Logic-gated receptors and methods of making and using

Abstract

This document provides logic-gated receptors and methods for using such logic-gated receptors. For example, logic-gated receptors including (a) an antigen-triggered proteolysis receptor (ATPR) and (b) a chimeric antigen receptor (CAR) are provided. Also provided are methods and materials for making and using such logic-gated receptors. For example, methods and materials for generating cells (e.g., immune cells such as T cells) expressing a logic-gated receptor (logic-gated cells) are provided. Logic-gated cells provided herein can (1) bind a first antigen via an ATPR present in the logic-gated receptor, but are unable to bind an antigen via a CAR present in the logic-gated receptor, and (2) upon binding of the first antigen can release the ATPR such that the CAR is free to bind a second antigen, where the logic-gated cell is activated when the CAR binds the second antigen.

Description

Attorney Docket No. 44807-0518WO1 / P18835-01LOGIC-GATED RECEPTORS AND METHODS OF MAKING AND USINGCROSS-REFERENCE TO RELATED APPLICATIONSThis application claims the benefit of U. S. Patent Application Serial No. 63 / 788,447, filed on April 14, 2025. The disclosure of the prior application is considered part of, and is incorporated by reference in, the disclosure of this application.STATEMENT REGARDING FEDERAL FUNDINGThis invention was made with government support under grants CA006973 and CA153952 awarded by the National Institutes of Health. The government has certain rights in the invention.TECHNICAL FIELDThis document relates to logic-gated receptors and methods for using such logicgated receptors. For example, this document provides logic-gated receptors including (a) an antigen-triggered proteolysis receptor (ATPR) and (b) a chimeric antigen receptor (CAR). This document also provides methods and materials for making and using such logic-gated receptors. For example, this document provides methods and materials for generating cells (e.g., immune cells such as T cells) expressing a logic-gated receptor provided herein (also referred to herein as logic-gated cells). Logic-gated cells provided herein can (1) bind a first antigen via an ATPR present in the logic-gated receptor, but are unable to bind an antigen via a CAR present in the logic-gated receptor, and (2) upon binding of the first antigen can release the ATPR such that the CAR is free to bind a second antigen, where the logic-gated cell is activated when the CAR binds the second antigen.BACKGROUNDThe use of NOT-gated logic in CAR T cells has been investigated to prevent normal cell toxicity (Fedorov et al., Sci Transl Med 5:215ra172 (2013); Hwang et al., Proc Natl AcadSci USA 118:e2022410118 (2021); Hamburger et al., Mol Imm unol 128:298-310 (2020); and Richards et al., Blood Cancer Discov 2:648-665 (2021)). In this approach, simultaneous co-ligation of CAR and an inhibitory CAR (iCAR) on normal cells prevents TAttorney Docket No. 44807-0518WO1 / P18835-01cell activation. Similar in concept, other groups have proposed the development of AND-gated CAR T cells that are activated upon co-ligation of two tumor specific antigens (Salzer et al., Nat Commun 11:4166 (2020); and Tousley et al., Nature 615: 507-516 (2023)). These approaches require that two receptors co-localize to function effectively, which may require that target antigens also be co-localized at sufficient density and have similar geometry (Partin et al., Front Immunol 15:1304765 (2024)).SUMMARYThis document is based, on least in part, on logic-gated receptors (e.g., AND-gated receptors) that were designed to operate at the cell surface via the serial engagement of receptors (e.g., instead of co-engagement of receptors). The logic-gated receptors provided herein, also referred to as Multi -ATVtigen Triggered Immune. Synapse (MANTIS) CARs, rewire the spatial mechanisms of T cell activation. For example, logic-gated receptors provided herein include (a) an ATPR and (b) a CAR, where the ATPR blocks antigen binding of the CAR. When the logic-gated receptor is expressed by a T cell, the ATPR is free to bind its target antigen, but the CAR is blocked from binding its target antigen by the bulky ATPR (e.g., by the extracellular domain (ECD) of the ATPR such as a CD45 ECD). When the ATPR binds its target antigen, the ATPR undergoes a conformational change that exposes cryptic proteolysis sites within the ATPR (e.g., within the ECD of the ATPR), thus releasing the ATPR from the logic-gated receptor and generating a free CAR, where the free CAR is no longer inhibited from binding its target antigen. When the free CAR binds its target antigen, the T cell is activated, resulting in logic-gated activity.This document provides logic-gated receptors (e.g., AND-gated receptors such as MANTIS CARs) as well as methods and materials involved in making and using such logicgated receptors. For example, this document provides logic-gated receptors including (a) an ATPR and (b) a CAR. This document also provides methods and materials for using such logic-gated receptors (e.g., to treat cancer). For example, this document provides methods and materials for generating cells (e.g., immune cells such as T cells) that express one or more logic-gated receptors provided herein. As described herein, when a CAR T cell expressing a logic-gated receptor provided herein (e.g., a logic-gated receptor including (a)Attorney Docket No. 44807-0518WO1 / P18835-01an ATPR and (b) a CAR) can (1) bind a first antigen via an ATPR present in the logic-gated receptor, but are unable to bind an antigen via a CAR present in the logic-gated receptor, and (2) upon binding of the first antigen can release the ATPR such that the CAR is free to bind a second antigen, where the logic-gated cell is activated when the CAR binds the second antigen. This document also provides methods and materials for using cells (e.g., immune cells such as T cell) expressing one or more logic-gated receptors in an adoptive cell therapy (e g., a CAR T cell therapy) to treat a mammal (e.g., a human such as a human having cancer).Having the ability to precisely and flexibly control CAR T cell function using logicgated cells provided herein (e.g., cells engineered to express a logic-gated receptor including (a) an ATPR and (b) a CAR) provides a unique and unrealized opportunity to treat cancer while minimizing or even eliminating adverse impacts such as on-target / off-tumor toxicity. In addition, the logic-gated cells provided herein (e.g., cells engineered to express a logic-gated receptor including (a) an ATPR and (b) a CAR) can be designed to broaden the set of antigen combinations that can be targeted with engineered cells in cancer and other diseases. For example, differences in extracellular receptor sizes can be leveraged to control intracellular signal transduction pathways, paving new applications in synthetic biology and cell engineering.In general, one aspect of this document features logic-gated receptors (e.g., MANTIS CARs) including (e.g., from N-terminus to C-terminus): (a) an