CDS transmembrane domains, CEACAM1 transmembrane domains, CTLA-4 transmembrane domains, CRTAM transmembrane domains, cytokine receptor transmembrane domains, DAP-10 transmembrane domains, DNAM1 (CD226) transmembrane domains, Fc gamma receptor transmembrane domains, GADS transmembrane domains, GITR transmembrane domains, HVEM (LIGHTR) transmembrane domains, IA4 transmembrane domains, ICAM-1 transmembrane domains, Ig alpha (CD79a) transmembrane domains, IL-2R beta transmembrane domains, IL-2R gamma transmembrane domains, IL-7R alpha transmembrane domains, inducible T cell costimulator (ICOS) transmembrane domains, integrin transmembrane domains, ITGA1 transmembrane domains, ITGA4 transmembrane domains, ITGA6 transmembrane domains, ITGAD transmembrane domains, ITGAE transmembrane domains, ITGAL transmembrane domains, ITGAM transmembrane domains, ITGAX transmembrane domains, ITGB2 transmembrane domains, ITGB7 transmembrane domains, ITGB1 transmembrane domains, KIRDS2 transmembrane domains, LAT transmembrane domains, LTBR transmembrane domains, Ly9 (CD229) transmembrane domains, lymphocyte function-associated antigen-1 (LFA-1) transmembrane domains, MHC class 1 molecule transmembrane domains, NKG2C transmembrane domains, NKG2D transmembrane domains, NKp30 transmembrane domains, NKp44 transmembrane domains, NKp46 transmembrane domains, NKp80 (KLRF1) transmembrane domains, OX-40 transmembrane domains, PAG / Cbp, programmed death-1 (PD-1) transmembrane domains, PSGL1 transmembrane domains, SELPLG (CD162) transmembrane domains, SLAM transmembrane domains (e.g., SLAMF1, SLAMF4 (CD244), SLAMF6 (NTB-A), and SLAMF7 transmembrane domains), SLP-76 transmembrane domains, TNF receptor transmembrane domains (e.g., TNFR2 transmembrane domains), TNFSF14 transmembrane domains, Toll ligand receptor transmembrane domains, TRANCE / RANKL transmembrane domains, VLA1 transmembrane domains, VLA-6 transmembrane domains, TCR transmembrane domains, CD45 transmembrane domains, CD5 transmembrane domains, CD9 transmembrane domains, CD16 transmembrane domains, CD22 transmembrane domains, CD33 transmembrane domains, CD37 transmembrane domains, CD64 Attorney Docket No.44807-0483WO1 / P18190-01 transmembrane domains, CD80 transmembrane domains, CD86 transmembrane domains, CD134 transmembrane domains, CD154 transmembrane domains, and IA4 transmembrane domains. For example, a CAR that can include a transmembrane domain that comprises, consists essentially of, or consists of an amino acid sequence set forth in Example 9. In some cases, a transmembrane domain that is included in a CAR can be designed to include a transmembrane domain that comprises, consists essentially of, or consists of one of the amino acid sequences set forth in Example 9 with one, two, three, four, five, six, seven, eight, nine, or ten amino acid deletions, additions, substitutions, or combinations thereof. In some cases, a transmembrane domain that can be included in a CAR having the ability to bind a myeloid-specific polypeptide (e.g., a CD33 polypeptide) can be as described elsewhere (see, e.g., U.S. Patent Application Publication No.2024 / 0076372; and International Patent Application Publication No. WO 2022 / 192691). A CAR having the ability to bind a myeloid-specific polypeptide (e.g., a CD33 polypeptide) can include one or more of any appropriate stimulatory intracellular signaling domains. For example, a CAR can be designed to include one, two, three, four, or five stimulatory intracellular signaling domains. When a CAR includes more than one (e.g., two, three, four, or five) stimulatory intracellular signaling domains, the CAR can include any appropriate combination of stimulatory intracellular signaling domains. In some cases, a CAR can be designed to include one or more stimulatory intracellular signaling domains normally found within an immune cell (e.g., a lymphocyte such as a TIL, a T cell, a B cell, or a NK cell). Examples of stimulatory intracellular signaling domains that can be included in a CAR include, without limitation, CD3ζ intracellular signaling domains, CD28 intracellular signaling domains, 4-1BB intracellular signaling domains, CD2 intracellular signaling domains, CD4 intracellular signaling domains, OX40 intracellular signaling domains, ICOS intracellular signaling domains, BTLA intracellular signaling domains, CD27 intracellular signaling domains, CD30 intracellular signaling domains, GITR intracellular signaling domains, HVEM intracellular signaling domains, CD8 intracellular signaling domains (e.g., CD8α intracellular signaling domains and CD8β intracellular signaling domains,), activating NK cell receptor intracellular signaling domains, BAFFR intracellular signaling domains, BLAME (SLAMF8) intracellular signaling domains, CD100 (SEMA4D) intracellular Attorney Docket No.44807-0483WO1 / P18190-01 signaling domains, CD103 intracellular signaling domains, CD160 (BY55) intracellular signaling domains, CD18 intracellular signaling domains, CD19 intracellular signaling domains (e.g., CD19a intracellular signaling domains), CD247 intracellular signaling domains, CD27 intracellular signaling domains, CD276 (B7-H3) intracellular signaling domains, CD28 intracellular signaling domains, CD29 intracellular signaling domains,CD3 intracellular signaling domains (e.g., CD3delta, CD3epsilon, CD3gamma, and CD3zeta intracellular signaling domains), CD30 intracellular signaling domains, CD4 intracellular signaling domains, CD40 intracellular signaling domains, CD49 intracellular signaling domains (e.g., CD49a, CD49D, and CD49f intracellular signaling domains), CD69 intracellular signaling domains, CD7 intracellular signaling domains, CD84 intracellular signaling domains, CD96 (Tactile) intracellular signaling domains, CD11 intracellular signaling domains (e.g., CD11a, CD11b, CD11c, and CD11d intracellular signaling domains), CDS intracellular signaling domains, CEACAM1 intracellular signaling domains, CTLA-4 intracellular signaling domains, CRTAM intracellular signaling domains, cytokine receptor intracellular signaling domains, DAP-10 intracellular signaling domains, DNAM1 (CD226) intracellular signaling domains, GADS intracellular signaling domains, IA4 intracellular signaling domains, ICAM-1 intracellular signaling domains, Ig alpha (CD79a) intracellular signaling domains, IL-2Rbeta intracellular signaling domains, IL-2R gamma intracellular signaling domains, IL-7R alpha intracellular signaling domains, integrin intracellular signaling domains, ITGA4 intracellular signaling domains, ITGA6 intracellular signaling domains, ITGAD intracellular signaling domains, ITGAE intracellular signaling domains, ITGAL intracellular signaling domains, ITGAM intracellular signaling domains, ITGAX intracellular signaling domains, ITGB2 intracellular signaling domains, ITGB7 intracellular signaling domains, ITGB1 intracellular signaling domains, KIRDS2 intracellular signaling domains, LAT intracellular signaling domains, intracellular signaling domains of ligands that specifically bind with CD83, LIGHT intracellular signaling domains, LTBR intracellular signaling domains, Ly9 (CD229) intracellular signaling domains, Lyl08 intracellular signaling domains, LFA-1 intracellular signaling domains, MHC class 1 molecule intracellular signaling domains, NKG2C intracellular signaling domains, NKG2D intracellular signaling domains, NKp30 intracellular signaling domains, NKp44 intracellular Attorney Docket No.44807-0483WO1 / P18190-01 signaling domains, NKp46 intracellular signaling domains, NKp80 (KLRF1) intracellular signaling domains, PAG / Cbp intracellular signaling domains, programmed death-1 (PD-1) intracellular signaling domains, PSGL1 intracellular signaling domains, SELPLG (CD162) intracellular signaling domains, SLAM intracellular signaling domains (e.g., SLAMF1, SLAMF4 (CD244), SLAMF6 (NTB-A), and SLAMF7 intracellular signaling domains), SLP- 76 intracellular signaling domains, TNF receptor intracellular signaling domains (e.g., TNFR2 intracellular signaling domains), TNFSF14 intracellular signaling domains, TRANCE / RANKL intracellular signaling domains, VLA1 intracellular signaling domains, VLA-6 intracellular signaling domains, MyD88 intracellular signaling domains, 2B4 intracellular signaling domains, CD22 intracellular signaling domains, CD79a intracellular signaling domains, CD79b intracellular signaling domains, CRACC intracellular signaling domains, CRTAM intracellular signaling domains, DAP12 intracellular signaling domains, DR3 intracellular signaling domains, FCER1G intracellular signaling domains, FCGR1A intracellular signaling domains, FCGR2A intracellular signaling domains, FCGR2B intracellular signaling domains, FCGR3A intracellular signaling domains, FCRL1 intracellular signaling domains, FCRL2 intracellular signaling domains, FCRL3 intracellular signaling domains, FCRL4 intracellular signaling domains, FCRL5 intracellular signaling domains, FCRL6 intracellular signaling domains, ITAM intracellular signaling domains, KIR2DL1 intracellular signaling domains, KIR2DL2 intracellular signaling domains, KIR2DL3 intracellular signaling domains, KIR2DL4 intracellular signaling domains, KIR2DL5A intracellular signaling domains, KIR2DL5B intracellular signaling domains, KIR3DL1 intracellular signaling domains, KIR3DL2 intracellular signaling domains, KIR3DL3 intracellular signaling domains, LAG3 intracellular signaling domains, LILRB1 intracellular signaling domains, LILRB2 intracellular signaling domains, NKG2A intracellular signaling domains, PILRB intracellular signaling domains, SIRPa intracellular signaling domains, TIGIT intracellular signaling domains, TIM1 intracellular signaling domains, TIM3 intracellular signaling domains, TNFL6 intracellular signaling domains, TLR1 intracellular signaling domains, TLR10 intracellular signaling domains, TLR2 intracellular signaling domains, TLR3 intracellular signaling domains, TLR4 intracellular signaling domains, TLR5 intracellular signaling domains, TLR6 intracellular signaling Attorney Docket No.44807-0483WO1 / P18190-01 domains, TLR7 intracellular signaling domains, TLR8 intracellular signaling domains, and TLR9 intracellular signaling domains. In some cases, a CAR can be designed to be a first- generation CAR having a CD3ζ signaling domain. In some cases, a CAR can be designed to be a second-generation CAR having a CD28 signaling domain followed by a CD3ζ signaling domain. In some cases, a CAR can be designed to include a MyD88 intracellular signaling domain. In some cases, a CAR can be designed to include a CD40 intracellular signaling domain. In some cases when a CAR is a modified TCR (e.g., a TCR CAR), the modified TCR can be a TCR that signals through a CD3ζ signaling domain. In some cases, a CAR can be designed to include at least one stimulatory intracellular signaling domains that comprises, consists essentially of, or consists of one of the amino acid sequences set forth in Example 10. In some cases, a CAR can be designed to include at least one stimulatory intracellular signaling domain that comprises, consists essentially of, or consists of one of the amino acid sequences set forth in Example 10 with one, two, three, four, five, six, seven, eight, nine, or ten amino acid deletions, additions, substitutions, or combinations thereof, provided that that intracellular signaling domain has at least some activity to activate intracellular signaling. In some cases, a stimulatory intracellular signaling domain that can be included in a CAR having the ability to bind a myeloid-specific polypeptide (e.g., a CD33 polypeptide) can be as described elsewhere (see, e.g., International Patent Application Publication No. WO 2022 / 192691; and International Patent Application Publication No. WO 2024 / 216113). A CAR having the ability to bind a myeloid-specific polypeptide (e.g., a CD33 polypeptide) can be designed to include a hinge. Any appropriate hinge can be used to design a CAR. Examples of hinges that can be used to make a CAR include, without limitation, Ig- derived hinges (e.g., IgG4-derived hinges, IgG1-derived hinges, and IgD-derived hinges), CD8-derived hinges (e.g., CD8α-derived hinges), FcγRIIIα-derived hinges, PD-1-derived hinges, LIR-1-derived hinges, KIR2DS2-derived hinges, KIR-derived hinges, NCR-derived hinges, SLAMF-derived hinges, CD16-derived hinges, CD64-derived hinges, and LY49- derived hinges. A CAR can be designed to include a hinge of any appropriate length. For example, a CAR can be designed to include a hinge that is from about 3 to about 300 (e.g., from about 3 to about 275, from about 3 to about 250, from about 3 to about 225, from about 3 to about 200, from about 3 to about 175, from about 3 to about 150, from about 3 to about Attorney Docket No.44807-0483WO1 / P18190-01 125, from about 3 to about 100, from about 3 to about 75, from about 3 to about 50, from about 3 to about 25, from about 25 to about 300, from about 50 to about 300, from about 75 to about 300, from about 100 to about 300, from about 125 to about 300, from about 150 to about 300, from about 175 to about 300, from about 200 to about 300, from about 225 to about 300, from about 250 to about 300, from about 275 to about 300, from about 25 to about 275, from about 50 to about 250, from about 75 to about 225, from about 100 to about 200, from about 125 to about 175, from about 25 to about 75, from about 50 to about 100, from about 75 to about 125, from about 100 to about 150, from about 150 to about 200, from about 175 to about 225, from about 200 to about 250, or from about 225 to about 275) amino acid residues in length. In some cases, a linker sequence can be used as a hinge to make an antigen receptor described herein. In some cases, a CAR can be designed to include a hinge that comprises, consists essentially of, or consists of an amino acid sequence set forth in Example 8. In some cases, a CAR can be designed to include a hinge that comprises, consists essentially of, or consists of an amino acid sequence set forth in Example 8 with one, two, three, four, five, six, seven, eight, nine, or ten amino acid deletions, additions, substitutions, or combinations thereof. In some cases, a hinge that can be included in a CAR having the ability to bind a myeloid-specific polypeptide (e.g., a CD33 polypeptide) can be as described elsewhere (see, e.g., U.S. Patent Application Publication No.2020 / 0377589). An iCAR having the ability to bind a class I MHC polypeptide (e.g., an HLA-A polypeptide such as an HLA-A2 polypeptide) can target any appropriate class I MHC polypeptide. In some cases, a class I MHC polypeptide can be an HLA-A polypeptide. In some cases, a class I MHC polypeptide can be an HLA-B polypeptide. In some cases, a class I MHC polypeptide can be an HLA-C polypeptide. Examples of class I MHC polypeptides that can be targeted by an iCAR include, without limitation, HLA-A1 polypeptides, HLA-A2 polypeptides, HLA-A3 polypeptides, HLA-A23 polypeptides, HLA-A24 polypeptides, HLA- A11 polypeptides, HLA-A25 polypeptides, HLA-A26 polypeptides, HLA-A29 polypeptides, HLA-A30 polypeptides, HLA-A31 polypeptides, HLA-A32 polypeptides, HLA-A33 polypeptides, HLA-A34 polypeptides, HLA-A36 polypeptides, HLA-A43 polypeptides, HLA-A66 polypeptides, HLA-A68 polypeptides, HLA-A69 polypeptides, HLA-A74 Attorney Docket No.44807-0483WO1 / P18190-01 polypeptides, HLA-A80 polypeptides, HLA-B7 polypeptides, HLA-B8 polypeptides, HLA- B13 polypeptides, HLA-B14 polypeptides, HLA-B15 polypeptides, HLA-B18 polypeptides, HLA-B27 polypeptides, HLA-B35 polypeptides, HLA-B37 polypeptides, HLA-B38 polypeptides, HLA-B39 polypeptides, HLA-B40 polypeptides, HLA-B41 polypeptides, HLA-B42 polypeptides, HLA-B44 polypeptides, HLA-B45 polypeptides, HLA-B46 polypeptides, HLA-B47 polypeptides, HLA-B48 polypeptides, HLA-B49 polypeptides, HLA-B50 polypeptides, HLA-B51 polypeptides, HLA-B52 polypeptides, HLA-B53 polypeptides, HLA-B54 polypeptides, HLA-B55 polypeptides, HLA-B56 polypeptides, HLA-B57 polypeptides, HLA-B58 polypeptides, HLA-B59 polypeptides, HLA-B67 polypeptides, HLA-B73 polypeptides, HLA-B78 polypeptides, HLA-B79 polypeptides, HLA-B81 polypeptides, HLA-B82 polypeptides, HLA-C1 polypeptides, HLA-C2 polypeptides, HLA-C3 polypeptides, HLA-C4 polypeptides, HLA-C5 polypeptides, HLA-C6 polypeptides, HLA-C7 polypeptides, HLA-C8 polypeptides, HLA-C11 polypeptides, HLA- C12 polypeptides, HLA-C13 polypeptides, HLA-C14 polypeptides, HLA-C15 polypeptides, HLA-C16 polypeptides, HLA-C17 polypeptides, and HLA-C18 polypeptides. In some cases, an HLA-A polypeptide can comprise, consist essentially of, or consist of the amino acid set forth in SEQ ID NO:8 (see, e.g., Example 6). In cases where the methods and materials provided herein are applied a non-human mammal, an HLA polypeptide may be referred to as a major histocompatibility complex (MHC) polypeptide. An iCAR having the ability to bind a class I MHC polypeptide (e.g., an HLA-A polypeptide such as an HLA-A2 polypeptide) can include any appropriate antigen-binding domain that binds a class I MHC polypeptide. In some cases, an antigen-binding domain that binds a class I MHC polypeptide can include an antibody or a fragment thereof that targets the class I MHC polypeptide. Examples of antigen-binding domains include, without limitation, Fabs, VH domains, VL domains, scFvs, TCR alpha chain variable domains, TCR beta chain variable domains, and single domain antibodies. For example, a CAR can include at least one set of three CDRs (e.g., a CDR1, a CDR2, and a CDR3) of an antigen-binding domain that binds a class I MHC polypeptide. In some cases, a CAR can include two sets of three CDRs (e.g., a CDR1, a CDR2, and a CDR3 of a heavy chain and a CDR1, a CDR2, and a CDR3 of a light chain) of an antigen-binding domain that binds a class I MHC polypeptide. Attorney Docket No.44807-0483WO1 / P18190-01 When an iCAR having the ability to bind a class I MHC polypeptide (e.g., an HLA-A polypeptide) is a CAR having the ability to bind an HLA-A2 polypeptide, the CAR can include (a) a VH domain comprising (i) a VH CDR1 that comprises, consists essentially of, or consists of the amino acid sequence set forth in SEQ ID NO:9, (ii) a VH CDR2 that comprises, consists essentially of, or consists of the amino acid sequence set forth in SEQ ID NO:10, and (iii) a VH CDR3 that comprises, consists essentially of, or consists of the amino acid sequence set forth in SEQ ID NO:11, and / or (b) a VL domain comprising (i) a VL CDR1 that comprises, consists essentially of, or consists of the amino acid sequence set forth in SEQ ID NO:12, (ii) a VL CDR2 that comprises, consists essentially of, or consists of the amino acid sequence set forth in SEQ ID NO:13, and (iii) a VL CDR3 that comprises, consists essentially of, or consists of the amino acid sequence set forth in SEQ ID NO:14. In some cases, an iCAR having the ability to bind to an HLA-A2 polypeptide can include CDRs that comprise, consist essentially of, or consist of the CDR amino acid sequences set forth in Table 2. Table 2. Exemplary CDR sequences for an antigen-binding domain that can bind an HLA-A2 polypeptide. A CDR that can be included in an iCAR having the ability to bind an HLA-A2 polypeptide that consists essentially of a CDR amino acid sequence set forth in any one of SEQ ID NOs:9-14 is a CDR that has zero, one, or two amino acid substitutions within the articulated sequence of the sequence identifier (e.g., any one of SEQ ID NOs:9-14), has zero, one, two, three, four, or five amino acid residues preceding the articulated sequence of the sequence identifier (e.g., any one of SEQ ID NOs:9-14), and / or has zero, one, two, three, Attorney Docket No.44807-0483WO1 / P18190-01 four, or five amino acid residues following the articulated sequence of the sequence identifier (e.g., any one of SEQ ID NOs:9-14), provided that the antigen-binding domain retains the ability to bind to an HLA-A2 polypeptide. In some cases, a heavy chain variable domain comprising (i) a VH CDR1 that comprises the amino acid sequence set forth in SEQ ID NO:9, (ii) a VH CDR2 that comprises the amino acid sequence set forth in SEQ ID NO:10, and (iii) a VH CDR3 that comprises the amino acid sequence set forth in SEQ ID NO:11 can comprise, consist essentially of, or consist of the amino acid sequence set forth in SEQ ID NO:22. For example, a heavy chain variable domain that can be included in a CAR having the ability to bind to an HLA-A2 polypeptide can have at least 85% (e.g., at least 87%, at least 90%, at least 92%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) sequence identity to SEQ ID NO:22, provided that it contains (i) a VH CDR1 that comprises the amino acid sequence set forth in SEQ ID NO:9, (ii) a VH CDR2 that comprises the amino acid sequence set forth in SEQ ID NO:10, and (iii) a VH CDR3 that comprises the amino acid sequence set forth in SEQ ID NO:11. In some cases, a light chain variable domain comprising (i) a VL CDR1 that comprises the amino acid sequence set forth in SEQ ID NO:12, (ii) a VL CDR2 that comprises the amino acid sequence set forth in SEQ ID NO:13, and (iii) a VL CDR3 that comprises the amino acid sequence set forth in SEQ ID NO:14 can comprise, consist essentially of, or consist of the amino acid sequence set forth in SEQ ID NO:24. For example, a light chain variable domain that can be included in a CAR having the ability to bind to an HLA-A2 polypeptide can have at least 85% (e.g., at least 87%, at least 90%, at least 92%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) sequence identity to SEQ ID NO:24, provided that it contains (i) a VL CDR1 that comprises the amino acid sequence set forth in SEQ ID NO:12, (ii) a VL CDR2 that comprises the amino acid sequence set forth in SEQ ID NO:13, and (iii) a VL CDR3 that comprises the amino acid sequence set forth in SEQ ID NO:14. When designing a single chain antibody (e.g., a scFv) having a heavy chain variable domain and a light chain variable domain, the two regions can be directly connected or can be connected using any appropriate linker sequence. For example, a heavy chain variable Attorney Docket No.44807-0483WO1 / P18190-01 domain having the CDRs of SEQ ID NOs:9-11 can be directly connected to a light chain variable domain having the CDRs of SEQ ID NOs:12-14, respectively, via a linker sequence. Examples of linker sequences that can be used to connect a heavy chain variable domain and a light chain variable domain to create a scFv include, without limitation, those linkers set forth in Example 8. In some cases, an antigen-binding domain that can bind an HLA-A2 polypeptide can be as described elsewhere (see, e.g., Parham et al., Hum. Immunol., 3(4):277-99 (1981); Hwang et al., Proc. Natl. Acad. Sci. USA, 118(12):e2022410118 (2021); Muller et al., Front. Immunol., 12:686439 (2021); and U.S. Patent Application Publication No.2022 / 0289818). An iCAR having the ability to bind a class I MHC polypeptide (e.g., an HLA-A polypeptide such as an HLA-A2 polypeptide) can include any appropriate transmembrane domain. In some cases, a transmembrane domain that can be used to design an iCAR can be a transmembrane domain derived from an inhibitory receptor. Examples of transmembrane domains that can be included in an iCAR include, without limitation, CD4 transmembrane domains, CD8 transmembrane domains (e.g., CD8α transmembrane domains and CD8β transmembrane domains), CD28 transmembrane domains, LIR-1 transmembrane domains, 4- 1BB transmembrane domains, activating NK cell receptor transmembrane domains, BAFFR transmembrane domains, BLAME (SLAMF8) transmembrane domains, BTLA transmembrane domains, CD100 (SEMA4D) transmembrane domains, CD103 transmembrane domains, CD137 transmembrane domains, CD160 (BY55) transmembrane domains, CD18 transmembrane domains, CD19 transmembrane domains (e.g., CD19a transmembrane domains), CD2 transmembrane domains, CD247 transmembrane domains, CD27 transmembrane domains, CD276 (B7-H3) transmembrane domains, CD29 transmembrane domains, CD3 transmembrane domains (e.g., CD3delta, CD3 epsilon, CD3 gamma, and CD3 zeta transmembrane domains), CD30 transmembrane domains, CD40 transmembrane domains, CD49 transmembrane domains (e.g., CD49a, CD49D, and CD49f transmembrane domains), CD69 transmembrane domains, CD7 transmembrane domains, CD84 transmembrane domains, CD96 (Tactile) transmembrane domains, CD11 transmembrane domains (e.g., CD11a, CD11b, CD11c, and CD11d transmembrane domains), CDS transmembrane domains, CEACAM1 transmembrane domains, CTLA-4 Attorney Docket No.44807-0483WO1 / P18190-01 transmembrane domains, CRTAM transmembrane domains, cytokine receptor transmembrane domains, DAP-10 transmembrane domains, DNAM1 (CD226) transmembrane domains, Fc gamma receptor transmembrane domains, GADS transmembrane domains, GITR transmembrane domains, HVEM (LIGHTR) transmembrane domains, IA4 transmembrane domains, ICAM-1 transmembrane domains, Ig alpha (CD79a) transmembrane domains, IL-2R beta transmembrane domains, IL-2R gamma transmembrane domains, IL-7R alpha transmembrane domains, inducible T cell costimulator (ICOS) transmembrane domains, integrin transmembrane domains, ITGA1 transmembrane domains, ITGA4 transmembrane domains, ITGA6 transmembrane domains, ITGAD transmembrane domains, ITGAE transmembrane domains, ITGAL transmembrane domains, ITGAM transmembrane domains, ITGAX transmembrane domains, ITGB2 transmembrane domains, ITGB7 transmembrane domains, ITGB1 transmembrane domains, KIRDS2 transmembrane domains, LAT transmembrane domains, LTBR transmembrane domains, Ly9 (CD229) transmembrane domains, lymphocyte function-associated antigen-1 (LFA-1) transmembrane domains, MHC class 1 molecule transmembrane domains, NKG2C transmembrane domains, NKG2D transmembrane domains, NKp30 transmembrane domains, NKp44 transmembrane domains, NKp46 transmembrane domains, NKp80 (KLRF1) transmembrane domains, OX- 40 transmembrane domains, PAG / Cbp, programmed death-1 (PD-1) transmembrane domains, PSGL1 transmembrane domains, SELPLG (CD162) transmembrane domains, SLAM transmembrane domains (e.g., SLAMF1, SLAMF4 (CD244), SLAMF6 (NTB-A), and SLAMF7 transmembrane domains), SLP-76 transmembrane domains, TNF receptor transmembrane domains (e.g., TNFR2 transmembrane domains), TNFSF14 transmembrane domains, Toll ligand receptor transmembrane domains, TRANCE / RANKL transmembrane domains, VLA1 transmembrane domains, VLA-6 transmembrane domains, TCR transmembrane domains, CD45 transmembrane domains, CD5 transmembrane domains, CD9 transmembrane domains, CD16 transmembrane domains, CD22 transmembrane domains, CD33 transmembrane domains, CD37 transmembrane domains, CD64 transmembrane domains, CD80 transmembrane domains, CD86 transmembrane domains, CD134 transmembrane domains, CD154 transmembrane domains, and IA4 transmembrane domains. For example, an iCAR that can include a transmembrane domain that comprises, Attorney Docket No.44807-0483WO1 / P18190-01 consists essentially of, or consists of an amino acid sequence set forth in Example 9. In some cases, a transmembrane domain that is included in an iCAR can be designed to include a transmembrane domain that comprises, consists essentially of, or consists of one of the amino acid sequences set forth in Example 9 with one, two, three, four, five, six, seven, eight, nine, or ten amino acid deletions, additions, substitutions, or combinations thereof. In some cases, a transmembrane domain that can be included in iCAR having the ability to bind a class I MHC polypeptide (e.g., an HLA-A polypeptide such as an HLA-A2 polypeptide) can be as described elsewhere (see, e.g., U.S. Patent Application Publication No.2024 / 0076372; and International Patent Application Publication No. WO 2022 / 192691). An iCAR having the ability to bind a class I MHC polypeptide (e.g., an HLA-A polypeptide such as an HLA-A2 polypeptide) can include any appropriate one or more inhibitory intracellular signaling domains. In some cases, an intracellular signaling domain that can be used to design an iCAR can be an intracellular signaling domain derived from an inhibitory receptor. In some cases, an intracellular signaling domain that can be used to design an iCAR can include one or more immunoreceptor tyrosine-based inhibitory motifs (ITIMs). For example, an iCAR can be designed to include one, two, three, four, or five inhibitory intracellular signaling domains. When an iCAR includes more than one (e.g., two, three, four, or five) inhibitory intracellular signaling domains, the iCAR can include any appropriate combination of inhibitory intracellular signaling domains. In some cases, an iCAR can be designed to include one or more inhibitory intracellular signaling domains normally found within an inhibitory immunoreceptor. Examples of inhibitory intracellular signaling domains that can be included in an iCAR include, without limitation, PD-1 intracellular signaling domains, LIR-1 (LILRB1) intracellular signaling domains, CTLA-4 intracellular signaling domains, BTLA intracellular signaling domains, LAG3 intracellular signaling domains, PD-L1 intracellular signaling domains, HAVCR2 (TIM3) intracellular signaling domains, KIR2DL2 intracellular signaling domains, TIGIT intracellular signaling domains, CEACAM1 intracellular signaling domains, CEACAM3 intracellular signaling domains, CEACAM5 intracellular signaling domains, CSF1R intracellular signaling domains, CDS intracellular signaling domains, CD96 intracellular signaling domains, CD22 intracellular signaling domains, LAIR intracellular signaling domains, 2B4 intracellular Attorney Docket No.44807-0483WO1 / P18190-01 signaling domains, CD3-zeta intracellular signaling domains, VISTA intracellular signaling domains, CD160 intracellular signaling domains, TGF beta intracellular signaling domains, SIGLEC intracellular signaling domains, and IgSF intracellular signaling domains. In some cases, an iCAR can be designed to include at least one inhibitory intracellular signaling domains that comprises, consists essentially of, or consists of one of the amino acid sequences set forth in Example 11. In some cases, an iCAR can be designed to include at least one inhibitory intracellular signaling domains that comprises, consists essentially of, or consists of one of the amino acid sequences set forth in Example 11 with one, two, three, four, five, six, seven, eight, nine, or ten amino acid deletions, additions, substitutions, or combinations thereof, provided that that intracellular signaling domain has at least some ability to inhibit intracellular signaling. In some cases, iCAR having the ability to bind a class I MHC polypeptide (e.g., an HLA-A polypeptide such as an HLA-A2 polypeptide) can be designed to include a transmembrane domain and an intracellular signaling domain that are derived from the same inhibitory receptor. In some cases, an inhibitory intracellular signaling domain that can be included in iCAR having the ability to bind a class I MHC polypeptide (e.g., an HLA-A polypeptide such as an HLA-A2 polypeptide) can be as described elsewhere (see, e.g., U.S. Patent Application Publication No.2024 / 0076372; and International Patent Application Publication No. WO 2022 / 192691). An iCAR having the ability to bind a class I MHC polypeptide (e.g., an HLA-A polypeptide such as an HLA-A2 polypeptide) can be designed to include a hinge. Any appropriate hinge can be used to design an iCAR. In some cases, a hinge that can be used to design an iCAR can be a hinge derived from an inhibitory receptor. Examples of hinges that can be used to make an iCAR include, without limitation, Ig-derived hinges (e.g., IgG4- derived hinges, IgG1-derived hinges, and IgD-derived hinges), CD8-derived hinges (e.g., CD8α-derived hinges), FcγRIIIα-derived hinges, PD-1-derived hinges, LIR-1-derived hinges, KIR2DS2-derived hinges, KIR-derived hinges, NCR-derived hinges, SLAMF-derived hinges, CD16-derived hinges, CD64-derived hinges, and LY49-derived hinges. An iCAR can be designed to include a hinge of any appropriate length. For example, a CAR can be Attorney Docket No.44807-0483WO1 / P18190-01 designed to include a hinge that is from about 3 to about 300 (e.g., from about 3 to about 275, from about 3 to about 250, from about 3 to about 225, from about 3 to about 200, from about 3 to about 175, from about 3 to about 150, from about 3 to about 125, from about 3 to about 100, from about 3 to about 75, from about 3 to about 50, from about 3 to about 25, from about 25 to about 300, from about 50 to about 300, from about 75 to about 300, from about 100 to about 300, from about 125 to about 300, from about 150 to about 300, from about 175 to about 300, from about 200 to about 300, from about 225 to about 300, from about 250 to about 300, from about 275 to about 300, from about 25 to about 275, from about 50 to about 250, from about 75 to about 225, from about 100 to about 200, from about 125 to about 175, from about 25 to about 75, from about 50 to about 100, from about 75 to about 125, from about 100 to about 150, from about 150 to about 200, from about 175 to about 225, from about 200 to about 250, or from about 225 to about 275) amino acid residues in length. In some cases, a linker sequence can be used as a hinge to make an antigen receptor described herein. In some cases, an iCAR can be designed to include a hinge that comprises, consists essentially of, or consists of an amino acid sequence set forth in Example 8. In some cases, an iCAR can be designed to include a hinge that comprises, consists essentially of, or consists of an amino acid sequence set forth in Example 8 with one, two, three, four, five, six, seven, eight, nine, or ten amino acid deletions, additions, substitutions, or combinations thereof. In some cases, a hinge that can be included in an iCAR having the ability to bind a class I MHC polypeptide (e.g., an HLA-A polypeptide such as an HLA-A2 polypeptide) can be as described elsewhere (see, e.g., U.S. Patent Application Publication No.2020 / 0377589). Also provided herein are T cells (e.g., CAR T) expressing (e.g., engineered to express) (a) one or more CARs having the ability to bind to a myeloid-specific polypeptide (e.g., a CD33 polypeptide) and (b) one or more iCARs having the ability to bind to a class I MHC polypeptide (e.g., an HLA-A polypeptide such as an HLA-A2 polypeptide). Examples of T cells that can be engineered to express (a) one or more CARs having the ability to bind to a myeloid-specific polypeptide (e.g., a CD33 polypeptide) and (b) one or more iCARs having the ability to bind to a class I MHC polypeptide (e.g., an HLA-A polypeptide such as an HLA-A2 polypeptide) as described herein include, without limitation, peripheral T cells, Attorney Docket No.44807-0483WO1 / P18190-01 pluripotent stem cell-derived T cells such as induced pluripotent stem cell-derived T cells, CD34+ hematopoietic stem cell-derived T cells, T cells obtained from bone marrow, T cells obtained from lymph node tissue, T cells obtained from cord blood, T cells obtained from thymus tissue, T cells obtained from a site of infection, T cells obtained from ascites, T cells obtained from pleural effusion, T cells obtained from splenic tissue, and T cells obtained from tumors. In some cases, one or more T cells designed to express (a) one or more CARs having the ability to bind to a myeloid-specific polypeptide (e.g., a CD33 polypeptide) and (b) one or more iCARs having the ability to bind to a class I MHC polypeptide (e.g., an HLA-A polypeptide such as an HLA-A2 polypeptide) can be allogenic T cells (e.g., T cells that were obtained from a donor mammal). For example, T cells can be obtained from the same mammal that served as the donor for the bone marrow transplant material and can be designed to express (a) one or more CARs having the ability to bind to a myeloid-specific polypeptide (e.g., a CD33 polypeptide) and (b) one or more iCARs having the ability to bind to a class I MHC polypeptide (e.g., an HLA-A polypeptide such as an HLA-A2 polypeptide) as described herein. In some cases, one or more T cells designed to express (a) one or more CARs having the ability to bind to a myeloid-specific polypeptide (e.g., a CD33 polypeptide) and (b) one or more iCARs having the ability to