ATPR including: (a-i) a first antigen binding domain, (a-ii) a large extracellular domain, and (a-iii) a type I transmembrane domain including a juxtamembrane domain; and (b) a CAR including: (b-i) one or more signaling domains, (b-ii) a type II transmembrane domain, and (b-iii) a second antigen binding domain. The logic large extracellular domain can be derived from CD45 (PTPRC), CD43, CEACAM5, NOTCH 1, NOTCH2, NOTCH3, NOTCH4, PTPRB, PTPRD, PTPRF, PTPRG, PTPRH, PTPRJ (CD148), PTPRK, PTPRM, PTPRN, PTPRN1, PTPRO, PTPRQ, PTPRS, PTPRT, PTPRU, PTPRZ, and PTPRZ1, CD21, CD35, CD55, CD97, CD91, thrombomodulin, JAG1, JAG2, DLK1, DLL1, DLL3, or DLL4. The large extracellular domain can block binding of the second antigen binding domain to its target antigen. The large extracellular domain can include a proteolysis site. The proteolysis site can be a crypticAttorney Docket No. 44807-0518WO1 / P18835-01proteolysis site. The type I transmembrane domain including the juxtamembrane domain can be a CD45 transmembrane including a CD45 juxtamembrane domain. The first antigen binding domain and the second antigen binding domain can each independently be an antigen-binding fragment (Fab), a variable region of an antibody heavy chain, a variable region of a light chain, a single-domain antibody, a single chain variable fragment (scFv), an antibody, an antibody -based recognition scaffold, a non-antibody -based recognition scaffold, a receptor ligand, a receptor, a target of a non-antibody -based recognition scaffold, an extracellular matrix component, or an adhesion molecule. The first antigen binding domain and the second antigen binding domain can target different antigen. The first antigen binding domain and second antigen binding domain can target the same antigen. The ATPR can comprise, consist essentially of, or consist of the amino acid set forth in any one of SEQ ID NOs:4-19 or SEQ ID NOs: 136-140. The CAR also can include an accessory signaling module.In another aspect, this document features nucleic acid constructs including a nucleotide sequence that can encode a logic-gated receptor (e.g., a MANTIS CAR) including (e.g., from N-terminus to C -terminus): (a) an ATPR including: (a-i) a first antigen binding domain, (a-ii) a large extracellular domain, and (a-iii) a type I transmembrane domain including a juxtamembrane domain; and (b) a CAR including: (b-i) one or more signaling domains, (b-ii) a type II transmembrane domain, and (b-iii) a second antigen binding domain. The logic large extracellular domain can be derived from CD45 (PTPRC), CD43, CEACAM5, NOTCH1, NOTCH2, NOTCH3, NOTCH4, PTPRB, PTPRD, PTPRF, PTPRG PTPRH, PTPRJ (CD 148), PTPRK, PTPRM, PTPRN, PTPRN1, PTPRO, PTPRQ, PTPRS, PTPRT, PTPRU, PTPRZ, and PTPRZ1, CD21, CD35, CD55, CD97, CD91, thrombomodulin, JAG1, JAG2, DLK1, DLL1, DLL3, or DLL4. The large extracellular domain can block binding of the second antigen binding domain to its target antigen. The large extracellular domain can include a proteolysis site. The proteolysis site can be a cryptic proteolysis site. The type I transmembrane domain including the juxtamembrane domain can be a CD45 transmembrane including a CD45 juxtamembrane domain. The first antigen binding domain and the second antigen binding domain can each independently be an antigen-binding fragment (Fab), a variable region of an antibody heavy chain, a variableAttorney Docket No. 44807-0518WO1 / P18835-01region of a light chain, a single-domain antibody, a single chain variable fragment (scFv), an antibody, an antibody-based recognition scaffold, a non-antibody -based recognition scaffold, a receptor ligand, a receptor, a target of a non-antibody -based recognition scaffold, an extracellular matrix component, or an adhesion molecule. The first antigen binding domain and the second antigen binding domain can target different antigen. The first antigen binding domain and second antigen binding domain can target the same antigen. The ATPR can comprise, consist essentially of, or consist of the amino acid set forth in any one of SEQ ID NOs:4-19 or SEQ ID NOs:136-140. The CAR also can include an accessory signaling module. The nucleic acid construct can be an expression vector.In another aspect, this document features cells including a nucleic acid construct including a nucleic acid sequence that can encode a logic-gated receptor (e.g., a MANTIS CAR) including (e.g., from N-terminus to C-terminus): (a) an ATPR including: (a-i) a first antigen binding domain, (a-ii) a large extracellular domain, and (a-iii) a type I transmembrane domain including a juxtamembrane domain; and (b) a CAR including: (b-i) one or more signaling domains, (b-ii) a type II transmembrane domain, and (b-iii) a second antigen binding domain, where the cell expresses the logic-gated receptor. The logic large extracellular domain can be derived from CD45 (PTPRC), CD43, CEACAM5, NOTCH1, NOTCH2, NOTCH3, NOTCH4, PTPRB, PTPRD, PTPRF, PTPRG, PTPRH, PTPRJ(CD 148), PTPRK, PTPRM, PTPRN, PTPRN1, PTPRO, PTPRQ, PTPRS, PTPRT, PTPRU, PTPRZ, and PTPRZ1, CD21, CD35, CD55, CD97, CD91, thrombomodulin, JAG1, JAG2, DLK1, DLL1, DLL3, or DLL4. The large extracellular domain can block binding of the second antigen binding domain to its target antigen. The large extracellular domain can include a proteolysis site. The proteolysis site can be a cryptic proteolysis site. The type I transmembrane domain including the juxtamembrane domain can be a CD45 transmembrane including a CD45 juxtamembrane domain. The first antigen binding domain and the second antigen binding domain can each independently be an antigen-binding fragment (Fab), a variable region of an antibody heavy chain, a variable region of a light chain, a singledomain antibody, a single chain variable fragment (scFv), an antibody, an antibody -based recognition scaffold, a non-antibody -based recognition scaffold, a receptor ligand, a receptor, a target of a non-antibody-based recognition scaffold, an extracellular matrix component, orAttorney Docket No. 44807-0518WO1 / P18835-01an adhesion molecule. The first antigen binding domain and the second antigen binding domain can target different antigen. The first antigen binding domain and second antigen binding domain can target the same antigen. The ATPR can comprise, consist essentially of, or consist of the amino acid set forth in any one of SEQ ID NOs:4-19 or SEQ ID NOs: 136-140. The CAR also can include an accessory signaling module. The cell can be a T cell, a B cell, a monocyte, a dendiritic cell, a macrophage, a stem cell, or an NK cell.In another aspect, this document features cells including a logic-gated receptor (e.g., a MANTIS CAR) including (e.g., from N-terminus to C -terminus): (a) an ATPR including: (a-i) a first antigen binding domain, (a-ii) a large extracellular domain, and (a-iii) a type I transmembrane domain including a juxtamembrane domain; and (b) a CAR including: (b-i) one or more signaling domains, (b-ii) a type II transmembrane domain, and (b-iii) a second antigen binding domain. The logic large extracellular domain can be derived from CD45 (PTPRC), CD43, CEACAM5, NOTCH!, NOTCH2, NOTCH3, NOTCH4, PTPRB, PTPRD, PTPRF, PTPRG, PTPRH, PTPRJ (CD148), PTPRK, PTPRM, PTPRN, PTPRN1, PTPRO, PTPRQ, PTPRS, PTPRT, PTPRU, PTPRZ, and PTPRZ1, CD21, CD35, CD55, CD97, CD91, thrombomodulin, JAG1, JAG2, DLK1, DLL1, DLL3, or DLL4. The large extracellular domain can block binding of the second antigen binding domain to its target antigen. The large extracellular domain can include a proteolysis site. The proteolysis site can be a cryptic proteolysis site. The type I transmembrane domain including the juxtamembrane domain can be a CD45 transmembrane including a CD45 juxtamembrane domain. The first antigen binding domain and the second antigen binding domain can each independently be an antigen-binding fragment (Fab), a variable region of an antibody heavy chain, a variable region of a light chain, a single-domain antibody, a single chain variable fragment (scFv), an antibody, an antibody-based recognition scaffold, a non-antibody-based recognition scaffold, a receptor ligand, a receptor, a target of a non-antibody -based recognition scaffold, an extracellular matrix component, or an adhesion molecule. The first antigen binding domain and the second antigen binding domain can target different antigen. The first antigen binding domain and second antigen binding domain can target the same antigen. The ATPR can comprise, consist essentially of, or consist of the amino acid set forth in any one of SEQ ID NOs:4-19 or SEQ ID NOs: 136-140. The CAR also can include an accessory signalingAttorney Docket No. 44807-0518WO1 / P18835-01module. The cell can be a T cell, a B cell, a monocyte, a dendiritic cell, a macrophage, a stem cell, or an NK cell.In another aspect, this document features methods for treating a mammal having a disease, disorder, or condition that can benefit from targeted immune cell activation and is characterized by a cell-surface antigen. The methods can include, or consist essentially of, administering, to a mammal having a disease, disorder, or condition that can benefit from targeted immune cell activation and is characterized by a cell-surface antigen, a composition including a cell including a logic-gated receptor (e.g., a MANTIS CAR) including (e g., from N-terminus to C-terminus): (a) an ATPR including: (a-i) a first antigen binding domain, (a-ii) a large extracellular domain, and (a-iii) a type I transmembrane domain including a juxtamembrane domain; and (b) a CAR including: (b-i) one or more signaling domains, (b-ii) a type II transmembrane domain, and (b-iii) a second antigen binding domain, where at least one of the first antigen binding domain and the second antigen binding domain target the cell-surface antigen. The logic large extracellular domain can be derived from CD45 (PTPRC), CD43, CEACAM5, NOTCH 1, NOTCH2, NOTCH3, NOTCH4, PTPRB, PTPRD, PTPRF, PTPRG, PTPRH, PTPRJ (CD148), PTPRK, PTPRM, PTPRN, PTPRN1, PTPRO, PTPRQ, PTPRS, PTPRT, PTPRU, PTPRZ, and PTPRZ1, CD21, CD35, CD55, CD97, CD91, thrombomodulin, JAG1, JAG2, DLK1, DLL1, DLL3, or DLL4. The large extracellular domain can block binding of the second antigen binding domain to its target antigen. The large extracellular domain can include a proteolysis site. The proteolysis site can be a cryptic proteolysis site. The type I transmembrane domain including the juxtamembrane domain can be a CD45 transmembrane including a CD45 juxtamembrane domain. The first antigen binding domain and the second antigen binding domain can each independently be an antigen-binding fragment (Fab), a variable region of an antibody heavy chain, a variable region of a light chain, a single-domain antibody, a single chain variable fragment (scFv), an antibody, an antibody-based recognition scaffold, a non-antibody -based recognition scaffold, a receptor ligand, a receptor, a target of a non-antibody-based recognition scaffold, an extracellular matrix component, or an adhesion molecule. The first antigen binding domain and the second antigen binding domain can target different antigen. The first antigen binding domain and second antigen binding domain can target the same antigen. The ATPR canAttorney Docket No. 44807-0518WO1 / P18835-01comprise, consist essentially of, or consist of the amino acid set forth in any one of SEQ ID NOs:4-19 or SEQ ID NOs: 136-140. The CAR also can include an accessory signaling module. The cell can be a T cell, a B cell, a monocyte, a dendiritic cell, a macrophage, a stem cell, or an NK cell. The mammal can be a human. The large extracellular domain can inhibit binding of the second antigen binding domain to its target antigen. The inhibition can be steric inhibition. The binding of the first antigen binding domain to its target antigen can release the ATPR from the logic-gated receptor, thus leaving the CAR available to bind its target antigen. The CAR, when bound to its target antigen, can activate the cell. The disease, disorder, or condition can be cancer. The cancer can be an acute lymphoblastic leukemia (ALL), an acute myeloid leukemia (AML), a T cell leukemia, an anal cancer, an astrocytoma, a tetroid / rhabdoid tumor, a skin cancer, a biliary cancer, an osteosarcoma, a breast cancer, a central nervous system (CNS) cancer, a cervical cancer, a colorectal cancer, a T cell lymphoma, a diffuse intrinsic pontine glioma (DIPG), an endometrial cancer, an esophageal cancer, a ewing sarcoma, a retinablastoma, a gastric cancer, a head and neck cancer, a renal cancer, a liver cancer, a lung cancer, a neuroblastoma, a lung cancer, an oral cancer, an ovarian cancer, a pancreatic cancer, a rectal cancer, a small cell lung cancer (SCLC), a nonsmall cell lung cancer (NSCLC), a testicular cancer, or a thyroid cancer. The number of cancer cells within the mammal can be reduced following the administering step.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.Attorney Docket No. 44807-0518WO1 / P18835-01BRIEF DESCRIPTION OF THE DRAWINGSFigures 1 A-1F. Inhibiting CAR activity with CD45 ECD. Figure 1A) Design of CD19bbz CARs coupled to CD45 ECD in different ways along with control CAR designs. Figure IB) 100k 45ECD-CAR variants and controls were co-cultured with 20k NALM6 WT GFP-luciferase cells (5:1 E: T) for 72 hours and imaged with Incucyte live cell imaging. Normalized Growth represents total GFP integrated object intensity normalized by the integrated intensity at the 0 hr timepoint. Figure 1C) 50k 45ECD-CAR variants and controls were co-cultured with 100k NALM6 WT cells (1:2 E: T) for 24 hours and T cell activation was assessed via CD69 expression. 