bind to a class I MHC polypeptide (e.g., an HLA-A polypeptide such as an HLA-A2 polypeptide) can be autologous T cells (e.g., T cells that were obtained from a mammal (e.g., a mammal having a myeloid neoplasm such as a myeloid cancer) that is to be treated with those T cells. For example, T cells can be obtained from a mammal to be treated with the materials and methods described herein and can be designed to express (a) one or more CARs having the ability to bind to a myeloid-specific polypeptide (e.g., a CD33 polypeptide) and (b) one or more iCARs having the ability to bind to a class I MHC polypeptide (e.g., an HLA-A polypeptide such as an HLA-A2 polypeptide) as described herein. In some cases, a T cell (e.g., a CAR T cell) provided herein (e.g., a T cell engineered to express (a) one or more CARs having the ability to bind to a myeloid-specific polypeptide (e.g., a CD33 polypeptide) and (b) one or more iCARs having the ability to bind to a class I MHC polypeptide (e.g., an HLA-A polypeptide such as an HLA-A2 polypeptide)) can have Attorney Docket No.44807-0483WO1 / P18190-01 reduced toxicity (e.g., as compared to a T cell that is not engineered to express (a) one or more CARs having the ability to bind to a myeloid-specific polypeptide (e.g., a CD33 polypeptide) and (b) one or more iCARs having the ability to bind to a class I MHC polypeptide (e.g., an HLA-A polypeptide such as an HLA-A2 polypeptide) as described herein). For example, a T cell provided herein can have reduced toxicity as compared to a T cell that is engineered to express one or more CARs having the ability to bind to a myeloid- specific polypeptide (e.g., a CD33 polypeptide) but is not engineered to express one or more iCARs having the ability to bind to a class I MHC polypeptide (e.g., an HLA-A polypeptide such as an HLA-A2 polypeptide). Any appropriate method can be used to express one or more CARs having the ability to bind to a myeloid-specific polypeptide (e.g., a CD33 polypeptide) and / or one or more iCARs having the ability to bind to a class I MHC polypeptide (e.g., an HLA-A polypeptide such as an HLA-A2 polypeptide) on a T cell. In some cases, exogenous nucleic acid encoding one or more CARs having the ability to bind to a myeloid-specific polypeptide and / or nucleic acid encoding one or more iCARs having the ability to bind to a class I MHC polypeptide (e.g., an HLA-A polypeptide such as an HLA-A2 polypeptide) can be introduced into a T cell such that the T cell expresses one or more CARs (e.g., TCR CARs) having the ability to bind to a myeloid-specific polypeptide (e.g., a CD33 polypeptide) and / or one or more iCARs having the ability to bind to a class I MHC polypeptide (e.g., an HLA-A polypeptide such as an HLA-A2 polypeptide). For example, nucleic acid encoding one or more CARs having the ability to bind to a myeloid-specific polypeptide and / or nucleic acid encoding one or more iCARs having the ability to bind to a class I MHC polypeptide (e.g., an HLA-A polypeptide such as an HLA-A2 polypeptide) can be introduced into a T cell. In some cases, nucleic acid encoding one or more CARs having the ability to bind to a myeloid- specific polypeptide and / or nucleic acid encoding one or more iCARs having the ability to bind to a class I MHC polypeptide (e.g., an HLA-A polypeptide such as an HLA-A2 polypeptide) can be introduced into a T cell by transduction (e.g., viral transduction using a viral vector such as a lentiviral vector) or transfection. In some cases, nucleic acid encoding one or more CARs having the ability to bind to a myeloid-specific polypeptide and / or nucleic acid encoding one or more iCARs having the ability to bind to a class I MHC polypeptide Attorney Docket No.44807-0483WO1 / P18190-01 (e.g., an HLA-A polypeptide such as an HLA-A2 polypeptide) can be introduced ex vivo into one or more T cells. For example, ex vivo engineering of T cells can include transducing isolated T cells with a lentiviral vector containing nucleic acid encoding one or more CARs having the ability to bind to a myeloid-specific polypeptide and / or nucleic acid encoding one or more iCARs having the ability to bind to a class I MHC polypeptide (e.g., an HLA-A polypeptide such as an HLA-A2 polypeptide). In another example, ex vivo engineering of T cells can include transfecting isolated T cells with a CRISPR knock-in system (e.g., a CRISPR knock-in system targeting a TCR alpha chain constant locus within the isolated T cells) including a homology-directed repair template including nucleic acid encoding one or more CARs having the ability to bind to a myeloid-specific polypeptide and / or nucleic acid encoding one or more iCARs having the ability to bind to a class I MHC polypeptide (e.g., an HLA-A polypeptide such as an HLA-A2 polypeptide). In cases where T cells are engineered ex vivo to express one or more CARs having the ability to bind to a myeloid-specific polypeptide and one or more iCARs having the ability to bind to a class I MHC polypeptide (e.g., an HLA-A polypeptide such as an HLA-A2 polypeptide), the T cells can be obtained from any appropriate source (e.g., a mammal such as the mammal to be treated or a donor mammal, or a cell line). In some cases, nucleic acid encoding one or more CARs having the ability to bind to a myeloid-specific polypeptide and / or nucleic acid encoding one or more iCARs having the ability to bind to a class I MHC polypeptide (e.g., an HLA-A polypeptide such as an HLA-A2 polypeptide) can be introduced in vivo into one or more T cells. For example, in vivo engineering of T cells can include administering an adeno-associated viral (AAV) vector containing nucleic acid encoding one or more CARs having the ability to bind to a myeloid-specific polypeptide and / or nucleic acid encoding one or more iCARs having the ability to bind to a class I MHC polypeptide (e.g., an HLA-A polypeptide such as an HLA-A2 polypeptide) to a mammal (e.g., a human) under conditions where the AAV vector can transduce a T cell in vivo such that the transduced T cell express the CAR(s). In some cases, a T cell can be designed to express one or more CARs having the ability to bind to a myeloid-specific polypeptide (e.g., a CD33 polypeptide) and / or one or more iCARs having the ability to bind to a class I MHC polypeptide (e.g., an HLA-A Attorney Docket No.44807-0483WO1 / P18190-01 polypeptide such as an HLA-A2 polypeptide) as described in any one of Example 1, Example 2, and / or Example 3. In some cases, nucleic acid encoding a TCR that is endogenous to a T cell can be edited to include nucleic acid encoding an antigen-binding domain having the ability to bind to a myeloid-specific polypeptide (e.g., a CD33 polypeptide) and / or an antigen-binding domain having the ability to bind to a class I MHC polypeptide (e.g., an HLA-A polypeptide such as an HLA-A2 polypeptide) (and, optionally, to knock-out the nucleic acid encoding the antigen-binding domain endogenous to that TCR) such that the T cell expresses one or more CARs (e.g., TCR CARs) having the ability to bind to a myeloid-specific polypeptide (e.g., a CD33 polypeptide) and / or one or more iCARs having the ability to bind to a class I MHC polypeptide (e.g., an HLA-A polypeptide such as an HLA-A2 polypeptide). For example, gene editing components (e.g., CRISPR constructs) designed to replace (e.g., via homology- directed repair) endogenous nucleic acid encoding an antigen-binding domain of a TCR with nucleic acid encoding an antigen-binding domain having the ability to bind to a myeloid- specific polypeptide and / or nucleic acid encoding an antigen-binding domain having the ability to bind to an a class I MHC polypeptide (e.g., HLA-A polypeptide such as an HLA- A2 polypeptide) can be introduced into a T cell. In some cases, gene editing components (e.g., CRISPR constructs) can be introduced into a T cell by transduction (e.g., viral transduction using a viral vector such as a lentiviral vector) or transfection. In some cases, gene editing components (e.g., CRISPR constructs) can be introduced ex vivo into one or more T cells. For example, ex vivo engineering of T cells can include transducing isolated T cells with a lentiviral vector containing gene editing components (e.g., CRISPR constructs). In cases where T cells are engineered ex vivo to express one or more CARs having the ability to bind to a myeloid-specific polypeptide and one or more iCARs having the ability to bind to a class I MHC polypeptide (e.g., an HLA-A polypeptide such as an HLA-A2 polypeptide), the T cells can be obtained from any appropriate source (e.g., a mammal such as the mammal to be treated or a donor mammal, or a cell line). In some cases, endogenous nucleic acid encoding a TCR can be edited to include nucleic acid encoding an antigen-binding domain having the ability to bind to a myeloid-specific polypeptide (e.g., a CD33 polypeptide) and / or an antigen-binding domain having the ability to bind to a class I MHC polypeptide (e.g., an Attorney Docket No.44807-0483WO1 / P18190-01 HLA-A polypeptide such as an HLA-A2 polypeptide) (and, optionally, to knock-out the nucleic acid encoding the antigen-binding domain endogenous to that TCR) as described in in any one of Example 1, Example 2, and / or Example 3. This document also provides methods and materials involved in treating myeloid neoplasms (e.g., myeloid cancers such as AML). For example, one or more T cells (e.g., CAR T cells) provided herein (e.g., one or more T cells expressing (e.g., engineered to express) (a) one or more CARs having the ability to bind to a myeloid-specific polypeptide (e.g., a CD33 polypeptide) and (b) one or more iCARs having the ability to bind to a class I MHC polypeptide (e.g., an HLA-A polypeptide such as an HLA-A2 polypeptide)) can be administered (e.g., in an adoptive cell therapy such as a CAR T cell therapy) to a mammal (e.g., a human) having a myeloid neoplasm (e.g., a myeloid cancer such as AML) to treat the mammal. Any appropriate mammal (e.g., a human) having a myeloid neoplasm (e.g., a myeloid cancer such as AML) can be treated as described herein (e.g., by administering one or more T cells (e.g., CAR T cells) provided herein such as one or more T cells expressing (e.g., engineered to express) (a) one or more CARs having the ability to bind to a myeloid-specific polypeptide (e.g., a CD33 polypeptide) and (b) one or more iCARs having the ability to bind to a class I MHC polypeptide (e.g., an HLA-A polypeptide such as an HLA-A2 polypeptide)). Examples of mammals that can be treated as described herein include, without limitation, humans, primates (such as monkeys), dogs, cats, horses, cows, pigs, sheep, mice, and rats. In some cases, a human having a myeloid neoplasm can be treated with one or more T cells (e.g., CAR T cells) provided herein (e.g., one or more T cells expressing (e.g., engineered to express) (a) one or more CARs having the ability to bind to a myeloid-specific polypeptide (e.g., a CD33 polypeptide) and (b) one or more iCARs having the ability to bind to a class I MHC polypeptide (e.g., an HLA-A polypeptide such as an HLA-A2 polypeptide)). For example, a human having a myeloid neoplasm (e.g., a myeloid cancer such as AML) and having received a haploidentical bone marrow transplant can be administered one or more T cells (e.g., CAR T cells) provided herein (e.g., one or more T cells expressing (e.g., engineered to express) (a) one or more CARs having the ability to bind to a myeloid-specific polypeptide (e.g., a CD33 polypeptide) and (b) one or more iCARs Attorney Docket No.44807-0483WO1 / P18190-01 having the ability to bind to a class I MHC polypeptide (e.g., an HLA-A polypeptide such as an HLA-A2 polypeptide)) in an adoptive T cell therapy such as a CAR T cell therapy using the methods and materials described herein. When treating a mammal (e.g., a human) having a myeloid neoplasm as described herein, the myeloid neoplasm can be any type of myeloid neoplasm. In some cases, a myeloid neoplasm can be a myeloid cancer. When a myeloid neoplasm is a myeloid cancer, the myeloid cancer can be any type of myeloid cancer. In some cases, a myeloid cancer treated as described herein can include one or more solid tumors. In some cases, a myeloid cancer treated as described herein can be a primary cancer. In some cases, a myeloid cancer treated as described herein can be a metastatic cancer. In some cases, a myeloid cancer treated as described herein can be a refractory cancer. In some cases, a myeloid cancer treated as described herein can be a relapsed cancer. In some cases, a myeloid neoplasm treated as described herein can express a CD33 polypeptide. Examples of myeloid neoplasms that can be treated as described herein include, without limitation, AMLs, myeloid sarcomas, chronic myelogenous leukemias (CMLs), chronic myelomonocytic leukemias (CMMLs), acute promyelocytic leukemias (APLs), juvenile myelomonocytic leukemias (JMMLs), myelodysplastic syndromes, and myeloproliferative neoplasms (e.g., polycythemia vera, essential thrombocythemia, primary myelofibrosis, chronic neutrophilic leukemia, and chronic eosinophilic leukemia). In some cases, the methods and materials described herein could also be used to treat one or more diseases that are not a myeloid neoplasm but can be treated with a bone marrow transplant. Examples of diseases that can be treated with a bone marrow transplant (other than myeloid neoplasms) and could be treated using the methods and materials described herein include, without limitation, follicular lymphomas, multiple myelomas, acute lymphoblastic leukemias (ALLs), chronic lymphocytic leukemias (CLLs), diffuse large B cell lymphomas (DLBCLs), peripheral T cell lymphomas (PTCLs), sickle cell anemias, beta thalassemias, Diamond-Blackfan anemias, idiopathic severe aplastic anemias, paroxysmal nocturnal hemoglobinurias, pure red cell aplasias, Fanconi anemias, amegakaryocytoses, and congenital thrombocytopenias. In such cases, a mammal can be treated with one or more T cells (e.g., CAR T cells) expressing (e.g., engineered to express) (a) one or more CARs Attorney Docket No.44807-0483WO1 / P18190-01 having the ability to bind to a polypeptide expressed on the surface of a recipient-derived diseased cell and (b) one or more iCARs having the ability to bind to a class I MHC polypeptide (e.g., an HLA-A polypeptide such as an HLA-A2 polypeptide) expressed on the surface of a donor derived healthy cell. In some cases, the methods described herein can include identifying a mammal (e.g., a human) as having a myeloid neoplasm (e.g., a myeloid cancer such as AML). Any appropriate method can be used to identify a mammal having a myeloid neoplasm. For example, imaging techniques and biopsy techniques can be used to identify mammals (e.g., humans) having a myeloid neoplasm. In some cases, the methods described herein can include identifying a mammal (e.g., a human) as having neoplastic myeloid cells that express a particular myeloid-specific polypeptide (e.g., a CD33 polypeptide). Any appropriate method can be used to identify a neoplastic myeloid cell as expressing a particular antigen. For example, immunodiagnostic assays (e.g., flow cytometry, western blotting, immunoprecipitation, enzyme-linked immunosorbent assays (ELISAs), immunohistochemistry assays, and immunofluorescent microscopy) and / or mass spectrometry can be used to identify a neoplastic myeloid cell as expressing a particular myeloid-specific polypeptide. Any appropriate amount (e.g., number) of one or more T cells (e.g., CAR T cells) provided herein (e.g., one or more T cells expressing (e.g., engineered to express) (a) one or more CARs having the ability to bind to a myeloid-specific polypeptide (e.g., a CD33 polypeptide) and (b) one or more iCARs having the ability to bind to a class I MHC polypeptide (e.g., an HLA-A polypeptide such as an HLA-A2 polypeptide)) can be administered (e.g., in an adoptive cell therapy such as a CAR T cell therapy) to a mammal (e.g., a human) having a myeloid neoplasm (e.g., a myeloid cancer such as AML). In some cases, from about 0.5 x 106cells per kg body weight of the mammal (cells / kg) to about 2 x 106cells / kg (e.g., from about 0.5 x 106cells / kg to about 1.5 x 106cells / kg, from about 0.5 x 106cells / kg to about 1 x 106cells / kg, from about 1 x 106cells / kg to about 2 x 106cells / kg, from about 1.5 x 106cells / kg to about 2 x 106cells / kg, or from about 1 x 106cells / kg to about 1.5 x 106cells / kg) of one or more T cells (e.g., CAR T cells) provided herein can be administered to a mammal having a myeloid neoplasm to treat the mammal. Attorney Docket No.44807-0483WO1 / P18190-01 A mammal (e.g., a human) having a myeloid neoplasm (e.g., a myeloid cancer such as AML) can be administered one or more T cells (e.g., CAR T cells) provided herein (e.g., one or more T cells expressing (e.g., engineered to express) (a) one or more CARs having the ability to bind to a myeloid-specific polypeptide (e.g., a CD33 polypeptide) and (b) one or more iCARs having the ability to bind to a class I MHC polypeptide (e.g., an HLA-A polypeptide such as an HLA-A2 polypeptide)) using any appropriate method. For example, one or more T cells provided herein can be used in an adoptive T cell therapy (e.g., a CAR T cell therapy) to treat a mammal having a myeloid neoplasm. In some cases, materials and methods provided herein can be effective to treat a mammal having a myeloid neoplasm (e.g., a myeloid cancer such as AML). For example, one or more T cells (e.g., CAR T cells) provided herein (e.g., one or more T cells expressing (e.g., engineered to express) (a) one or more CARs having the ability to bind to a myeloid- specific polypeptide (e.g., a CD33 polypeptide) and (b) one or more iCARs having the ability to bind to a class I MHC polypeptide (e.g., an HLA-A polypeptide such as an HLA-A2 polypeptide)) can be administered to a mammal (e.g., a human) having a myeloid cancer and in need of treatment thereof to reduce the size of a cancer present within the mammal. For example, the materials and methods described herein can be used to reduce the number of cancer cells present within a mammal having myeloid cancer by, for example, 10, 20, 30, 40, 50, 60, 70, 80, 90, 95, or more percent. For example, the materials and methods described herein can be used to reduce the size (e.g., volume) of one or more tumors present within a mammal having myeloid cancer by, for example, 10, 20, 30, 40, 50, 60, 70, 80, 90, 95, or more percent. In some cases, materials and methods provided herein can be effective to improve survival of a mammal having a myeloid neoplasm (e.g., a myeloid cancer such as AML). For example, one or more T cells (e.g., CAR T cells) provided herein (e.g., one or more T cells expressing (e.g., engineered to express) (a) one or more CARs having the ability to bind to a myeloid-specific polypeptide (e.g., a CD33 polypeptide) and (b) one or more iCARs having the ability to bind to a class I MHC polypeptide (e.g., an HLA-A polypeptide such as an HLA-A2 polypeptide)) can be administered to a mammal (e.g., a human) having myeloid cancer and in need of treatment thereof to improve survival (e.g., overall survival, disease- Attorney Docket No.44807-0483WO1 / P18190-01 free survival and / or event free survival) of the mammal. For example, disease-free survival (e.g., relapse-free survival) can be improved using the materials and methods described herein. In some cases, the materials and methods described herein can be used to improve the survival of a mammal having myeloid cancer by, for example, 10, 20, 30, 40, 50, 60, 70, 80, 90, 95, or more percent. In some cases, materials and methods provided herein can be effective to increase the number of tumor-infiltrating lymphocytes (e.g., T cells present in within the tumor microenvironment of a cancer) within the mammal. For example, one or more T cells (e.g., CAR T cells) provided herein (e.g., one or more T cells expressing (e.g., engineered to express) (a) one or more CARs having the ability to bind to a myeloid-specific polypeptide (e.g., a CD33 polypeptide) and (b) one or more iCARs having the ability to bind to a class I MHC polypeptide (e.g., an HLA-A polypeptide such as an HLA-A2 polypeptide)) can be administered to a mammal (e.g., a human) having a myeloid neoplasm (e.g., a myeloid cancer such as AML) and in need of treatment thereof and can infiltrate the tumor to increase the number of tumor-infiltrating lymphocytes within the mammal. For example, the materials and methods described herein can be used to increase the number of tumor-infiltrating lymphocytes within a mammal having myeloid cancer by, for example, 10, 20, 30, 40, 50, 60, 70, 80, 90, 95, or more percent. In some cases, one or more T cells (e.g., CAR T cells) provided herein (e.g., one or more T cells expressing (e.g., engineered to express) (a) one or more CARs having the ability to bind to a myeloid-specific polypeptide (e.g., a CD33 polypeptide) and (b) one or more iCARs having the ability to bind to a class I MHC polypeptide (e.g., an HLA-A polypeptide such as an HLA-A2 polypeptide)) can be formulated into a composition (e.g., a pharmaceutically acceptable composition) for administration to a mammal having a myeloid neoplasm (e.g., a myeloid cancer such as AML). For example, one or more T cells (e.g., CAR T cells) provided herein can be formulated together with one or more pharmaceutically acceptable carriers (additives), excipients, and / or diluents. In some cases, a pharmaceutically acceptable carrier, excipient, or diluent can be a naturally occurring pharmaceutically acceptable carrier, excipient, or diluent. In some cases, a pharmaceutically acceptable carrier, excipient, or diluent can be a non-naturally occurring (e.g., an artificial or synthetic) Attorney Docket No.44807-0483WO1 / P18190-01 pharmaceutically acceptable carrier, excipient, or diluent. Examples of pharmaceutically acceptable carriers, excipients, and diluents that can be used in a composition described herein include, without limitation, serum proteins (e.g., human serum albumin), water, and salts or electrolytes (e.g., phosphate salts, saline, protamine sulfate, and DMSO). A composition containing one or more T cells (e.g., CAR T cells) provided herein (e.g., one or more T cells expressing (e.g., engineered to express) (a) one or more CARs having the ability to bind to a myeloid-specific polypeptide (e.g., a CD33 polypeptide) and (b) one or more iCARs having the ability to bind to a class I MHC polypeptide (e.g., an HLA-A polypeptide such as an HLA-A2 polypeptide)) can be designed for parenteral (including subcutaneous, intramuscular, intravenous, and intradermal) or intratumoral administration. Compositions suitable for parenteral administration include aqueous and non- aqueous sterile injection solutions that can contain anti-oxidants, buffers, bacteriostats, and solutes that render the formulation isotonic with the blood of the intended recipient. A composition containing one or more T cells (e.g., CAR T cells) provided herein (e.g., one or more T cells expressing (e.g., engineered to express) (a) one or more CARs having the ability to bind to a myeloid-specific polypeptide (e.g., a CD33 polypeptide) and (b) one or more iCARs having the ability to bind to a class I MHC polypeptide (e.g., an HLA-A polypeptide such as an HLA-A2 polypeptide)) can be administered using any appropriate technique and to any appropriate location. A composition including one or more T cells (e.g., CAR T cells) provided herein can be administered systemically or locally. For example, a composition provided herein can be administered systemically by intravenous administration (e.g., injection or infusion) to a mammal (e.g., a human). For example, a composition including one or more T cells (e.g., CAR T cells) provided herein can be administered locally by intratumoral administration (e.g., injection into tumors) to a tumor within a mammal (e.g., a human). In some cases, one or more T cells (e.g., CAR T cells) provided herein (e.g., one or more T cells expressing (e.g., engineered to express) (a) one or more CARs having the ability to bind to a myeloid-specific polypeptide (e.g., a CD33 polypeptide) and (b) one or more iCARs having the ability to bind to a class I MHC polypeptide (e.g., an HLA-A polypeptide such as an HLA-A2 polypeptide)) can be the sole active agent administered to a mammal Attorney Docket No.44807-0483WO1 / P18190-01 (e.g., a human) having a myeloid neoplasm (e.g., a myeloid cancer such as AML) to treat the mammal. For example, a composition including one or more T cells provided herein can include the one or more engineered T cells as the sole active agent to treat a mammal (e.g., a human) having a myeloid neoplasm. In some cases, one or more T cells (e.g., CAR T cells) provided herein (e.g., one or more T cells expressing (e.g., engineered to express) (a) one or more CARs having the ability to bind to a myeloid-specific polypeptide (e.g., a CD33 polypeptide) and (b) one or more iCARs having the ability to bind to a class I MHC polypeptide (e.g., an HLA-A polypeptide such as an HLA-A2 polypeptide)) can be administered to a mammal having a myeloid neoplasm (e.g., a myeloid cancer such as AML) as a combination therapy with one or more additional agents and / or therapies used to treat a myeloid neoplasm (e.g., a myeloid cancer such as AML). For example, an anti-cancer agent can be used to treat a myeloid neoplasm. In some cases, an anti-cancer agent can be a chemotherapeutic agent. In some cases, an anti- cancer agent can be an immunotherapeutic agent (e.g., a checkpoint inhibitor). In some cases, an anti-cancer agent can be a targeted therapy (e.g., monoclonal antibodies, bispecific antibodies, and antibody drug conjugates). Examples of anti-cancer agents include, without limitation, trametinib, dabrafenib, binimetinib, selumntinib, vemurafenib, encorafenib, cobimetinib, busulfan, cisplatin, carboplatin, paclitaxel, docetaxel, nab-paclitaxel, altretamine, capecitabine, cyclophosphamide, etoposide (vp-16), gemcitabine, ifosfamide, irinotecan (cpt-11), liposomal doxorubicin, melphalan, pemetrexed, topotecan, vinorelbine, goserelin, leuprolide, tamoxifen, letrozole, anastrozole, exemestane, bevacizumab, olaparib, rucaparib, niraparib, anthracycline, cytarabine, liposomal daunorubicin-cytarabine (CPX- 351), ivosidenib, olutasidenib, enasidenib, gilteritinib, midostaurin, azacitidine, decitabine, guadecitabine, venetoclax, fludarabine, G-CSF, idarubicin, mitoxantrone, cladribine, clofarabine, melphalan, hydroxyurea, imatinib, dasatinib, nilotinib, bosutinib, ponatinib, asciminib, interferon alfa, omacetaxine mepesuccinate, anagrelide, ruxolitinib, momelotinib, fedratinib, pacritinib, pipobroman, aspirin, epoetin alfa, lenalidomide, ipilimumab, cemiplimab, dostarlimab, nivolumab, pembrolizumab, retifanlimab, tislelizumab, toripalimab, atezolizumab, avelumab, durvalumab, gemtuzumab ozogamicin, flotetuzumab, and any combinations thereof. In cases where one or more T cells (e.g., CAR T cells) Attorney Docket No.44807-0483WO1 / P18190-01 provided herein are used with one or more additional agents treat a myeloid neoplasm, the one or more additional agents can be administered at the same time (e.g., in a single composition) or independently. In some cases, one or more T cells provided herein can be administered first, and the one or more additional agents administered second, or vice versa. Examples of therapies that can be used to treat a myeloid neoplasm (e.g., a myeloid cancer such as AML) include, without limitation, surgery, radiation therapy, carbon ion therapy, proton therapy, donor lymphocyte infusions, gene editing therapies (e.g., CRISPR, prime editing, and base editing therapies), and ultraviolet B phototherapy. In cases where one or more T cells (e.g., CAR T cells) provided herein (e.g., one or more T cells expressing (e.g., engineered to express) (a) one or more CARs having the ability to bind to a myeloid-specific polypeptide (e.g., a CD33 polypeptide) and (b) one or more iCARs having the ability to bind to a class I MHC polypeptide (e.g., an HLA-A polypeptide such as an HLA-A2 polypeptide)) are used in combination with one or more additional therapies used to treat a myeloid neoplasm, the one or more additional therapies can be performed at the same time or independently of the administration of one or more T cells provided herein. For example, the one or more T cells provided herein can be administered before, during, and / or after the one or more additional therapies are performed. In certain instances, a myeloid neoplasm (e.g., myeloid cancer such as AML) within a mammal can be monitored to evaluate the effectiveness of the treatment. Any appropriate method can be used to determine whether or not a mammal having a myeloid neoplasm is treated. For example, imaging techniques or laboratory assays can be used to assess the number of cancer cells and / or the size of a tumor present within a mammal. For example, imaging techniques or laboratory assays can be used to assess the location of cancer cells and / or a tumor present within a mammal. The invention will be further described in the following examples, which do not limit the scope of the invention described in the claims. Attorney Docket No.44807-0483WO1 / P18190-01 EXAMPLES Example 1: CAR-T Cells Having the Ability to Bind Polymorphic HLA Alleles This Example describes the design of CAR T cells of that specifically target patient myeloid and AML cells, while sparing donor-derived myeloid cells. A schematic of the designed system can be as shown in Figure 1. Screening CD33-CAR designs for optimal killing of CD33+target cells, while sparing CD33- target cells CARs were designed and cloned to contain an CD33 scFv, either a CD8α or IgG4 hinge, either a CD28 or CD8 transmembrane region, either a CD28 or 4-1BB intracellular costimulatory domain, and a CD3 zeta (ζ) intracellular signaling domain. The CD3ζ domain either contained an extra glutamine residue or did not, which was referred to as Q or no Q in construct design. The constructs were then transcribed in vitro and the RNA was transfected into primary T cells. After transfection, T cells were co-cultured with either CD33+AML cell lines or with AML cell lines where CD33 was knocked out (CD33- AML cells). The CAR containing a CD33 scFv in conjunction with a CD8α hinge, CD28 transmembrane region, CD28 intracellular co-stimulatory domain, and CD3ζ signaling domain that contained the extra glutamine was further examined. The CAR containing a CD33 scFv in conjunction with a CD8α hinge, CD28 transmembrane region, CD28 intracellular co-stimulatory domain, and CD3ζ signaling domain that contained the extra glutamine was then screened against 10 different CD33 T cell receptor (TCR) CAR designs. Included in those designs was a construct that placed the CD33 scFv, either with or without an EAAAK (SEQ ID NO:27) linker, on the constant region of the alpha chain of the T cell receptor. A split CAR design that placed the variable heavy and variable light chains on the constant regions of either the alpha or beta chain of the T cell receptor was also tested. Both orientations were tested and different lengths of EAAAK (SEQ ID NO:27) linkers were also tested. TCR CAR and various CAR designs were cloned into homology-directed repair templates and were edited into primary T cells using CRISPR knock-in. Edited T cells were co-cultured with either CD33+AML cells or CD33- AML cells. The CAR design, the TCR CAR with CD33 scFv on the constant region Attorney Docket No.44807-0483WO1 / P18190-01 of the alpha chain and no linker, and the TCR CAR containing the variable heavy chain on the constant region of the alpha chain and the variable light region on the constant region of the beta chain, all with a short EAAAK (SEQ ID NO:27) linker were further examined. Screening CD33-CAR+HLA-A2 iCAR combinations for optimal killing of CD33+ / HLA- A2- target cells while sparing CD33+ / HLA-A2+target cells CD33-CARs and TCR CARs were then cloned into homology-directed repair templates (HDRTs) containing one of three possible iCAR constructs. All constructs contained a BB7.2 scFv, which binds HLA-A2. The first iCAR option had a CD8 hinge, CD8 transmembrane region, and PD-1 intracellular signaling domain. The second option contained the same CD8 hinge and transmembrane regions, and a LIR-1 intracellular signaling domain. The third option contained a hinge, transmembrane region, and an intracellular domain derived from LIR-1. Each combination of CAR and iCAR was cloned with either the CAR first in the HDRT transcript or with the iCAR first. The HDRTs were then knocked-in to primary T cells using CRISPR. Edited T cells were co-cultured with acute myeloid leukemia cell lines that were either CD33+and HLA- A2+or CD33+and HLA-A2-. Constructs were assessed on efficacy based on specific killing of HLA-A2- cells, but not HLA-A2+cells. The top performing combinations were TCR CAR alpha no linker with the all LIR-1 iCAR and the split TCR CAR VH on α, VL on β, short EAAAK (SEQ ID NO:27) linker with the all LIR-1 iCAR. Both combinations performed better with the iCAR placed before the CAR in the HDRT. Efficacy of CD33 TCR CAR and HLA-A2 iCAR in T cells derived from multiple healthy donors CAR and iCAR combinations were edited into T cells from multiple healthy donors. Edited T cells were co-cultured with CD33+ / HLA-A2+AML cells or with CD33+ / HLA-A2- AML cells. Constructs were assessed for specificity based on ability to kill target cells that were HLA-A2- while preserving cells that are HLA-A2+. Attorney Docket No.44807-0483WO1 / P18190-01 Example 2: CAR-T Cells Having the Ability to Bind Polymorphic HLA Alleles to Treat Leukemia Patients Undergoing Bone Marrow Transplantation This Example demonstrates that CAR T cells that specifically target patient myeloid and AML cells, while sparing donor-derived myeloid cells (e.g., CAR T cells designed in Example 1) can be used to treat AML patients without causing bone marrow toxicity. For example, CD33-CAR+and HLA-A2 iCAR+T cells protected donor cells while killing recipient cells. Methods Cloning and in vitro Transcription To clone the CAR constructs for RNA transfection, DNA constructs containing desired hinge, transmembrane, co-stimulatory, and stimulatory domains were codon- optimized and synthesized by GeneArt. GeneArt Strings from GeneArt were then cloned into plasmids containing the anti-CD33 scFv and a T7 transcription start site. In vitro transcription was then performed using a T7 mScript Standard mRNA Production kit (CellScript Cat. No. C-MSC100625). Successful in vitro transcription was confirmed via observation of correctly sized RNA on Agilent Tapestation. To clone CAR and TCR CAR constructs for CRISPR knock-in, the anti-CD33 scFv was cloned into plasmids designed to be homology-directed repair templates (HDRTs) for CRISPR knock-in of TCR CARs or CARs at the T cell receptor alpha chain constant region (TRAC) locus. These plasmids contain homology arms that bind the TRAC locus, an EF-1α promoter, and an SV40 termination sequence. The constructs were designed to either attach the anti-CD33 scFv in its entirety to the alpha chain of a murine TCR alpha chain constant domain (with or without a linker) or to split the VH and VL chains of the anti-CD33 scFv between the alpha and beta constant domains of a murine TCR (with either a short or long linker). Some of the CAR constructs from RNA transfection were also cloned into HDRT plasmids. HDRT sequences were amplified via PCR using Q5 Hot Start High-Fidelity 2X Master Mix (New England BioLabs Cat. No. M0494X) and purified using AMPure beads (Beckman Coulter Cat. No. NC9959336). Size and purity of the HDRTs were verified using gel electrophoresis. TCR CAR and CAR constructs were turned into CAR and iCAR Attorney Docket No.44807-0483WO1 / P18190-01 constructs by cloning in an iCAR sequence either before or after the CAR sequence. The iCAR sequences encode an anti-HLA-A2 scFv with either a CD8-derived hinge and transmembrane domain with a PD-1 derived intracellular signaling domain or a LIR-1- derived intracellular signaling