45ECD-CAR-2 cells were not activated. Figure ID) Design of 45ECD-CAR-3, with a truncated 45ECD containing only dl-d4. This domain size is ~15 nm and the same size as the immune synapse and should not prevent exclusion. Figure IE) Target cell growth kinetics of 45ECD-CAR-3 as observed via Incucyte live cell imaging as in Figure IB. Figure IF) CD69 activation of 45ECD-CAR-3 and controls as in Figure 1C. Data in Figures IB, 1C, IE, and IF are representative of n = 3 technical replicates.Figures 2A-2D. Design and construction of MANTIS-1. Figure 2A) Scheme for proposed MANTIS design, where a CAR is inhibited from binding by the bulky CD45 ECD at baseline. MANTIS is designed with an scFv N-terminal to the CD45 ECD domain, which upon ligand binding induces CD45 ECD proteolysis. This releases a CAR domain that can subsequently bind and activate a T cell in response to a second antigen. Figure 2B) Design of MANTIS-1, which was targeted to HLA-A2 and CD19 expressed on NALM6. MANTIS-1 was designed with a SNIPR core, consisting of a NOTCH1 TMD and NOTCH2 JMD. CAR controls, in type II transmembrane orientation are also depicted. Figure 2C) Expression of MANTIS-1 and CAR controls as identified by staining for myc and FLAG tags placed at the N- and C-terminus of all constructs after NGFR selection. Figure 2D) MANTIS- 1 and controls were co-cultured with NALM6 WT (CD19+ / A2+), A2 KO (CD19+), and CD 19 KO (A2+) cell lines for 72 hours at different E: T ratios and visualized via Incucyte live cell imaging. Normalized Growth represents total GFP integrated object intensity normalized by the integrated intensity at the 0 hr timepoint. Data in Figures 2C-2D representative of n = 2 experiments with 3 technical replicates per experiment.Attorney Docket No. 44807-0518WO1 / P18835-01Figures 3A-3H MANTIS leakiness is fixed with CD45 TMD & JMD. Figure 3A) MANTIS-12 design, which was created by replacing the SNIPR core in MANTIS- 1 with CD45 TMD and JMD as was used in 45ECD-CAR-2 & 3. Figure 3B) Expression of MANTIS-12 and controls as identified by staining for myc and FLAG tags placed at the N-and C-terminus of all constructs after NGFR selection. Figure 3C) 5-50k MANTIS-12 cells and controls were co-cultured with 10k of each NALM6 GFP-luciferase isogenic lines in individual wells. After 48 hrs, the fraction of viable cells was measured by Steady Gio luminescence assay. Figure 3D) IFNg secretion of MANTIS-12 and MANTIS-1 cells after co-culture at a 1:2 ratio with 100kNALM6 isogenic cell lines in individual wells. Figure 3E) Target cell killing by MANTIS- 12 and controls as measured by incucyte live cell imaging of a co-culture with 20kNALM6 GFP-luciferase isogenic lines at a 5:1 E: T ratio. Normalized Growth represents total GFP integrated object intensity normalized by the integrated intensity at the 0 hr timepoint. Figure 3F) CD69 expression on MANTIS cells and CAR controls when co-cultured with 100k NALM6 isogenic cell lines in a 1:2 E: T ratio for 24 hours. Figure 3G) 100k MANTIS-1 and MANTIS-12 cells were co-cultured with 100k NALM6 WT (CD19+ / A2+) cells overnight in the presence of gamma secretase inhibitors (GSi, DAPT), and ADAM protease inhibitors (ADAMi, BB94 & GI4023) individually and in combination. After 24 hours in culture, T cell activation was assessed via CD69 expression. Figure 3H) Updated mechanism of activation by MANTIS-12 based on observations that CD45 ECD can be shed as shown in g and CD45 TMD / JMD is not proteolyzed as shown in Figure 7B-7D.Figures 4A-4G. MANTIS specificity in mixed culture models. Figure 4A) 25k MANTIS and control CAR T cells were co-cultured with single target NALM6 A2 KO (CD 19+) and CD 19 KO (A2+) lines in the same well in a 1: 1: 1 ratio. Figure 4B) After 24 hours in co-culture, residual target cells were counted using flow cytometry. Figure 4C) T cell activation was assessed by CD69 flow staining. MANTIS- 12 cells were not activated, while MANTIS- 1 and CAR controls were activated and mediated bystandard killing of nontarget cells (n = 2 experiments, p values calculated with a two-way ANOVA with multiple comparison test). Figure 4D) Mixed target cells in vivo model. 100k NALM6 WT, 100k NALM6 A2 KO, and 400k CD19 KO cell lines were tail-vein injected in NSG mice 3 daysAttorney Docket No. 44807-0518WO1 / P18835-01prior to treatment with 10e6 CAR or MANTIS cells. 10 days after CAR administration, T cell engraftment was assessed via flow cytometry and 14 days after treatment the engrafted target cells were assessed via flow cytometry. Figure 4E) Representative flow plots showing target cell engraftment in the bone marrow and spleen of NSG mice after 14 days of treatment with CAR and MANTIS cells. Figures 4F and 4G) Counts of target cells isolated from bone marrow and spleens of NSG mice treated with CAR and MANTIS cells (n=5 mice per group, every data represents one animal; p values calculated by a two-way ANOVA of log-transformed values). MANTIS-12 shows the specific depletion only of double-target NALM6 WT cells in both bone marrow and spleens.Figures 5A-5D. MANTIS performance in a solid tumor cell line. Figure 5A) Design of exemplary MANTIS constructs targeted to EGFR and HER2 on A549 lung cancer cell lines. MANTIS designs were also created with increase potency. To increase potency, MANTIS was designed to heterodimerize extracellularly with an additional signaling domain by virtue of extracellular anti-parallel NZ and CZ leucine zippers. Figure 5B) Expression of EGFR and HER2 targeted MANTIS designs with and without enhanced potency as assessed via flow cytometry. Figure 5C) Target expression of EGFR and HER on wild-type A549 lung cancer cell lines and EGFR KO control. Figure 5D) 25k MANTIS13-16 constructs were co-cultured with 5k A549 WT or EGFR KO (5:1 E: T) for 180 hours and target cell growth was assessed via incucyte live cell imaging. MANTIS_16, with MyD88CD40 co-stimulation, mediated potent and specific tumor lysis of double target A549 WT. Normalized Growth represents total GFP integrated object intensity normalized by the integrated intensity at the 0 hr timepoint. Data representative of n=3 technical replicates.Figures 6A-6E. Figure 6A) CAR transgenes were knocked into the TRAC locus using CRISPR-mediated homology directed repair in primary T cells. TRBC t s also simultaneously knocked-out to ensure all cells were TCR negative. The CAR transgenes encoded a truncated NGFR (tNGFR) tag for selection of knock-in T cells via bead selection. This approach was used for all constructs employed in the study. Figure 6B) CAR and 45ECD-CAR chimeras were integrated in primary T cells, enriched with NGFR selection, and assessed for receptor expression via flow cytometry. The c-myc tag is incorporated on CD45 ECD and the FLAG tag is incorporated on the CD 19 scFv. Figure 6C) 5-50k 45ECD-Attorney Docket No. 44807-0518WO1 / P18835-01CAR chimeras and controls were incubated with 10k NALM6 GFP-luciferase cells at varying E: T ratios for 48 hours. Cell viability was measured using the Steady Gio luminescence assay (n = 3 technical replicates). Figure 6D) Flow expression 45ECD-CAR-2 and 3 constructs showing comparable expression as in Figure 6B. Figure 6E) Cytotoxicity of 45ECD-CAR-2, 45ECD-CAR-3, and CAR-2 at varying E: T ratios in the same way as in Figure 6C (n = 3 technical replicates).Figures 7A-7B. Figure 7A) Flow staining of NALM6 isogenic lines prepared via CRISPR-Cas9 mediated knock-out. NALM6 A2 KO (blue) is a polyclonal pool prepared by KO and selection of A2 negative cells by bead selection. CD 19 KO pool (grey) is a polyclonal pool prepared by mixing single cell clones. Figure 7B) 