domain, or a LIR-1-derived hinge and transmembrane domain with a LIR-1-derived intracellular signaling domain. HDRTs from these CAR and iCAR plasmids were amplified via PCR using Q5 Hot Start High-Fidelity 2X Master Mix and purified using AMPure beads. Size and purity of the HDRTs were verified using gel electrophoresis. T Cell Isolation and Activation Peripheral blood mononuclear cells (PBMCs) were collected from whole blood of healthy donors using a Ficoll-Paque (Cytiva Cat. No.17-5442-02) gradient. PBMCs from seven different healthy donors, varying in HLA-A alleles, were used. Primary T cells were purified from human PBMCs using a human T cell isolation kit from StemCell Technologies (Cat. No.17951). T cells were activated using CD3 / CD28 Dynabeads (ThermoFisher Scientific Cat. No.11132D), which were removed after 48 hours. T cells were kept in RPMI- 1640 (ThermoFisher Scientific Cat. No.30-2001) with 10% fetal bovine serum (ThermoFisher Scientific Cat. No. A5669701), 1% penicillin-streptomycin (ThermoFisher Scientific Cat. No.15140-163), 100 IU / mL recombinant human IL-2 (Prometheus Therapeutics and Diagnostics), and 5 ng / mL of recombinant human IL-7 (Biolegend Cat. No. 581906). T cells were maintained at 37°C with 5% CO2and passaged every 2 or 3 days for at least 10 days before use in co-culture. Cell Lines HL-60 (ATCC Cat. No. CCL-240) cells were cultured in IMDM (ATCC Cat. No.30- 2005) with 20% fetal bovine serum (ThermoFisher Scientific Cat. No. A5669701), and 1% penicillin-streptomycin (ThermoFisher Scientific Cat. No.15140-163). THP-1 (ATCC Cat. No. TIB-202) cells were cultured in RPMI-1640 (ThermoFisher Scientific Cat. No.30-2001) with 10% fetal bovine serum, 1% penicillin-streptomycin, and 0.05mM 2-mercaptoethanol (ThermoFisher Scientific Cat. No.21985023). MOLM-14 (DSMZ ACC #777) cells were Attorney Docket No.44807-0483WO1 / P18190-01 cultured in RPMI-1640 with 10% fetal bovine serum, and 1% penicillin-streptomycin. All cells were maintained at 37°C with 5% CO2 and passaged every 3 or 4 days. Target Cell Line Generation CRISPR knock-outs of CD33 and HLA-A2 were performed using the Alt-R CRISPR- Cas9 system (IDT). The sequence for the crRNA region of the CD33 Alt-R Cas9 sgRNA is GGCCGGGTTCTAGAGTGCCA (SEQ ID NO:42). The sequence for the crRNA region of the HLA-A2 Alt-R Cas9 sgRNA is GCTGCGACGTGGGGTCGGAC (SEQ ID NO:43). The sgRNAs were resuspended at 100 µM in Nuclease-Free Duplex Buffer (IDT Cat. No.11-01- 03-01) and 100 pmol of sgRNA was complexed with 50pmol of Cas9 (IDT) and incubated for 15 min at room temperature.5e5 cells resuspended in Opti-MEM (ThermoFisher Scientific Cat. No.31985070) were added up to 20 µL in a 0.1 cm cuvette (Bio-Rad Cat. No. 165-2089). Cells were electroporated at 140V for 10ms (THP-1) or 160V for 10ms (HL-60). using the BTX ECM 2001 Electro Cell Manipulator (Harvard Apparatus). Cells were recovered in prewarmed complete growth media. Cells were then single cell plated and after 2-3 weeks were assessed for either CD33 or HLA-A2 expression using flow cytometry. The clones with the lowest expression of the target were pooled to create a polyclonal knock-out cell line. CRISPR knock-ins of HLA-A2 were performed using the Alt-R CRISPR-Cas12a (Cpf1) system (IDT). The knock-in was performed in a two-step approach. The first step used crRNAs targeted to the 5’ and 3’ UTR of the endogenous HLA-A locus to insert an HDRT containing homology arms for the 5’ and 3’ UTRs, an EF-1α promoter, and either a truncated NGFR or a puromycin resistance gene for selection of edited cells. The sequences of the crRNAs were CAGAGAAGCCAATCAGTGTCG (SEQ ID NO:44) and CAGAAACAAAGTCAGGGTTCT (SEQ ID NO:45). The HDRT inserted the promoter and selection marker in opposite orientation of the endogenous HLA-A gene. The HDRT also created two new crRNA binding sites that would be used for the second editing step. The crRNAs for the second editing step were CGTTAATCGCGTATAATACGG (SEQ ID NO:46) and CATATTGCGCGTATAGTCGCG (SEQ ID NO:47). For the second editing step, the HDRT contained homology arms against the 5’ and 3’ UTR and the complete Attorney Docket No.44807-0483WO1 / P18190-01 genomic sequence of HLA-A2. For both editing steps, 250 pmol of each crRNA was mixed with 125 pmol of Cas12a (Cpf1) (IDT) and 187.5 pmol of Cpf1 Electroporation Enhancer (IDT) to make two separate crRNA mixes that were then incubated at room temperature for 15 min. After incubation, both crRNA mixes were pooled and 1.5 µg of HDRT was added. Then, 2e6 cells resuspended in P3 buffer (Lonza Cat. No. V4XP-3024) were added and the mixture was transferred to 100 µL cuvettes. Cells were electroporated using the EN138 pulse code on a 4D-Nucleofector X Unit (Lonza Cat. No. AAF-1003X). Cells were recovered in prewarmed complete growth media. Cells were then single cell plated and after 2-3 weeks were assessed for HLA-A2 expression using flow cytometry. The clones that fully expressed HLA-A2 were pooled to create a polyclonal knock-in cell line. T Cell Electroporation For RNA transfection, primary T cells that were at least ten days post-activation were resuspended in cold Opti-MEM at a concentration of 2.5e7 cells / ml.100 µL of cells was then mixed with 0.5 µg in vitro transcribed RNA and transferred to 0.2 cm cuvettes (Bio-Rad Cat. No.1652086). The cells were electroporated using a BTX ECM 2001 Electro Cell Manipulator at 200 V for 16 ms. The cells were recovered in prewarmed media lacking IL-2 and IL-7 until use in co-culture. For CRISPR knock-in, CD3 / CD28 Dynabeads were removed from primary T cells 48 hours post-activation. Two crRNAs were used, targeting the TRAC and TRBC loci. The sequences of these crRNAs were GAGTCTCTCAGCTGGTACAC (SEQ ID NO:48) and GCCCTATCCTGGGTCCACTC (SEQ ID NO:49).250 pmol of each of these crRNAs was incubated with 125 pmol of Cas12a (Cpf1) and 187.5 pmol of Cpf1 Electroporation Enhancer to make two separate crRNA mixes and then the mixes were incubated for 15 minutes at room temperature. Following incubation, these individual RNPs were pooled and mixed with 0.5 µg of HDRT. Primary T cells were resuspended in P3 buffer and 5e6 T cells were mixed with the RNPs and HDRT. This mixture was then added to 100 µL cuvettes and electroporated using the EH115 pulse code on a Lonza 4D-Nucleofector X Unit. Cells were recovered in prewarmed media lacking cytokines and following a 1-hour incubation at 37°C with 5% CO2cells were transferred to prewarmed media containing IL-2 and IL-7. Attorney Docket No.44807-0483WO1 / P18190-01 Co-Culture For co-cultures with RNA transfected T cells, the T cells were used 5 hours post- electroporation. T cells were mixed with either HL-60 CD33+ or one of two different clones of HL-60 CD33- AML cancer cell lines at an E:T of 1:1. Cells were resuspended in 200 µL cytokine-free RPMI-1640 and added to flat-bottom 96-well plates. The co-cultures were left for between 40-56 hours at 37°C with 5% CO2. For co-cultures with CRISPR KI T cells, the T cells were used at least 10 days post- electroporation. The T cells were incubated in cytokine-free media for a day prior to co- culture. T cells were mixed with AML cancer cell lines at an E:T of 1 edited T cell (normalized based on editing rate) to 1 cancer cell. Cells were suspended in 200 µL cytokine- free RPMI-1640 and added to flat-bottom 96-well plates. The AML cancer cell lines used include HL-60 CD33+; one of two different clones of HL-60 CD33-; THP-1 CD33+, HLA- A2+; THP-1 CD33+, 95% HLA-A2-; THP-1 CD33-, HLA-A2+; THP-1 CD33+, HLA-A2-; HL-60 CD33+, HLA-A2+; MOLM-14 CD33+, HLA-A2+; and MOLM-14 CD33+, HLA- A2-. The co-cultures were left for between 40-60 hours at 37°C with 5% CO2. ELISA At the end of co-culture, 96-well plates were centrifuged at 500 xg for 5 min and the top 100 µL of media was removed. Co-culture media was diluted 10x and analyzed for presence of IFN-γ using an IFN-γ ELISA (R&D Systems Cat. No. PDIF50C). Concentrations of IFN-γ in each well are as shown. Flow Cytometry The remaining 100 µL of co-culture was analyzed for cytoxicity via flow cytometry. Cells were stained with Fixable Near-IR Live / Dead Dye (ThermoFisher Cat. No. L34975) and antibodies against CD33 (Biolegend Cat. No.366606), HLA-A2 (Biolegend Cat. No. 343306), and CD2 (Biolegend Cat. No.300230). Cells were analyzed using an Intellicyt flow cytometer (Sartorius). For CAR-only co-cultures, cancer cell line populations were gated based on absence of Fixable Near-IR Live / Dead Dye, absence of CD2, and either presence of CD33 (HL-60 CD33+) or absence (HL-60 CD33-). Counts of cancer cells gained from this gating strategy were then normalized to wells containing only cancer cells and mock Attorney Docket No.44807-0483WO1 / P18190-01 electroporated T cells or to wells containing only cancer cells and T cells with TRAC and TRBC knocked out, but no HDRT knocked in. For CAR and iCAR co-cultures, cancer cell line populations were gated based on absence of Fixable Near-IR Live / Dead Dye, absence of CD2, presence of CD33, and either presence (THP-1 CD33+, HLA-A2+; HL-60 CD33+, HLA-A2+; or MOLM-14 CD33+, HLA-A2+) or absence (THP-1 CD33+, HLA-A2-; HL-60 CD33+, HLA-A2-; or MOLM-14 CD33+, HLA-A2-) of HLA-A2. Counts of cancer cells gained from this gating strategy were then normalized to 5000 counting bead events. Statistical Analysis and Plotting Data are presented as means ± standard deviation. All analyses were performed using Prism Version 10.2.1 (GraphPad). Images were generated using BioRender. Results Screening CD33 CAR and TCR CAR Designs for Optimal Killing of CD33+ Target AML Cells, while Sparing CD33- Target Cells To have a functioning CAR and iCAR T cell system, a CAR that has both efficacy against its target and specificity for its target is required. A panel of CD33 CAR constructs varying in hinge domains, transmembrane domains, co-stimulatory domains, and presence or absence of an extra glutamine in the CD3ζ stimulatory domain was designed and cloned into plasmids containing an anti-CD33 scFv. The CARs contained either a CD8α or IgG4 hinge, either a CD28 or CD8 transmembrane region, either a CD28 or 4-1BB intracellular co- stimulatory domain, and a CD3ζ intracellular signaling domain. RNA that was in vitro transcribed from the plasmids was then transfected into T cells and T cells were co-cultured with AML cell lines. T cell constructs were assessed for efficacy and specificity based on cytotoxicity against HL-60 CD33+ cells, but not HL-60 CD33-. The most specific and effective construct was anti-CD33 scFv in conjunction with a CD8α hinge, CD28 transmembrane region, CD28 intracellular co-stimulatory domain, and CD3ζ signaling domain that contained the extra glutamine (Figure 2A). A follow-up experiment with selected CAR constructs again showed that anti-CD33 scFv in conjunction with a CD8α hinge domain, CD28 transmembrane domain, CD28 intracellular co-stimulatory domain, and Attorney Docket No.44807-0483WO1 / P18190-01 CD3ζ signaling domain that contained the extra glutamine was the most effective and specific construct because it displayed killing of HL-60 CD33+ cells, but not either clone of HL-60 CD33- cells (Figure 2B). A panel of CD33 TCR CAR constructs was also designed to find candidate constructs that were effective at killing and specific for cells expressing CD33. These candidate TCR CAR constructs used the anti-CD33 scFv with either the entire scFv attached to the constant domain of the alpha chain of the TCR or with the variable light (VL) and variable heavy (VH) chains split between the constant domains of the alpha and beta chains of the TCR. Both orientations of VH and VL, as well as different lengths of EAAAK (SEQ ID NO:27) linkers (one or three copies of EAAAK (SEQ ID NO:27)) were tested. TCR CAR constructs, as well as selected CAR constructs, were cloned into homology-directed repair templates and edited into T cells via CRISPR knock-in. T cells were co-cultured with AML cell lines and constructs were assessed for efficacy and specificity based on cytotoxicity against HL-60 CD33+ cells, but not either clone of HL-60 CD33- cells. In addition to the CD8α hinge domain, CD28 transmembrane domain, CD28 intracellular co-stimulatory domain, and CD3ζ intracellular signaling domain that contained the extra glutamine CAR, all TCR CAR constructs were found to be effective against CD33+ cells and specific for cells expressing CD33 (Figure 3). However, the TCR CAR with anti-CD33 scFv on the constant region of the alpha chain and no linker, as well as the TCR CAR containing the variable heavy chain on the constant domain of the alpha chain and the variable light chain on the constant domain of the beta chain with a short EAAAK (SEQ ID NO:27) linker were determined to be the most effective and specific TCR CAR designs (Figure 3). Screening CD33 CAR + HLA A2 iCAR Combinations for Optimal Killing of CD33+, HLA A2- Target Cells while Sparing CD33+, HLA A2+ Target Cells The top three CD33 CAR and TCR CAR candidates were then cloned into homology- directed repair templates (HDRTs) containing one of three possible iCAR constructs. All constructs contained a BB7.2 scFv, which binds HLA-A2. The first iCAR option has a CD8α hinge domain, CD8 transmembrane domain, and PD-1 intracellular signaling domain. The second option contains the same CD8 hinge and transmembrane domains, but with a LIR-1 Attorney Docket No.44807-0483WO1 / P18190-01 intracellular signaling domain. The third option contains a hinge domain, transmembrane domain, and intracellular signaling domain all derived from LIR-1. Each combination of CAR and iCAR was cloned with either the CAR sequence or the iCAR sequence positioned first in the HDRT, as shown (Figure 4A-B). CAR + iCAR constructs were edited into T cells via CRISPR knock-in and co- cultured with AML cell lines. Following co-culture, conditioned media was assessed for concentration of IFN-γ present in the media. Constructs were assessed for efficacy and specificity based on IFN-γ expression in the presence of CD33+, HLA-A2- cells, but not CD33+, HLA-A2+ cells or CD33- cells. The top performing combinations based on efficacy and specificity against cells expressing the CAR target, but not the iCAR target were the TCR CAR alpha no linker with the all LIR-1 iCAR and the split TCR CAR VH on α, VL on β, short EAAAK (SEQ ID NO:27) linker with the all LIR-1 iCAR. Both combinations performed better with the iCAR placed before the CAR in the HDRT (Figure 5). A follow-up co-culture was done on selected CAR and iCAR constructs. Constructs were edited into T cells via CRISPR knock-in and co-cultured with AML cell lines. Constructs were assessed for efficacy and specificity based on cytotoxicity against CD33+, HLA-A2- cells, but not CD33+, HLA-A2+ cells. The constructs that best killed CD33+, HLA-A2- cells, while sparing CD33+, HLA-A2+ cells were again found to be the TCR CAR alpha no linker with the all LIR-1 iCAR and the split TCR CAR VH on α, VL on β, short EAAAK (SEQ ID NO:27) linker with the all LIR-1 iCAR (Figure 7). Efficacy of CD33 TCR CAR and HLA A2 iCAR in T cells Derived from Multiple Healthy Donors The top two performing CAR and iCAR combinations were then tested using multiple primary T cell donors with varying HLA-A alleles. Primary T cells from donors were edited via CRISPR knock-in and co-cultured with AML cells. Co-cultures were assessed for efficacy and specificity via IFN-γ expression and cytotoxicity. If the TCR CARs alone are effective, then IFN-γ will be present when the T cells are cultured with both CD33+, HLA-A2+ and CD33+, HLA-A2- cells. If the TCR CAR and iCAR in combination are effective and specific, then IFN-γ will be present when the T cells are cultured with Attorney Docket No.44807-0483WO1 / P18190-01 CD33+, HLA-A2- cells, but not CD33+, HLA-A2+ cells. IFN-γ expression was as expected for TCR CARs alone and TCR CARs in combination with an iCAR for all primary T cell donors (Figures 6A-6G). If the TCR CARs alone are effective, then they would kill both CD33+, HLA-A2+ and CD33+, HLA-A2- cells. If the TCR CAR and iCAR in combination are effective and specific, then they will kill CD33+, HLA-A2- cells, but not CD33+, HLA- A2+ cells. Cytotoxicity was as expected for TCR CARs alone and TCR CARs in combination with an iCAR for all primary T cell donors (Figures 8A-8G). Efficacy of CD33 TCR CAR and HLA A2 iCAR Against Multiple AML Cell Lines The CD33 CAR and HLA-A2 iCAR combination has been shown to be effective and specific against THP-1 AML cell lines (Figures 5-8). Next, the CAR and iCAR was tested against other AML cell lines to show that the efficacy of the construct is translatable across target cell lines. A selected TCR CAR and iCAR combination, along with its corresponding TCR CAR alone, were edited into T cells and co-cultured with either HL-60 or MOLM-14 AML cells. If the TCR CAR alone is effective, then it will kill both CD33+, HLA-A2+ and CD33+, HLA-A2- HL-60 and MOLM-14 cells. If the TCR CAR and iCAR in combination are effective and specific, then it will kill CD33+, HLA-A2- HL-60 and MOLM-14 cells, but not CD33+, HLA-A2+ HL-60 and MOLM-14 cells. Cytotoxicity was as expected for the TCR CAR alone and the TCR CAR in combination with an iCAR for all AML target cell lines (Figures 9A-B). Media from the co-cultures was also assessed for IFN-γ expression. If the TCR CAR alone is effective, then IFN-γ will be present when the T cells are cultured with both CD33+, HLA-A2+ and CD33+, HLA-A2- HL-60 and MOLM-14 cells. If the TCR CAR and iCAR in combination are effective and specific, then IFN-γ will be present when the T cells are cultured with CD33+, HLA-A2- HL-60 and MOLM-14 cells, but not CD33+, HLA-A2+ HL-60 and MOLM-14 cells. IFN-γ expression was as expected for the TCR CAR alone and the TCR CAR in combination with an iCAR for all AML target cell lines (Figure 10A-10B). Example 3: CAR-T Cells Having the Ability to Bind Polymorphic HLA Alleles and Leukemia The results in this Example re-present and expand on at least some of the results provided in other Examples. Attorney Docket No.44807-0483WO1 / P18190-01 Methods Cloning To clone CAR and TCR CAR