5-50k CAR controls and MANTIS cells were co-cultured with 10k NALM6 isogenic cell lines at varying E: T ratios. After 48 hours in culture, the fraction of viable cells was determined using a Steady Gio luminescence assay. Data representative of n = 2 experiments with 3 technical replicates Figures 8A-8L. Figure 8A) Design and construction of HLA-A2 targeted SNIPR transgenes which were knocked-in to the TRAC locus of primary T cells. SNIPR expression was mediated by a constitutive pGK promoter. Intracellular release of a Gal4_VP64 transcription factor mediated inducible expression of GFP. Figure 8B) Design of first batch of SNIPR receptors. SNIPR-1 is an optimized SNIPR design previously reported. SNIPR-2 is the CD45 ECD component of MANTIS- 1 with an intracellular transcription factor.MANTIS-2 is a negative control as CD45 TMD / JMD are not expected to be proteolyzed. Figures 8C and 8D) 50k SNIPR T cells were incubated with or without 50k NALM6 WT or A2 KO target cells for 48 hours. Percent of GFP+ cells and mean fluorescence intensity were measured with flow cytometry of co-cultures. CD45 ECD paired with NOTCH core leads to ligand independent GFP activity, while CD45 TMD / JMD leads to no transmembrane proteolysis. Figure 8E) Design of SNIPR-2 and SNIPR-3 mutants that are expected to reduce or increase reporter activity respectively. G318A and V319A reduce background activity of NOTCH transmembrane domains. Changing the acidic JMDof CD45 to that of NOTCH is expected to enhance proteolysis, as is the addition of an LVS gamma secretase site. Figures 8F and 8G) Same as b,c, but with the SNIPRs in Figure 8E. These results show GFP activity can be titrated based on mutations that reduce / enhance proteolysis. This suggests that CD45Attorney Docket No. 44807-0518WO1 / P18835-01ECD can be proteolyzed, but not in an antigen dependent manner. Figure 8H) Design of CD45 ECD SNIPRs with murine and human NRRs and a RAM7 sequence reported to reduce ligand independent activity. Figures 8I, 8J, and 8K) Same as in Figures 8B and 8C, but with the SNIPRs in h. Including NRRs creates ligand dependent activity of CD45 ECD SNIPRs. Figure 8L) SNIPRs were co-cultured in the presence of DAPT (gamma secretase inhibitor, GSi) or GI4023 (ADAM inhibitor, ADAMi) with A2+ NALM6 cells. After 48 hours, GFP reporter activity was assessed. Adding a NRR enables SNIPR-5 to function in a NOTCH-like manner. Constitutive activity by SNIPR-2 cannot be inhibited by these inhibitors. All data representative of n = 2 experiments with 3 technical replicates per experiment.Figures 9A-9I. Figure 9A) New MANTIS designs incorporating NRRs. Some variants included a hydrophobic RAM7 peptide. Figure 9B) Flow staining of MANTIS designs after NGFR selection. The c-myc tag is encoded on the HLA-A2 scFv, and the FLAG tag is encoded on the CD 19 scFv. All receptors expressed successfully. Figure 9Cc) 25k MANTIS cells in c were co-cultured with 25k NALM6 isogenic lines: NALM6 WT (A2+ / CD19+), NALM6 A2 KO (CD19+), and NALM6 CD 19 KO (A2+). After 72 hours, cell killing was measured via flow cytometry and normalized to counts in the TCR KO condition. NRR modifications in a did not improve specificity of MANTIS to double target cells. Figure 9D) MANTIS designs incorporating deletion of the SI domain of human NRR (MANTIS-6) and incorporating a CD45 TMD / IMD. Figure 9E) Expression of MANTIS-3, 6, 7 via flow cytometry. Figure 9F) 50k MANTIS cells were co-cultured with 50 NALM6 isogenic lines for 48 hours. Cell killing was measured by Steady Gio luminescence. These modifications also did not improve precision of MANTIS. Figure 9G) New MANTIS designs incorporating a sNRR or a human NOTCH2 NRR with CD45 TMD / JMD. (h) Expression of MANTIS designs in Figure 9G. Figure 91) 50k MANTIS cells in i were co-cultured with 50k NALM6 isogenic lines. 24 hours later, remaining target cells were assessed via flow cytometry and counts of each line were normalized to the TCR KO condition. None of these MANTIS designs improved precision either. Data in Figures 9C, 9F, and 91 are representative of n = 3 technical replicates.Figures 10A-10F. Supporting information for the in vivo experiment depicted in Fig.4D. Figure 10A) Flow characterization of the T cells that were injected in vivo. Control TAttorney Docket No. 44807-0518WO1 / P18835-01cells were used as a flow staining control only, and not injected in mice. Figure 10B) As a quality control step, T cells which were to be injected in vivo were co-cultured in a 1:1 E: T ratio with 50k NALM6 isogenic lines overnight. Cell killing was assessed via steady go luminescence. This result confirms the reactivity observed in Fig. 3 and 4. Figure 10C) Weight change of each individual mouse across the experimental timeline depicted in Fig. 4D. Grey lines depict individual mice, and black line is the average weight change across all mice. Figure 10D) On day 10, peripheral blood extracted from NSG mice were extracted and stained for NGFR to identify engrafted T cells. MANTIS and CD19 CAR controls could be identified. Figures 10F and 10G) Count of T cells identified in the bone marrow and spleens of NSG mice treated with MANTIS or CARs after 14 days. Each data point in Figures 10D, 10E, and 10F is representative of one mouse. There were n = 5 mice per group in this experiment.Figures 11A-11J. MANTIS performance in a model of HER2 on-target off-tumor toxicity. Figure 11 A) Design of MANTIS 18-19 and LINK CAR used in this study. Figure 1 IB) Expression of MANTIS-12 and controls as identified by staining for myc and FLAG tags placed at the N- and C-terminus of all constructs after NGFR selection. Figure 11C) Target cell killing by constructs in a and controls as measured by live cell imaging of a coculture with 2k SKOV3 GFP+ lines at a 5:1 E: T ratio. Normalized Growth represents total GFP integrated object intensity normalized by the integrated intensity at the 0 hr timepoint. Figure 1 ID) IFNg secretion by CAR T cells depicted in a from the co-culture depicted in c at the 72 hour timepoint. Figure 1 IE) Experimental timeline for the NSG mouse experiment to study HER2 on-target off-tumor toxicity with SKOV3 xenografts implanted in the peritoneum. Mice were treated i.p. with a high dose of Mock, HER2CAR-MC, or MANTIS-19 cells. Figure 1 IF) Anti-tumor response to CAR T cell therapy as visualized by bioluminescence imaging. Figure 11G) Quantified tumor burden in NSG mice over time. Figure 11H) Flow cytometric quantification of circulating CAR T cells in blood. Figure 1 II) Weight change and Figure 11 J) survival of NSG mice after various treatments over time. Data in c and d are representative of n = 3 technical replicates. Data in f-i representative of n = 5 mice per group. Data for MANTIS- 19 in h represent only of n = 4 mice (one mouse passed prior to first blood collection). BLI = bioluminescence imagingh Tx= treatment.Attorney Docket No. 44807-0518WO1 / P18835-01Figures 12A-12D. MANTIS-12 was expressed in Jurkat T cells and (Figure 12A) receptor expression was assessed via flow cytometry. The myc and FLAG tags are placed at the