constructs for CRISPR knock-in, the anti-CD33 scFv was cloned into plasmids designed to be homology-directed repair templates (HDRTs) for CRISPR knock-in of CARs or TCR CARs at the T cell receptor alpha chain constant region (TRAC) locus. These plasmids contain homology arms that bind the TRAC locus, an EF-1α promoter, and an SV40 termination sequence. To clone CAR constructs, DNA sequences containing desired hinge, transmembrane, co-stimulatory, and intracellular signaling domains were codon-optimized and synthesized by GeneArt. GeneArt Strings were then cloned into plasmids containing the anti-CD33 scFv using NEB HiFi Assembly. To clone TCR CARs, constructs were designed to either attach the anti-CD33 scFv in its entirety to the alpha chain of a murine TCR alpha chain constant domain (with or without a linker) or to split the VH and VL chains of the anti-CD33 scFv between the alpha and beta constant domains of a murine TCR (with either a short or long linker). Cloning was done using NEB HiFi Assembly. HDRT sequences were amplified via PCR using Q5 Hot Start High-Fidelity 2X Master Mix (New England BioLabs Cat. No. M0494X) and purified using AMPure beads (Beckman Coulter Cat. No. NC9959336). Size and purity of the HDRTs was verified using gel electrophoresis. TCR CAR and CAR constructs were turned into CAR and iCAR constructs by cloning in an iCAR sequence either before or after the CAR sequence. The iCAR sequences encode an anti-HLA-A2 scFv with either a CD8-derived hinge and transmembrane domain with a PD-1 derived intracellular signaling domain or a LIR-1- derived intracellular signaling domain, or a LIR-1-derived hinge and transmembrane domain with a LIR-1-derived intracellular signaling domain. To turn the CAR and iCAR construct into a “CoSTAR” construct, MyD88 and CD40 intracellular signaling domains were cloned into the HDRT, downstream of the intracellular domain of the TCR beta chain. Cloning was done using NEB HiFi Assembly. HDRTs from these CAR and iCAR plasmids were amplified via PCR using Q5 Hot Start High-Fidelity 2X Master Mix and purified using AMPure beads. Size and purity of the HDRTs was verified using gel electrophoresis. Attorney Docket No.44807-0483WO1 / P18190-01 T Cell Isolation and Activation Peripheral blood mononuclear cells (PBMCs) were collected from whole blood of healthy donors using a Ficoll-Paque (Cytiva Cat. No.17-5442-02) gradient. PBMCs from seven different healthy donors, varying in HLA-A alleles, were used. Primary T cells were purified from human PBMCs using a human T cell isolation kit from StemCell Technologies (Cat. No.17951). T cells were activated using CD3 / CD28 Dynabeads (ThermoFisher Scientific Cat. No.11132D), which were removed after 48 hours. T cells were kept in RPMI- 1640 (ThermoFisher Scientific Cat. No.30-2001) with 10% fetal bovine serum (ThermoFisher Scientific Cat. No. A5669701), 1% penicillin-streptomycin (ThermoFisher Scientific Cat. No.15140-163), 100 IU / mL recombinant human IL-2 (Prometheus Therapeutics and Diagnostics), and 5 ng / mL of recombinant human IL-7 (Biolegend Cat. No. 581906). T cells were maintained at 37°C with 5% CO2 and passaged every 2 or 3 days for at least 10 days before use in co-culture. Cell Lines HL-60 (ATCC Cat. No. CCL-240) cells were cultured in IMDM (ATCC Cat. No.30- 2005) with 20% fetal bovine serum (ThermoFisher Scientific Cat. No. A5669701), and 1% penicillin-streptomycin (ThermoFisher Scientific Cat. No.15140-163). THP-1 (ATCC Cat. No. TIB-202) cells were cultured in RPMI-1640 (ThermoFisher Scientific Cat. No.30-2001) with 10% fetal bovine serum, 1% penicillin-streptomycin, and 0.05mM 2-mercaptoethanol (ThermoFisher Scientific Cat. No.21985023). MOLM-14 (DSMZ ACC #777) cells were cultured in RPMI-1640 with 10% fetal bovine serum and 1% penicillin-streptomycin. OCI- M1 (DSMZ ACC #529) cells were cultured in IMDM with 20% fetal bovine serum and 1% penicillin-streptomycin. All cells were maintained at 37°C with 5% CO2and passaged every 3 or 4 days. Target Cell Line Generation CRISPR knock-outs of CD33 and HLA-A2 were performed using the Alt-R CRISPR- Cas9 system (IDT). The sequence for the crRNA region of the CD33 Alt-R Cas9 sgRNA is GGCCGGGTTCTAGAGTGCCA (SEQ ID NO:42). The sequence for the crRNA region of the HLA-A2 Alt-R Cas9 sgRNA is GCTGCGACGTGGGGTCGGAC (SEQ ID NO:43). The Attorney Docket No.44807-0483WO1 / P18190-01 sgRNAs were resuspended at 100 µM in Nuclease-Free Duplex Buffer (IDT Cat. No.11-01- 03-01) and 100 pmol of sgRNA was complexed with 50pmol of Cas9 (IDT) and incubated for 15 min at room temperature.5e5 cells resuspended in Opti-MEM (ThermoFisher Scientific Cat. No.31985070) were added up to 20 µl in a 0.1 cm cuvette (Bio-Rad Cat. No. 165-2089). Cells were electroporated at 140V for 10ms (THP-1), 80V for 10ms (OCI-M1), or 160V for 10ms (HL-60). using the BTX ECM 2001 Electro Cell Manipulator (Harvard Apparatus). Cells were recovered in prewarmed complete growth media. Cells were then single cell plated and after 2-3 weeks were assessed for either CD33 or HLA-A2 expression using flow cytometry. The clones with the lowest expression of the target were pooled to create a polyclonal knock-out cell line. CRISPR knock-ins of HLA-A2 were performed using the Alt-R CRISPR-Cas12a (Cpf1) system (IDT). The knock-in was performed in a two-step approach. The first step used crRNAs targeted to the 5’ and 3’ UTR of the endogenous HLA-A locus to insert an HDRT containing homology arms for the 5’ and 3’ UTRs, an EF-1α promoter, and either a truncated NGFR or a puromycin resistance gene for selection of edited cells. The sequences of the crRNAs were CAGAGAAGCCAATCAGTGTCG (SEQ ID NO:44) and CAGAAACAAAGTCAGGGTTCT (SEQ ID NO:45). The HDRT inserted the promoter and selection marker in opposite orientation of the endogenous HLA-A gene. The HDRT also created two new crRNA binding sites that would be used for the second editing step. The crRNAs for the second editing step were CGTTAATCGCGTATAATACGG (SEQ ID NO:46) and CATATTGCGCGTATAGTCGCG (SEQ ID NO:47). For the second editing step, the HDRT contained homology arms against the 5’ and 3’ UTR and the complete genomic sequence of HLA-A2. For both editing steps, 250 pmol of each crRNA was mixed with 125 pmol of Cas12a (Cpf1) (IDT) and 187.5 pmol of Cpf1 Electroporation Enhancer (IDT) to make two separate crRNA mixes that were then incubated at room temperature for 15 min. After incubation, both crRNA mixes were pooled and 1.5 µg of HDRT was added. Then, 2e6 cells resuspended in P3 buffer (Lonza Cat. No. V4XP-3024) were added and the mixture was transferred to 100 µl cuvettes. Cells were electroporated using the EN138 pulse code on a 4D-Nucleofector X Unit (Lonza Cat. No. AAF-1003X). Cells were recovered in prewarmed complete growth media. Cells were then single cell plated and after 2-3 weeks Attorney Docket No.44807-0483WO1 / P18190-01 were assessed for HLA-A2 expression using flow cytometry. The clones that fully expressed HLA-A2 were pooled to create a polyclonal knock-in cell line. T Cell Electroporation For CRISPR knock-in, CD3 / CD28 Dynabeads were removed from primary T cells 48 hours post-activation. Two crRNAs were used, targeting the TRAC and TRBC loci. The sequences of these crRNAs were GAGTCTCTCAGCTGGTACAC (SEQ ID NO:48) and GCCCTATCCTGGGTCCACTC (SEQ ID NO:49).250 pmol of each of these crRNAs was incubated with 125 pmol of Cas12a (Cpf1) and 187.5 pmol of Cpf1 Electroporation Enhancer to make two separate crRNA mixes and then the mixes were incubated for 15 minutes at room temperature. Following incubation, these individual RNPs were pooled and mixed with 0.5 µg of HDRT. Primary T cells were resuspended in P3 buffer and 5e6 T cells were mixed with the RNPs and HDRT. This mixture was then added to 100 µl cuvettes and electroporated using the EH115 pulse code on a Lonza 4D-Nucleofector X Unit. Cells were recovered in prewarmed media lacking cytokines and following a 1-hour incubation at 37°C with 5% CO2 cells were transferred to prewarmed media containing IL-2 and IL-7. Co-Culture For co-cultures with CRISPR KI T cells, the T cells were used at least 10 days post- electroporation. The T cells were incubated in cytokine-free media for a day prior to co- culture. T cells were mixed with AML cancer cell lines at an E:T of 1 edited T cell (normalized based on editing rate) to 1 cancer cell or 1 edited T cell to 5 cancer cells. Cells were suspended in 200 µl cytokine-free RPMI-1640 and added to flat-bottom 96-well plates. The AML cancer cell lines used include HL-60 CD33+; HL-60 CD33-; THP-1 CD33+, HLA-A2+; THP-1 CD33+, HLA-A2-; THP-1 CD33-, HLA-A2+; HL-60 CD33+, HLA-A2+; MOLM-14 CD33+, HLA-A2+; MOLM-14 CD33+, HLA-A2-; MOLM-14 CD33-, HLA-A2- ; OCI-M1 CD33+, HLA-A2+; OCI-M1 CD33+, HLA-A2-; and OCI-M1 CD33-, HLA-A2+. The co-cultures were left for between 40-60 hours at 37°C with 5% CO2. Attorney Docket No.44807-0483WO1 / P18190-01 ELISA At the end of co-culture, 96-well plates were centrifuged at 500 xg for 5 min and the top 100 µl of media was removed. Co-culture media was diluted 10x and analyzed for presence of IFN-γ using an IFN-γ ELISA (R&D Systems Cat. No. PDIF50C). Concentrations of IFN-γ in each well are as shown. Flow Cytometry The remaining 100 µl of co-culture was analyzed for cytoxicity via flow cytometry. Cells were stained with Fixable Near-IR Live / Dead Dye (ThermoFisher Cat. No. L34975) and antibodies against CD33 (Biolegend Cat. No.366606), HLA-A2 (Biolegend Cat. No. 343306), and CD2 (Biolegend Cat. No.300230). Cells were analyzed using an Attune NxT flow cytometer (ThermoFisher Scientific). For CAR-only co-cultures, cancer cell line populations were gated based on absence of Fixable Near-IR Live / Dead Dye, absence of CD2, and either presence of CD33 (HL-60 CD33+) or absence (HL-60 CD33-). Counts of cancer cells gained from this gating strategy were then normalized to counting bead events and wells containing only cancer cells and T cells with TRAC and TRBC knocked out, but no HDRT knocked in. For CAR and iCAR co-cultures, cancer cell line populations were gated based on absence of Fixable Near-IR Live / Dead Dye, absence of CD2, presence of CD33, and either presence (THP-1 CD33+, HLA-A2+; HL-60 CD33+, HLA-A2+; MOLM- 14 CD33+, HLA-A2+; or OCI-M1 CD33+, HLA-A2+) or absence (THP-1 CD33+, HLA- A2-; HL-60 CD33+, HLA-A2-; MOLM-14 CD33+, HLA-A2-; or OCI-M1 CD33+, HLA- A2-) of HLA-A2. Counts of cancer cells gained from this gating strategy were then normalized to counting bead events and wells containing only cancer cells and T cells with TRAC and TRBC knocked out, but no HDRT knocked in. Mouse Xenograft Models Female NOD.Cg-PrkdcscidIl2rgtm1Wjl / SzJ (NSG) mice were acquired at age 6–8 weeks. Mice were injected through the tail vein with equal numbers of HL-60 HLA-A2+ cells and HL-60 HLA-A2-, Luciferase+ cells. After engraftment of HL-60 cells, mice were injected through the tail vein with CAR, CAR+iCAR, or CAR+CoSTAR+iCAR T cells, which were generated via CRISPR. Peripheral blood was collected from the submandibular Attorney Docket No.44807-0483WO1 / P18190-01 vein of the mice and assessed via flow cytometry for the presence of HL-60 cells and edited T cells. Blood was collected in EDTA-treated microvettes (Sarstedt Cat. No.20.1278.100) and was then treated with ACK Lysis Buffer (ThermoFisher Scientific Cat. No. A1049201). The antibodies and stains used for flow cytometry included Fixable Near-IR Live / Dead Dye (ThermoFisher Cat. No. L34975), CD33 (Biolegend Cat. No.366606), HLA-A2 (Biolegend Cat. No.343306), CD2 (Biolegend Cat. No.300210), mouse CD45 (Biolegend Cat. No. 103140), and human CD45 (Biolegend Cat. No.368522). Both HL-60 cells and human T cells were gated based on absence of Fixable Near-IR Live / Dead Dye, presence of human CD45, and absence of mouse CD45. HL-60 cells were gated on presence of CD33 and absence of CD2. T cells were gated based on presence of CD2 and absence of CD33. Bioluminescence of the HL-60 HLA-A2- cells was measured using an In Vivo Imaging System (PerkinElmer). Mice were injected with IVISbrite D-Luciferin Ultra Bioluminescent Substrate in RediJect Solution (Revvity Cat. No.770505) prior to imaging. Thirty-one days after HL-60 injection, mice were euthanized using carbon dioxide. Spleens were harvested and weighed. Spleens were then pulverized using a pestle (CellTreat Cat. No.229480) into a 40 µm cell strainer (CellTreat Cat. No.229481). Cells were then treated with ACK Lysis Buffer and analyzed using flow cytometry in the same manner as listed above. Femurs from mice were also harvested and bone marrow was collected and passed through a 40 µm cell strainer. Cells were then treated with ACK Lysis Buffer and analyzed using flow cytometry in the same manner as listed above. Statistical Analysis and Plotting Data are presented as means ± standard deviation. All analyses were performed using Prism Version 10.2.1 (GraphPad). Images were generated using BioRender. Results Efficacy of CD33 TCR CAR and HLA-A2 iCAR in T cells against multiple AML target cell lines CAR and iCAR combinations were edited into T cells. Edited T cells were co- cultured with various CD33+ / HLA-A2+and CD33+ / HLA-A2- AML cells. Constructs were Attorney Docket No.44807-0483WO1 / P18190-01 assessed for specificity based on ability to kill target cells that are HLA-A2- while preserving cells that are HLA-A2+. Enhanced killing of CD33+ target cells through addition of co-stimulatory domains to CD33 TCR CAR in combination with HLA-A2 iCAR CAR and iCAR combinations, with the addition of co-stimulatory domains, were edited into T cells. Edited T cells were co-cultured with various CD33+ / HLA-A2+and CD33+ / HLA-A2- AML cells. Constructs were assessed for specificity based on ability to kill target cells that are HLA-A2- while preserving cells that are HLA-A2+. Addition of “CoSTAR” co-stimulatory domains increased killing of CD33+ cells without sacrificing specificity against HLA-A2- cells. Screening CD33 CAR and TCR CAR Designs for Optimal Killing of CD33+ Target AML Cells, while Sparing CD33- Target Cells To have a functioning CAR and iCAR T cell system, a CAR that has both efficacy against its target and specificity for its target is required. A panel of CD33 CAR constructs varying in hinge domains, transmembrane domains, co-stimulatory domains, and presence or absence of an extra glutamine in the CD3ζ stimulatory domain was designed and cloned into homology-directed repair template (HDRT) plasmids containing an anti-CD33 scFv. The CARs contained either a CD8α or IgG4 hinge, either a CD28 or CD8 transmembrane region, either a CD28 or 4-1BB intracellular co-stimulatory domain, and a CD3ζ intracellular signaling domain. HDRTs were amplified, purified, and then knocked into T cells using CRISPR. Edited T cells were then co-cultured with AML cell lines. T cell constructs were assessed for efficacy and specificity based on cytotoxicity against HL-60 CD33+ cells, but not HL-60 CD33-. The most specific and effective construct was anti-CD33 scFv in conjunction with a CD8α hinge, CD28 transmembrane region, CD28 intracellular co- stimulatory domain, and CD3ζ signaling domain that contained the extra glutamine (Figure 11). A panel of CD33 TCR CAR constructs was also designed to find candidate constructs that were effective at killing and specific for cells expressing CD33. These candidate TCR CAR constructs used the anti-CD33 scFv with either the entire scFv attached to the constant Attorney Docket No.44807-0483WO1 / P18190-01 domain of the alpha chain of the TCR or with the variable light (VL) and variable heavy (VH) chains split between the constant domains of the alpha and beta chains of the TCR. Both orientations of VH and VL, as well as different lengths of EAAAK (SEQ ID NO:27) linkers (one or three copies of EAAAK (SEQ ID NO:27)) were tested. TCR CAR constructs were cloned into homology-directed repair templates and edited into T cells via CRISPR knock-in. T cells were co-cultured with AML cell lines and constructs were assessed for efficacy and specificity based on cytotoxicity against HL-60 CD33+ cells, but not HL-60 CD33- cells. All TCR CAR constructs were found to be cytotoxic against CD33+ cells and specific for cells expressing CD33 (Figure 12A). Conditioned media from wells with T cells expressing TCR CAR and cancer cells was also found to have IFN-γ above that of T cells with a TRAC / TRBC KO (Figure 12B). However, the TCR CAR with anti-CD33 scFv on the constant region of the alpha chain and no linker, as well as the TCR CAR containing the variable heavy chain on the constant domain of the alpha chain and the variable light chain on the constant domain of the beta chain with a short EAAAK (SEQ ID NO:27) linker were determined to be the most effective and specific TCR CAR designs. CAR + iCAR constructs were edited into T cells via CRISPR knock-in and co- cultured with AML cell lines. Following co-culture, CAR + iCAR T cell constructs were assessed for efficacy and specificity based on cytotoxicity against CD33+, HLA-A2- cells, but not CD33+, HLA-A2+ or CD33-, HLA-A2- cells via flow cytometry (Figure 13). The top performing combinations based on efficacy and specificity against cells expressing the CAR target, but not the iCAR target were the TCR CAR alpha no linker with the all LIR-1 iCAR and the split TCR CAR VH on α, VL on β, short EAAAK (SEQ ID NO:27) linker with the all LIR-1 iCAR. Both combinations performed better with the iCAR placed before the CAR in the HDRT (Figure 13). Efficacy of CD33 TCR CAR and HLA A2 iCAR Against Multiple AML Cell Lines The CD33 TCR CAR and HLA-A2 iCAR combination was then tested in a co-culture with a mixed target cell population, containing both HLA-A2+ and HLA-A2- AML cells. A selected TCR CAR and iCAR combination, along with its corresponding TCR CAR alone, were edited into T cells and co-cultured with a mixture of HL-60 CD33+, HLA-A2+ and HL- Attorney Docket No.44807-0483WO1 / P18190-01 60 CD33+, HLA-A2- AML cells. If the TCR CAR and iCAR in combination are effective and specific, then it will kill the CD33+, HLA-A2- HL-60 cells in the well, but not the CD33+, HLA-A2+ HL-60 cells. The TCR CAR alone should kill both HL-60 cell types. Cytotoxicity was as expected for the TCR CAR alone and the TCR CAR in combination with an iCAR (Figure 14). Addition of Co-Stimulatory Domains to CD33 TCR CAR Enhances Cytotoxicity without Loss of Specificity To enhance cytotoxicity of the CD33 TCR CAR construct, MyD88 and CD40 intracellular signaling domains were cloned into the HDRT plasmid using NEB HiFi Assembly. The intracellular co-stimulatory signaling domains are located downstream of the TCR beta intracellular domain. The CD33 TCR CAR including the co-stimulatory domains, along with the HLA-A2 iCAR, was edited into T cells using CRISPR. Edited T cells were co-cultured with either HL-60, OCI-M1, or MOLM-14 AML cells. If the TCR CAR with “CoSTAR” co-stimulatory domains and iCAR in combination are effective and specific, then it will kill CD33+, HLA-A2- HL-60, OCI-M1, and MOLM-14 cells, but not CD33+, HLA- A2+ or CD33- HL-60, OCI-M1 and MOLM-14 cells. Cytotoxicity was as expected for the TCR CAR with CoSTAR in combination with an iCAR for all AML target cell lines. The addition of CoSTAR increased cytotoxicity as compared to the TCR CAR and iCAR alone, without sacrificing specificity for HLA-A2- and not HLA-A2+ cells (Figures 15A-15C). Media from the co-cultures was also assessed for IFN-γ expression. If the TCR CAR with CoSTAR in combination with the iCAR is effective and specific, then IFN-γ will be present when the T cells are cultured with CD33+, HLA-A2- HL-60, OCI-M1, and MOLM-14 cells, but not CD33+, HLA-A2+ or CD33- HL-60, OCI-M1, and MOLM-14 cells. IFN-γ expression was as expected for the TCR CAR with CoSTAR in combination with an iCAR for all AML target cell lines (Figures 16A-16C). The CD33 TCR CAR and HLA-A2 iCAR combination was then tested in a co-culture with a mixed target cell population, containing both HLA-A2+ and HLA-A2- AML cells. The TCR CAR with CoSTAR and iCAR combination was edited into T cells and co-cultured with a mixture of OCI-M1 CD33+, HLA-A2+ and OCI-M1 CD33+, HLA-A2- AML cells. If Attorney Docket No.44807-0483WO1 / P18190-01 the TCR CAR with CoSTAR and iCAR is effective and specific, then it will kill the CD33+, HLA-A2- OCI-M1 cells in the well, but not the CD33+, HLA-A2+ OCI-M1 cells. If the addition of the CoSTAR domains increases cytotoxicity, then it will kill the CD33+, HLA- A2- OCI-M1 cells better than the TCR CAR and iCAR that doesn’t contain the CoSTAR domains. The TCR CAR alone should kill both OCI-M1 cell types. Cytotoxicity was increased for the TCR CAR with CoSTAR in combination with an iCAR (Figure 17). Efficacy of CD33 TCR CAR and HLA-A2 iCAR in an in vivo xenograft model The CD33 TCR CAR and HLA-A2 iCAR was then tested in an in vivo xenograft model. Female NSG mice were injected with HL-60 AML cells, half of which were HLA- A2+ and half were HLA-A2-. Mice were then injected with either TCR CAR T cells, TCR CAR+iCAR T Cells, an irrelevant CAR T cell (CD19 CAR), or no T cells (untreated). Presence of HLA-A2+ and HLA-A2- HL-60 cells in the peripheral blood was monitored. In mice that were either untreated or treated with an irrelevant CAR T cell (CD19 CAR), both HLA-A2+ and HLA-A2- HL-60 cells grew out. In mice treated with the TCR CAR alone, growth of both HL-60 cell populations was suppressed. In mice treated with the TCR CAR+iCAR, growth of the HLA-A2- HL-60 cells was suppressed, while the HLA-A2+ HL- 60 cells grew out, showing specificity of the TCR CAR in combination with the iCAR (Figure 18). HL-60 HLA-A2- cell growth was also assessed in the mice using bioluminescence imaging. Mice were injected with a luciferin substrate and imaged using an In Vivo Imaging System (IVIS). The radiance displayed indicates bioluminescent signal originating from luciferase+, HLA-A2- HL-60 cells. Signal from the mice in the untreated and irrelevant CAR (CD19 CAR) groups was high, meanwhile signal from the TCR CAR and TCR CAR+iCAR mice remained near zero for the course of the experiment (Figure 19). After mice were euthanized, spleens and bone marrow were collected from the mice and assessed for the presence of HL-60 cells and human T cells. In the spleen, large numbers of both HLA-A2+ and HLA-A2- HL-60 cells were found in the spleens of mice that were untreated or treated with CD19 CAR. Barely any of either HL-60 cell type were found in spleens of mice treated with the TCR CAR. In mice treated with the TCR CAR and iCAR, Attorney Docket No.44807-0483WO1 / P18190-01 there was a large number of HLA-A2+ HL-60 cells in the spleens, but not HLA-A2- HL-60 cells, indicating specificity of the TCR CAR in combination with the iCAR (Figure 20). A large number of T cells were also found in the spleens of mice treated with either the TCR CAR or TCR CAR and iCAR, as compared to the untreated or CD19 CAR mice, indicating that the TCR CAR and TCR CAR+iCAR T cells persisted in the tissue better than T cells expressing an irrelevant CAR (Figure 21). HL-60 cells and T cells in the bone marrow showed similar results to the spleens, indicating specificity of the TCR CAR+iCAR and persistence of the T cells in the bone marrow of the mice (Figures 22-23). Addition of Co-Stimulatory Domains to CD33 TCR CAR Enhances Cytotoxicity in an in vivo xenograft model To enhance cytotoxicity of the CD33 TCR CAR construct, MyD88 and CD40 intracellular signaling domains were added to the TCR CAR. The CD33 TCR CAR+CoSTAR in combination with the HLA-A2 iCAR was then tested in an in vivo xenograft model. Female NSG mice were injected with HL-60 AML cells, half of which were HLA-A2+ and half were HLA-A2-. Mice were then injected with either TCR CAR- CoSTAR T cells, TCR CAR+CoSTAR+iCAR T Cells, TCR CAR+iCAR T cells, or TCR KO T cells. Presence of HLA-A2+ and HLA-A2- HL-60 cells in the peripheral blood was monitored. In mice that were treated with TCR KO T cells, both HLA-A2+ and HLA-A2- HL-60 cells grew out. In mice treated with the TCR CAR+iCAR, growth of both HL-60 populations was partially suppressed. In mice treated with the TCR CAR+CoSTAR and TCR CAR+CoSTAR+iCAR, growth of both HL-60 cell populations was completely suppressed in the peripheral blood, showing increased cytotoxicity of the TCR CAR with CoSTAR in combination with the iCAR (Figure 24). Presence of human T cells in the peripheral blood was also monitored. In mice treated with TCR KO T cells and TCR CAR+iCAR T cells, there were virtually no remaining T cells on Day 18 of the experiment. In mice treated with TCR CAR+CoSTAR or TCR CAR+CoSTAR+iCAR, there was an abundance of T cells present in the peripheral blood on Day 18, showing that the addition of the CoSTAR co-stimulatory domains enhances persistence of the edited T cells in mice (Figure 25). Attorney Docket No.44807-0483WO1 / P18190-01 HL-60 HLA-A2- cell growth was also assessed in the mice using bioluminescence imaging. Mice were injected with a luciferin substrate and imaged using an In Vivo Imaging System (IVIS). The radiance displayed indicates bioluminescent signal originating from luciferase+, HLA-A2- HL-60 cells. Signal from the mice in the TCR KO group was high, meanwhile signal from the TCR CAR+CoSTAR and TCR CAR+CoSTAR+iCAR mice remained at zero for the course of the experiment. The bioluminescent signal was higher in the TCR CAR+iCAR mice, indicating that the addition of the CoSTAR co-stimulatory domains enhanced cytotoxicity towards the HLA-A2- HL-60 cells (Figure 26). Example 4: Exemplary CD33 Polypeptides This Example provides an amino acid sequence of a human CD33 polypeptide (SEQ ID NO:15). The bolded / outlined amino acid sequence of this human CD33 polypeptide depicts the extracellular domain (SEQ ID NO:1). MPLLLLLPLLWAGALAMDPNFWLQVQESVTVQEGLCVLVPCTFFHPIPYYDKNS PVHGYWFREGAIISRDSPVATNKLDQEVQEETQGRFRLLGDPSRNNCSLSIVDA RRRDNGSYFFRMERGSTKYSYKSPQLSVHVTDLTHRPKILIPGTLEPGHSKNLT CSVSWACEQGTPPIFSWLSAAPTSLGPRTTHSSVLIITPRPQDHGTNLTCQVKFA GAGVTTERTIQLNVTYVPQNPTTGIFPGDGSGKQETRAGVVHGAIGGAGVTALL ALCLCLIFFIVKTHRRKAARTAVGRNDTHPTTGSASPKHQKKSKLHGPTETSSCSGA APTVEMDEELHYASLNFHGMNPSKDTSTEYSEVRTQ (SEQ ID NO:15) Example 5: Exemplary Antigen-Binding Domains That Can Bind a CD33 Polypeptide This Example provides amino acid sequences of exemplary antigen-binding domains that can bind a human CD33 polypeptide. Attorney Docket No.44807-0483WO1 / P18190-01 VH domain with CDRs annotated: QVQLQQPGAEVVKPGASVKMSCKASGYTFTSYYIHWIKQTPGQGLEWVGVIYPGN DDISYNQKFQGKATLTADKSSTTAYMQLSSLTSEDSAVYYCAREVRLRYFDVWGQG TTVTVSS (SEQ ID NO:16) Nucleic acid sequence encoding SEQ ID NO:16: CAGGTTCAGCTGCAGCAGCCTGGCGCCGAGGTTGTGAAACCTGGCGCCTCTGTG AAGATGTCCTGCAAGGCCAGCGGCTACACCTTCACCAGCTACTACATCCACTGGA TCAAGCAGACCCCAGGCCAAGGCCTGGAATGGGTCGGAGTGATCTACCCCGGCA ACGACGACATCAGCTACAACCAGAAGTTCCAGGGCAAAGCCACACTGACCGCCG ACAAGTCTAGCACCACAGCCTACATGCAGCTGTCCAGCCTGACCAGCGAAGATAG CGCCGTGTACTACTGCGCCAGAGAAGTGCGGCTGCGGTACTTTGATGTGTGGGGC CAGGGAACCACCGTGACCGTTTCTTCT (SEQ ID NO:17) VL domain with CDRs annotated: Nucleic acid sequence encoding SEQ ID NO:18: GAGATCGTGCTGACTCAGAGCCCTGGCTCTCTGGCTGTTTCTCCTGGCGAGCGCG TGACCATGAGCTGCAAGAGTAGCCAGAGCGTGTTCTTCAGCAGCAGCCAGAAGA ACTACCTGGCCTGGTATCAGCAGATCCCCGGACAGTCTCCCCGGCTGCTGATCTAT TGGGCCAGCACAAGAGAAAGCGGCGTGCCCGATAGATTCACCGGCTCTGGAAGC GGCACCGACTTCACCCTGACAATCAGCTCTGTGCAGCCCGAGGACCTGGCCATCT ACTACTGTCACCAGTACCTGAGCAGCCGGACCTTTGGCCAGGGCACCAAGCTGG AAATCAAGAGA (SEQ ID NO:19) Attorney Docket No.44807-0483WO1 / P18190-01 scFv with a linker and CDRs annotated: EIVLTQSPGSLAVSPGERVTMSCKSSQSVFFSSSQKNYLAWYQQIPGQSPRLLIYWAS TRESGVPDRFTGSGSGTDFTLTISSVQPEDLAIYYCHQYLSSRTFGQGTKLEIKRGGG GSGGGGSSGGGSQVQLQQPGAEVVKPGASVKMSCKASGYTFTSYYIHWIKQTPGQ GLEWVGVIYPGNDDISYNQKFQGKATLTADKSSTTAYMQLSSLTSEDSAVYYCARE VRLRYFDVWGQGTTVTVSS (SEQ ID NO:20) Example 6: Exemplary HLA-A2 Polypeptides This Example provides an amino acid sequence of a human HLA-A2 polypeptide (SEQ ID NO:21). The bolded / outlined amino acid sequence of this human HLA-A2 polypeptide depicts the extracellular domain (SEQ ID NO:8). TQFVRFDSDAASQRMEPRAPWIEQEGPEYWDGETRKVKAHSQTHRVDLGTLR GYYNQSEAGSHTVQRMYGCDVGSDWRFLRGYHQYAYDGKDYIALKEDLRSW TAADMAAQTTKHKWEAAHVAEQLRAYLEGTCVEWLRRYLENGKETLQRTDA PKTHMTHHAVSDHEATLRCWALSFYPAEITLTWQRDGEDQTQDTELVETRPA GDGTFQKWAAVVVPSGQEQRYTCHVQHEGLPKPLTLRWEPSSQPTIPIVGIIAG LVLFGAVITGAVVAAVMWRRKSSDRKGGSYSQAASSDSAQGSDVSLTACKV (SEQ ID NO:21) Example 7: Exemplary Antigen-Binding Domains That Can Bind an HLA-A2 Polypeptide This Example provides amino acid sequences of exemplary antigen-binding domains that can bind a human HLA-A2 polypeptide. VH domain with CDRs annotated: QVQLQQSGPELVKPGASVKMSCKASGYTFTSYHIQWVKQRPGQGLEWIGWIYPGD GSTQYNEKFKGKTTLTADKSSSTAYMLLSSLTSEDSAIYFCAREGTYYAMDYWGQG TSVTVSS Attorney Docket No.44807-0483WO1 / P18190-01 (SEQ ID NO:22) Nucleic acid encoding SEQ ID NO:22: CAGGTCCAGCTGCAGCAGTCTGGCCCTGAACTTGTGAAACCTGGCGCCTCCGTG AAGATGAGCTGTAAAGCCAGCGGCTACACCTTCACCAGCTACCACATCCAGTGG GTCAAGCAGAGGCCTGGACAGGGACTCGAGTGGATCGGCTGGATCTATCCTGGC GACGGCAGCACCCAGTACAACGAGAAGTTCAAGGGCAAGACCACACTGACCGC CGACAAGAGCAGCAGCACAGCCTACATGCTGCTGAGCAGCCTGACCAGCGAGG ACAGCGCCATCTACTTTTGTGCCAGAGAGGGCACCTACTACGCCATGGATTATTG GGGCCAGGGCACCAGCGTGACAGTCTCTTCT (SEQ ID NO:23) VL domain with CDRs annotated: DIVMTQAPLSLPVSLGDQVSISCRSSQSIVHSNGNTYLEWYLQKPGQSPKLLIYKVSN RFSGVPDRFSGSGSGTDFTLKISRVEAEDLGVYYCFQGSHVPRTFGGGTKLELKRTG LS (SEQ ID NO:24) Nucleic acid encoding SEQ ID NO:24: GATATCGTGATGACACAGGCCCCTCTGAGCCTGCCTGTGTCTCTGGGAGATCAGG TGTCCATCAGCTGTCGGAGCAGCCAGAGCATCGTGCACAGCAACGGCAACACCT ACCTGGAATGGTATCTGCAGAAGCCCGGACAGAGCCCCAAGCTGCTGATCTACAA GGTGTCCAACCGGTTCAGCGGCGTGCCCGATAGATTTTCTGGCAGCGGCTCTGGC ACCGACTTCACCCTGAAGATCTCCAGAGTGGAAGCCGAGGACCTGGGCGTGTACT ACTGCTTCCAAGGCAGCCACGTGCCAAGAACCTTTGGCGGCGGAACAAAGCTGG AACTGAAGAGAACCGGCCTGAGC (SEQ ID NO:25) Attorney Docket No.44807-0483WO1 / P18190-01 scFv with a linker and CDRs annotated: QVQLQQSGPELVKPGASVKMSCKASGYTFTSYHIQWVKQRPGQGLEWIGWIYPGD GSTQYNEKFKGKTTLTADKSSSTAYMLLSSLTSEDSAIYFCAREGTYYAMDYWGQG TSVTVSSGGGGSGGGGSGGGGSDIVMTQAPLSLPVSLGDQVSISCRSSQSIVHSNGNT YLEWYLQKPGQSPKLLIYKVSNRFSGVPDRFSGSGSGTDFTLKISRVEAEDLGVYYC FQGSHVPRTFGGGTKLELKRTGLS (SEQ ID NO:26) Example 8: Exemplary Linkers and Hinges That Can Used to Design a CAR or an iCAR This Example provides amino acid sequences of exemplary linkers and hinges that can be used to design a CAR and / or an iCAR. linkers: EAAAK (SEQ ID NO:27) GSGGGGSSGGGS (SEQ ID NO:28) GGGGSGGGGSGGGGS (SEQ ID NO:29) hinges: CD8 hinge TTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIY (SEQ ID NO:30) IgG4 hinge ESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFN WYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSS IEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPEN NYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSL GKM (SEQ ID NO:31) Attorney Docket No.44807-0483WO1 / P18190-01 LIR-1 hinge: YGSQSSKPYLLTHPSDPLELVVSGPSGGPSSPTTGPTSTSGPEDQPLTPTGSDPQSGLG RHLG (SEQ ID NO:32) Example 9: Exemplary Transmembrane Domains That Can Used to Design a CAR or an iCAR This Example provides amino acid sequences of exemplary transmembrane domains that can be used to design a CAR and / or an iCAR. CD8 TM domain IYIWAPLAGTCGVLLLSLVIT (SEQ ID NO:33) CD28 TM domain FWVLVVVGGVLACYSLLVTVAFIIFWV (SEQ ID NO:34) LIR-1 TM domain VIGILVAVILLLLLLLLLFLI (SEQ ID NO:35) Example 10: Exemplary Stimulatory Intracellular Signaling Domains That Can Used to Design a CAR This Example provides amino acid sequences of exemplary stimulatory intracellular signaling domains that can be used to design a CAR. CD3z intracellular signaling domain (containing the extra glutamine) RVKFSRSADAPAYQQGQNQLYNELNLGRREEYDVLDKRRGRDPEMGGKPQRRKNP QEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQA LPPR (SEQ ID NO:36) Attorney Docket No.44807-0483WO1 / P18190-01 CD3z intracellular signaling domain (without the extra glutamine) RVKFSRSADAPAYQQGQNQLYNELNLGRREEYDVLDKRRGRDPEMGGKPRRKNPQ EGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQAL PPR (SEQ ID NO:37) CD28 intracellular signaling domain RSKRSRLLHSDYMNMTPRRPGPTRKHYQPYAPPRDFAAYRS (SEQ ID NO:38) 4-1BB intracellular signaling domain KRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCEL (SEQ ID NO:39) MyD88 intracellular signaling domain MAAGGPGAGSAAPVSSTSSLPLAALNMRVRRRLSLFLNVRTQVAADWTALAEEMD FEYLEIRQLETQADPTGRLLDAWQGRPGASVGRLLELLTKLGRDDVLLELGPSIEED CQKYILKQQQEEAEKPLQVAAVDSSVPRTAELAGITTLDDPLG (SEQ ID NO:50) CD40 intracellular signaling domain KKVAKKPTNKAPHPKQEPQEINFPDDLPGSNTAAPVQETLHGCQPVTQEDGKESRIS VQERQ (SEQ ID NO:51) Example 11: Exemplary Inhibitory Intracellular Signaling Domains That Can Used to Design an iCAR This Example provides amino acid sequences of exemplary inhibitory intracellular signaling domains that can be used to design an iCAR. PD-1 intracellular signaling domain CSRAARGTIGARRTGQPLKEDPSAVPVFSVDYGELDFQWREKTPEPPVPCVPEQTEY ATIVFPSGMGTSSPARRGSADGPRSAQPLRPEDGHCSWPL Attorney Docket No.44807-0483WO1 / P18190-01 (SEQ ID NO:40) LIR-1 intracellular signaling domain LRHRRQGKHWTSTQRKADFQHPAGAVGPEPTDRGLQWRSSPAADAQEENLYAAV KHTQPEDGVEMDTRSPHDEDPQAVTYAEVKHSRPRREMASPPSPLSGEFLDTKDRQ AEEDRQMDTEAAASEAPQDVTYAQLHSLTLRREATEPPPSQEGPSPAVPSIYATLAIH (SEQ ID NO:41) Example 12: Generation of CD33-CAR+and HLA-A2 iCAR+T cells T cells are obtained from a human. Nucleic acid designed to express one or more CARs having the ability to bind to a CD33 polypeptide provided herein and nucleic acid designed to express one or more iCARs having the ability to bind to a HLA-A2 polypeptide are introduced into the T cells by transduction (e.g., viral transduction using a retroviral vector such as a lentiviral vector) or transfection such that the T cells express the CAR(s) having the ability to bind to a CD33 polypeptide and express the iCAR(s) having the ability to bind to a HLA-A2 polypeptide. Example 13: Treating AML Cells (e.g., T cells) designed to express one or more CARs having the ability to bind to a CD33 polypeptide and to express one or more iCARs having the ability to bind to an HLA-A2 polypeptide are administered to a human identified as having a CD33+AML and having received a haploidentical bone marrow transplant. The cells (e.g., T cells) engineered to express one or more CARs having the ability to bind to a CD33 polypeptide and to express one or more iCARs having the ability to bind to an HLA-A2 polypeptide are administered using intravenous injection. After the administration of cells (e.g., T cells) engineered to express one or more CARs having the ability to bind to a CD33 polypeptide and to express one or more iCARs having the ability to bind to an HLA-A2 polypeptide, the number of cancer cells within the human is reduced. Attorney Docket No.44807-0483WO1 / P18190-01 Example 14: Treating AML T cells are obtained from a human identified as having a CD33+AML. Nucleic acid designed to express one or more CARs having the ability to bind to a CD33 polypeptide provided herein and nucleic acid designed to express one or more iCARs having the ability to bind to a HLA-A2 polypeptide are introduced into the T cells by transduction (e.g., viral transduction using a viral vector such as a lentiviral vector or an AAV vector) or transfection such that the T cells express the CAR(s) having the ability to bind to a CD33 polypeptide and express the iCAR(s) having the ability to bind to a HLA-A2 polypeptide. The T cells engineered to express one or more CARs having the ability to bind to a CD33 polypeptide and to express one or more iCARs having the ability to bind to an HLA-A2 polypeptide are administered back into the human using, for example, intravenous injection. After the administration of the cells (e.g., T cells) engineered to express a one or more CARs having the ability to bind to a CD33 polypeptide and to express one or more iCARs having the ability to bind to an HLA-A2 polypeptide, the number of cancer cells within the human is reduced. OTHER EMBODIMENTS It is to be understood that while the invention has been described in conjunction with the detailed description thereof, the foregoing description is intended to illustrate and not limit the scope of the invention, which is defined by the scope of the appended claims. Other aspects, advantages, and modifications are within the scope of the following claims.