N- and C-terminus of all constructs. Figure 12B) A 1:20 volumetric dilution of Anti-c-myc beads were co-cultured with 200k Jurkat cells with or without MANTIS-12 receptor for 4 hours. Afterwards, anti-c-myc beads were isolated via magnetic separation and subsequently stained with anti-CD45 to detect proteolyzed CD45 derived from MANTIS. The stained beads were analyzed by flow cytometry. Figure 12C) Staining histograms of c-myc beads stained with anti-CD45 antibody after co-culture with Jurkat cells in A. Figure 12D) Quantified CD45+% percentages from the plots depicted in c. Data in c and D are representative of n = 2 experiments with 3 technical replicates.Figures 13A-13G. Figure 13A) Flow staining of SKOV3 isogenic lines prepared via CRISPR-Cas9 KO. Figure 13B) MANTIS- 13 and control CAR construct designs. All new designs incorporate an additional CD28 co-stimulation domain. Figure 13C) Expression of MANTIS-13 and controls as identified by staining for myc and FLAG tags placed at the N-and C-terminus of all constructs after NGFR selection. Figure 13D) Target cell killing by constructs in B and controls as measured by incucyte live cell imaging of a co-culture with 2k SKOV3 GFP+ lines at a 5:1 E: T ratio. Normalized Growth represents total GFP integrated object intensity normalized by the integrated intensity at the 0 hr timepoint. Figure 13E) Expression of EGFR and HER2 on GFP-Luciferase+ Jurkat cells engineered to artificially express these antigens. Figure 13F) 25k Jurkat target cells in E were co-cultured with 25k MANTIS-13 T cells or controls for 48 hours. The extend of target cell killing was determined by Steady Gio Luminescence assay. Fraction viable cells is luminescence relative to the Mock condition. MANTIS-13 non-specifically kills single target cells upon EGFR binding. Figure 13G) CD69 expression on MANTIS- 13 and control CAR T cells after co-culture with 25k Jurkat target cells in a 1: 1 ratio for 24 hours. Data in D, F, and G are representative of n = 3 technical replicates.Figures 14A-14H. Figure 14A) Design of HER2CAR-MC which an additional MyD88CD40-CD3z domain appended to the DARPin CAR via anti-parallel NZ and CZ leucine zippers. Figure 14B) Expression of HER2CAR and HER2CAR-MC via flow cytometry. The FLAG tag is expressed on the extracellular C-terminus of the DARPin. No c-Attorney Docket No. 44807-0518WO1 / P18835-01myc tag is present in these constructs. Addition of MC reduces the expression of CAR.Figure 14C) 5k SKOV3 WT cells were co-cultured with HER2CAR or HER2CAR-MC at varying E: T ratios. The total number of T cells in the well was kept constant via the addition of non-functional Mock T cells. Normalized Growth represents total GFP integrated object intensity normalized by the integrated intensity at the 0 hr timepoint. Figure 14D) IFNg secretion by CAR T cells from the co-culture in c at the 72-hour timepoint. The HER2C AR-MC can kill SKOV3 more potently. Figure 14E) New MANTIS constructs including the MC module. In these constructs, the 4D5 scFv was used instead of the Hl 0-2-G3 DARPin.Different anti-EGFR binders with varying affinities were also used to test the effect on MANTIS specificity. Figure 14F) Same as B but for the constructs depicted in E. Figure 14G) 25k Jurkat target cells were co-cultured with 25k MANTIS-14-17 T cells or controls for 48 hours. The extent of target cell killing was determined by Steady Gio Luminescence assay. Fraction viable cells is luminescence relative to the Mock condition. Figure 14H) CD69 expression on MANTIS-17-20 and control CAR T cells after co-culture with 25k Jurkat target cells in a 1: 1 ratio for 24 hours. MANTIS variants with a lower affinity N-terminal scFv are more specific. Data in C-D and G-H are representative of n = 3 technical replicates.Figures 15A-15C. Figure 15 A) Expression of EGFR and HER2 on Jurkat cell lines engineered to express each antigen individually or both. Figure 15B) 25k MANTIS 18-19, LINK CAR, or controls were co-cultured with 25k Jurkat cells depicted in a for 48 hours. The extent of target cell killing was determined by Steady Gio Luminescence assay. Fraction viable cells is luminescence relative to the Mock condition. Figure 15C) CD69 expression on MANTIS-16,21, LINK CAR, or control CAR T cells after co-culture with 25k Jurkat target cells in a 1: 1 ratio for 24 hours. MANTIS-21 outperforms MANTIS-16 and LINK CAR in terms of specificity. Though MANTIS-21 is less potent than MANTIS-16 and single agent CAR T cells. Data in B and C are representative of n = 3 technical replicates.Figure 16. Cell surface staining of various T cells used in the model of SKOV3 peritoneal carcinomatosis with HER2 on-target off-tumor toxicity as depicted in Fig. 11. Control T cells were not infused into NSG mice and are depicted as flow staining control.Attorney Docket No. 44807-0518WO1 / P18835-01DETAILED DESCRIPTIONThis document provides logic-gated receptors (e.g., AND-gated receptors such as MANTIS CARs) as well as methods and materials involved in making and using such logicgated receptors. For example, logic-gated receptors provided herein include (a) an ATPR and (b) a CAR, where the ATPR blocks antigen binding of the CAR. When the logic-gated receptor is expressed by a cell, the ATPR is free to bind its target antigen, but the CAR is blocked from binding its target antigen by the bulky ATPR (e.g., by the ECD of the ATPR such as a CD45 ECD). When the ATPR binds its target antigen, the ATPR undergoes a conformational change that exposes one or more cryptic proteolysis sites within the ATPR (e.g., within the ECD of the ATPR), thus releasing the ATPR from the logic-gated receptor and generating a free CAR, where the free CAR is no longer inhibited from binding its target antigen. When the free CAR binds its target antigen, the T cell is activated, resulting in logicgated activity.A logic-gated receptor provided herein (e.g., a logic-gated receptor including (a) an ATPR and (b) a CAR) can include an ATPR tethered to CAR (e.g., as a single polypeptide such as a fusion polypeptide).A logic-gated receptor provided herein (e.g., a logic-gated receptor including (a) an ATPR and (b) a CAR) can include any appropriate ATPR. An ATPR can include an antigen binding domain, an ECD, and a transmembrane domain (TMD; e.g., an anchoring TMD).In some cases, an ATPR in a logic-gated receptor provided herein (a logic-gated receptor including (a) an ATPR and (b) a CAR) can include any appropriate antigen-binding domain. Examples of antigen-binding domains include, without limitation, antigen-binding fragments (Fabs), variable regions of an antibody heavy chain (VH domains), variable regions of a light chain (VL domains), single-domain antibodies (sdAbs, also known as nanobodies), single chain variable fragments (scFvs), antibodies, antibody-based recognition scaffolds, non-antibody -based recognition scaffolds, receptor ligands, receptors, targets of a non-antibody-based recognition scaffolds, extracellular matrix components, and adhesion molecules.An antigen binding domain present in an ATPR that can be included in a