Claims

Attorney Docket No.44807-0483WO1 / P18190-01 WHAT IS CLAIMED IS:

1. A T cell comprising (a) a nucleic acid encoding a chimeric antigen receptor (CAR) that binds a myeloid-specific polypeptide present on a myeloid cell, wherein said T cell expresses said CAR, and (b) a nucleic acid encoding an inhibitory chimeric antigen receptor (iCAR) that binds a class I major histocompatibility complex (MHC) polypeptide, wherein said T cell expresses said iCAR, and wherein said iCAR, when bound to said MHC polypeptide, suppresses activation of said T cell.

2. The T cell of claim 1, wherein said myeloid-specific marker is a CD33 polypeptide.

3. The T cell of claim 2, wherein said CAR comprises (i) a heavy chain variable (VH) domain comprising a VH CDR1 that comprises, consists essentially of, or consists of the amino acid sequence set forth in SEQ ID NO:2, a VH CDR2 that comprises, consists essentially of, or consists of the amino acid sequence set forth in SEQ ID NO:3, and a VH CDR3 that comprises, consists essentially of, or consists of the amino acid sequence set forth in SEQ ID NO:4 and / or (ii) a light chain variable (VL) domain comprising a VL CDR1 that comprises, consists essentially of, or consists of the amino acid sequence set forth in SEQ ID NO:5, a VL CDR2 that comprises, consists essentially of, or consists of the amino acid sequence set forth in SEQ ID NO:6, and a VL CDR3 that comprises, consists essentially of, or consists of the amino acid sequence set forth in SEQ ID NO:

7.

4. The T cell of claim 3, wherein said CAR comprises said (i) and said (ii).

5. The T cell of any one of claims 1-4, wherein said CAR comprises a CD28 stimulatory intracellular signaling domain or a CD3ζ stimulatory intracellular signaling domain.

6. The T cell of any one of claims 1-5, wherein said MHC polypeptide is a human leukocyte antigen (HLA)-A polypeptide.Attorney Docket No.44807-0483WO1 / P18190-01 7. The T cell of claim 6, wherein said HLA-A polypeptide is an HLA-A2 polypeptide.

8. The T cell of any one of claims 1-7, wherein said iCAR comprises (iii) a VH domain comprising a VH CDR1 that comprises, consists essentially of, or consists of the amino acid sequence set forth in SEQ ID NO:9, a VH CDR2 that comprises, consists essentially of, or consists of the amino acid sequence set forth in SEQ ID NO:10, and a VH CDR3 that comprises, consists essentially of, or consists of the amino acid sequence set forth in SEQ ID NO:11 and / or (iv) VL domain comprising a VL CDR1 that comprises, consists essentially of, or consists of the amino acid sequence set forth in SEQ ID NO:12, a VL CDR2 that comprises, consists essentially of, or consists of the amino acid sequence set forth in SEQ ID NO:13, and a VL CDR3 that comprises, consists essentially of, or consists of the amino acid sequence set forth in SEQ ID NO:

14.

9. The T cell of claim 8, wherein said iCAR comprises said (iii) and said (iv).

10. The T cell of any one of claims 1-9, wherein said iCAR comprises a PD-1 inhibitory intracellular signaling domain or a LIR-1 inhibitory intracellular signaling domain.

11. The T cell of any one of claims 1-10, wherein said T cell is obtained from a human.

12. The T cell of any one of claims 1-4, wherein said CAR comprises a MyD88 stimulatory intracellular signaling domain and / or a CD40 stimulatory intracellular signaling domain.

13. The T cell of any one of claims 1-12, wherein said CAR is a modified T cell receptor (a TCR CAR).

14. A method for treating a mammal having a myeloid neoplasm and having received a haploidentical bone marrow transplant, wherein said method comprises administering, to said mammal, a composition comprising the T cell of any one of claims 1-13, wherein said class IAttorney Docket No.44807-0483WO1 / P18190-01 MHC polypeptide is present on a myeloid cell produced by the transplanted bone marrow but is not present on a myeloid cell produced by the mammal’s bone marrow.

15. The method of claim 14, wherein said mammal is a human.

16. The method of any one of claims 14-15, wherein said myeloid neoplasm is selected from the group consisting of an acute myeloid leukemia (AML), a myeloid sarcoma, a chronic myelogenous leukemia (CML), a chronic myelomonocytic leukemia (CMML), an acute promyelocytic leukemia (APL), a juvenile myelomonocytic leukemia (JMML), a myelodysplastic syndrome, a polycythemia vera, an essential thrombocythemia, a primary myelofibrosis, a chronic neutrophilic leukemia, and a chronic eosinophilic leukemia.

17. The use of a composition comprising the T cell of any one of claims 1-13 to treat a mammal having myeloid neoplasm and having received a haploidentical bone marrow transplant.

18. The use of claim 17, wherein said mammal is a human.

19. The use of any one of claims 17-18, wherein said myeloid neoplasm is selected from the group consisting of an AML, a myeloid sarcoma, a CML, a CMML, an APL, a JMML, a myelodysplastic syndrome, a polycythemia vera, an essential thrombocythemia, a primary myelofibrosis, a chronic neutrophilic leukemia, and a chronic eosinophilic leukemia.

20. A composition comprising the T cell of any one of claims 1-13 for use in the preparation of a medicament to treat a mammal having myeloid neoplasm and having received a haploidentical bone marrow transplant.

21. A composition comprising the T cell of any one of claims 1-13 for use in the treatment of myeloid neoplasm in a mammal having received a haploidentical bone marrow transplant.Attorney Docket No.44807-0483WO1 / P18190-01 22. The use of any one of claims 20-21, wherein said mammal is a human.

23. The use of any one of claims 20-21, wherein said myeloid neoplasm is selected from the group consisting of an AML, a myeloid sarcoma, a CML, a CMML, an APL, a JMML, a myelodysplastic syndrome, a polycythemia vera, an essential thrombocythemia, a primary myelofibrosis, a chronic neutrophilic leukemia, and a chronic eosinophilic leukemia.

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