logic-gated receptor provided herein (a logic-gated receptor including (a) an ATPR and (b) a CAR) canAttorney Docket No. 44807-0518WO1 / P18835-01target any appropriate antigen. In some cases, an antigen can be a cancer-specific antigen. In some cases, an antigen can be a cell surface antigen expressed by a diseased cell. Examples of antigens that can be recognized by an antigen-binding domain in ATPR in a logic-gated receptor provided herein provided herein include, without limitation, HLA-A2, CD 19, CA125, CD134, CD140 (PDGFR4), CD152, CD154, CD158, CD178, CD181 (CXCR1), CD182 (CXCR2), CD183 (CXCR3), CD19, CD2, CD20, CD21, CD210, CD22, CD23, CD246, CD25, CD252, CD253, CD261, CD262, CD27, CD273 (PD-L2), CD274 (PD-L1), CD276 (B7H3), CD279, CD28, CD295, CD33, CD339 (JAG1), CD34, CD3d, CD3e, CD4, CD40, CD45, CD48, CD5, CD52, CD59, CD66, CD7, CD70, CD71, CD72, CD73, CD79A, CD79B, CD80 (B7.1), CD86 (B7.2), CD8a, CD8b, CD94, CD95, CDla, CDlb, CDlc, CDld, CDle, CEA, EGFR, FGFR2, MUC-1, AXL, B7-H3, BCMA, BTLA, Cadherin-6, CAIX, CAIX-2, CCR4, CD1, CD123, CD133, CD137, CD147, CD20, CD22, CD30, CD33, CD38, CD3g, CD45, CD47, CD52, CD70, CD73, CD79b, CEA, Claudin-18.2, Claudin-6, CLDN18, cMET, CSF-1R, CTLA-4, DLL3, DLL4, DR5, EGFR, EpCAM, EPHA2, FAP, FGFR2b, Fibronectin EDB, TNF, Fibronectin extra-domain B, FOLR1, FRa, Fucosyl-GMl, GARP, GD2, GM3, gplOO, GPC3, GPCR5D, HER2, HER3, HGF, IFNg, IL13RA2, Integrin beta-6, L1CAM, LAG-3, MET, MSLN, MUC1, Nectin-4, NKG2A, 0X40, PD-1, PDGFRa, PD-L1, peptide-MHCs, PRAME, PSCA, PSMA, ROR1, ROR1, ROR2, SLAMF7, STEAP1, TIGIT, TIM3, Tissue factor, TROP-2, VEGF, VEGF-A, and VEGFR2.In some cases, an antigen binding domain present in an ATPR that can be included in a logic-gated receptor provided herein (e.g., a logic-gated receptor including (a) an ATPR and (b) a CAR) can be as described elsewhere (see, e.g., U. S. Patent No. 9,834,608; U. S. Patent No. 11,718,663; U. S. Patent Application Publication No. 2018 / 0265595; U. S. Patent Application Publication No. 2022 / 0267421; U. S. Patent Application Publication No.2024 / 0190981; and U. S. Patent Application Publication No. 2024 / 0052043).An ATPR in a logic-gated receptor provided herein (a logic-gated receptor including (a) an ATPR and (b) a CAR) can include any appropriate ECD. In some cases, an ECD can be a large ECD. For example, a large ECD can be a bulky (e.g., physically bulky) ECD such that it is large enough to spatially block the CAR of the logic-gated receptor from being able to bind its target antigen. For example, a large ECD can inhibit (e.g., sterically inhibit) theAttorney Docket No. 44807-0518WO1 / P18835-01CAR of the logic-gated receptor from being able to bind its target antigen. In some cases, an ECD that can be included in an ATPR of a logic-gated receptor provided herein can have an extracellular length of (e.g., when expressed in a cell, can extend from the cell surface by) 21 nm or more. For example, an ECD that can be included in an ATPR of a logic-gated receptor provided herein can have an extracellular length of from about 21 nm to about 110 nm (e.g., from about 21 nm to about 100 nm, from about 21 nm to about 80 nm, from about 21 nm to about 60 nm, from about 21 nm to about 50 nm, from about 21 nm to about 40 nm, from about 21 nm to about 30 nm, from about 25 nm to about 50 nm, from about 21 nm to about 70 nm, from about 21 nm to about 90 nm, from about 25 nm to about 100 nm, from about 50 nm to about 75 nm, from about 25 nm to about 40 nm, from about 30 nm to about 50 nm, from about 40 nm to about 70 nm, from about 50 nm to about 80 nm, or from about 70 nm to about 100 nm). An ECD that can be included in an ATPR of a logic-gated receptor provided herein can be derived from a naturally occurring polypeptide or can be a synthetic ECD. In some cases, a synthetic ECD can include one or more copies (e.g., repeats) of an ECD (e.g., an ECD derived from a naturally occurring polypeptide). Examples of ECDs that can be included in an ATPR in a logic-gated receptor provided herein provided herein include, without limitation, the ECDs from CD45 (PTPRC), CD43, CEACAM5, NOTCH1, NOTCH2, NOTCH3, NOTCH4, PTPRB, PTPRD, PTPRF, PTPRG, PTPRH, PTPRJ(CD 148), PTPRK, PTPRM, PTPRN, PTPRN1, PTPRO, PTPRQ, PTPRS, PTPRT, PTPRU, PTPRZ, and PTPRZ1, CD21, CD35, CD55, CD97, CD91, Thrombomodulin, JAG1, JAG2, DLK1, DLL1, DLL3, and DLL4. In some cases, an ECD that can be included in an ATPR in a logic-gated receptor provided herein can include one or more proteolysis sites (e.g., one or more cryptic proteolysis sites). In some cases, one or more proteolysis sites (e.g., one or more cryptic proteolysis sites) present in an ECD that can be included in an ATPR in a logic-gated receptor provided herein can be exposed upon binding of the ATPR to its target antigen (e.g., via a conformational change induced under the tension of the antigen binding). In some cases, one or more proteolysis sites (e.g., one or more cryptic proteolysis sites) can be cleaved by an enzyme (e.g., such that the ATPR is released from the logic-gated receptor). For example, when a logic-gated receptor provided herein includes an ATPR including a CD45 ECD, one or more cryptic proteolysis sites within the CD45 ECD can be exposed uponAttorney Docket No. 44807-0518WO1 / P18835-01binding of the ATPR to its target antigen such that a disintegrin and metalloproteinase (ADAM) enzyme (e.g., an endogenous ADAM enzyme) can cleave the CD45 ECD and release the ATPR from the logic-gated receptor.An ECD present in an ATPR that can be included in a logic-gated receptor provided herein (e.g., a logic-gated receptor including (a) an ATPR and (b) a CAR) can have any appropriate amino acid sequence. In some cases, an ECD present in the ATPR that can be included in a logic-gated receptor provided herein can comprise, consist essentially of, or consist of the amino acid sequence set forth in SEQ ID NO:1, shown below:QSPTPSPTGLTTAKMPSVPLSSDPLPTHTTAFSPASTFERENDFSETTTSLSPDNTSTQVSP DSLDNASAFNTTGVSSVQTPHLPTHADSQTPSAGTDTQTFSGSAANAKLNPTPGSNAISDVP GERSTASTFPTDPVSPLTTTLSLAHHSSAALPARTSNTTITANTSDAYLNASETTTLSPSGS AVISTTTIATTPSKPTCDEKYANITVDYLYNKETKLFTAKLNVNENVECGNNTCTNNEVHNL TECKNASVSISHNSCTAPDKTLILDVPPGVEKFQLHDCTQVEKADTTICLKWKNIETFTCDT QNITYRFQCGNMIFDNKEIKLENLEPEHEYKCDSEILYNNHKFTNASKIIKTDFGSPGEPQI IFCRSEAAHQGVITWNPPQRSFHNFTLCYIKETEKDCLNLDKNLIKYDLQNLKPYTKYVLSL HAYI IAKVQRNGSAAMCHFTTKSAPPSQVWNMTVSMTSDNSMHVKCRPPRDRNGPHERYHLE VEAGNTLVRNESHKNCDFRVKDLQYSTDYTFKAYFHNGDYPGEPFILHHSTSYNSKAn ECD present in an ATPR that can be included in a logic-gated receptor provided herein (e.g., a logic-gated receptor including (a) an ATPR and (b) a CAR) that consists essentially of the amino acid sequence set forth in SEQ ID NO: 1 is an ECD that has zero, one, or two amino acid substitutions within the articulated sequence of the sequence identifier (e.g., SEQ ID NO: 1), has zero, one, two, three, four, or five amino acid residues preceding the articulated sequence of the sequence identifier (e.g., SEQ ID NO:1), and / or has zero, one, two, three, four, or five amino acid residues following the articulated sequence of the sequence identifier (e.g., SEQ ID NO: 1), provided that the ECD retains the ability to block the CAR of the logic-gated receptor from being able to bind its target antigen and retains one or more cryptic proteolysis sites that can be exposed upon binding of the ATPR toAttorney Docket No. 44807-0518WO1 / P18835-01its target antigen (e.g., thus retaining the ability to be cleaved by an enzyme and release the ATPR from the logic-gated receptor).In some cases, an ECD present in an ATPR that can be included in a logic-gated receptor provided herein (e.g., a logic-gated receptor including (a) an ATPR and (b) a CAR) can be as described elsewhere (see, e.g., U. S. Patent No. 9,834,608; Xiao et al., Set. Immunol.7, eabl3995 (2022); Zhu et al., Cell 185:1431-1443 el416 (2022); and Sloas et al., Nat Biotechnol 16;41(9): 1287-1295 (2023)).An ATPR in a logic-gated receptor provided herein (e.g., a logic-gated receptor including (a) an ATPR and (b) a CAR) can include any appropriate TMD. In some cases, a TMD of an ATPR can be a type I TMD (e.g., a TMD that includes a juxtamembrane domain (JMD) immediately adjacent to the TMD on the intracellular side of the cell membrane). Examples of TMDs that can be included in an ATPR in a logic-gated receptor provided herein include, without limitation, TMDs from CD45, NOTCH, CD8 (e.g., CD8a), CD28, 0X40, TCR-alpha, and TCR-beta. In some cases, a TMD that can be included in an ATPR in a logic-gated receptor provided herein can include a CD45 TMD and a CD45 JMD.A TMD present in an ATPR that can be included in a logic-gated receptor provided herein (e.g., a logic-gated receptor including (a) an ATPR and (b) a CAR) can have any appropriate amino acid sequence. In some cases, a TMD present in an ATPR that can be included in a logic-gated receptor provided herein can comprise, consist essentially of, or consist of the amino acid sequence set forth in SEQ ID NO:2:AL I FLAFL 11 VT S IALLWL.In cases where a TMD present in an ATPR that can be included in a logic-gated receptor provided herein (e.g., a logic-gated receptor including (a) an ATPR and (b) a CAR) includes a JMD, the JMD can have any appropriate amino acid sequence. In some cases, a JMD present in an ATPR that can be included in a logic-gated receptor provided herein can comprise, consist essentially of, or consist of the amino acid sequence set forth in SEQ ID NO:3: YKIYDLHKKR.In some cases, a TMD present in an ATPR that can be included in a logic-gated receptor provided herein (e.g., a logic-gated receptor including (a) an ATPR and (b) a CAR)Attorney Docket No. 44807-0518WO1 / P18835-01can be as described elsewhere (see, e.g., U. S. Patent No. 9,834,608; Zhu et al., Cell 185:1431-1443 el416 (2022); Yang etal. Communications Biology 3: 116 (2020)).In some cases, an ATPR (or any component of an ATPR) that can be included in a logic-gated receptor provided herein (e.g., a logic-gated receptor including (a) an ATPR and (b) a CAR) can be as described in Example 5. For example, an ATPR (or any component of an ATPR) that can be included in a logic-gated receptor provided herein can comprise, consist essentially of, or consist of the amino acid set forth in any one of SEQ ID NOs:4-19 or SEQ ID NOs: 136-140.In some cases, an ATPR (or any component of an ATPR) that can be included in a logic-gated receptor provided herein (e.g., a logic-gated receptor including (a) an ATPR and (b) a CAR) can be as described elsewhere (see, e.g., Morsut et al., Cell. 11; 164(4):780-791 (2016); Zhu et al., Cell 185:1431-1443 el416 (2022); and Yang et al., Communications Biology 3:116 (2020)).A logic-gated receptor provided herein (e.g., a logic-gated receptor including (a) an ATPR and (b) a CAR) can include any appropriate CAR. In some cases, a CAR can include an antigen-binding domain, an optional hinge, a TMD, and one or more signaling domains, and an optional accessory signaling module.A CAR that can be included in a logic-gated receptor provided herein (e.g., a logicgated receptor including (a) an ATPR and (b) a CAR) can include any appropriate antigenbinding domain. Examples of antigen-binding domains include, without limitation, Fabs, VH domains, VL domain, sdAbs, scFvs, antibodies, antibody-based recognition scaffolds, non-antibody-based recognition scaffolds, receptor ligands, receptors, targets of a non-antibody-based recognition scaffolds, extracellular matrix components, and adhesion molecules.An antigen binding domain present in a CAR that can be included in a logic-gated receptor provided herein (e.g., a logic-gated receptor including (a) an ATPR and (b) a CAR) can include can target any appropriate antigen. In some cases, an antigen can be a cancerspecific antigen. In some cases, an antigen can be a cell surface antigen expressed by a diseased cell. Examples of antigens that can be recognized by an antigen-binding domain in CAR that can be included in a logic-gated receptor provided herein include, without limitation, HLA-A2, CD19, CA125, CD134, CD140 (PDGFR4), CD152, CD154, CD158,Attorney Docket No. 44807-0518WO1 / P18835-01CD178, CD181 (CXCR1), CD182 (CXCR2), CD183 (CXCR3), CD19, CD2, CD20, CD21, CD210, CD22, CD23, CD246, CD25, CD252, CD253, CD261, CD262, CD27, CD273 (PD-L2), CD274 (PD-L1), CD276 (B7H3), CD279, CD28, CD295, CD33, CD339 (JAG1), CD34, CD3d, CD3e, CD4, CD40, CD45, CD48, CD5, CD52, CD59, CD66, CD7, CD70, CD71, CD72, CD73, CD79A, CD79B, CD80 (B7.1), CD86 (B7.2), CD8a, CD8b, CD94, CD95, CDla, CDlb, CDlc, CDld, CDle, CEA, EGFR, FGFR2, MUC-1, AXL, B7-H3, BCMA, BTLA, Cadherin-6, CAIX, CAIX-2, CCR4, CD1, CD123, CD133, CD137, CD147, CD20, CD22, CD30, CD33, CD38, CD3g, CD45, CD47, CD52, CD70, CD73, CD79b, CEA, Claudin-18.2, Claudin-6, CLDN18, cMET, CSF-1R, CTLA-4, DLL3, DLL4, DR5, EGFR, EpCAM, EPHA2, FAP, FGFR2b, Fibronectin EDB, TNF, Fibronectin extra-domain B, FOLR1, FRa, Fucosyl-GMl, GARP, GD2, GM3, gplOO, GPC3, GPCR5D, HER2, HER3, HGF, IFNg, IL13RA2, Integrin beta-6, LI CAM, LAG-3, MET, MSLN, MUC1, Nectin-4, NKG2A, 0X40, PD-1, PDGFRa, PD-L1, peptide-MHCs, PRAME, PSCA, PSMA, ROR1, ROR1, ROR2, SLAMF7, STEAP1, TIGIT, TIM3, Tissue factor, TROP-2, VEGF, VEGF-A, and VEGFR2.In some cases, an antigen binding domain present in CAR that can be included in a logic-gated receptor provided herein (e.g., a logic-gated receptor including (a) an ATPR and (b) a CAR) can be as described elsewhere (see, e.g., U. S. Patent No. 11,718,663; U. S. Patent Application Publication No. 2018 / 0265595; U. S. Patent Application Publication No.2022 / 0267421; U. S. Patent Application Publication No. 2024 / 0190981; and U. S. Patent Application Publication No. 2024 / 0052043).A CAR that can be included in a logic-gated receptor provided herein (e.g., a logicgated receptor including (a) an ATPR and (b) a CAR) can include any appropriate TMD. In some cases, a TMD of a CAR can be a type II TMD. Examples of TMDs that can be included in a CAR include, without limitation, TMDs from CD8 (e.g., CD8a), TM11D, CD28, 0X40, TCR-alpha, TCR-beta, 4F2, A3KLL5, A6NGH2, A8K6Q8, ABHD2, AGRIN, AMPE, AMPN, AOC2, AOC3, ASAH2, AT1B1, AT1B2, AT1B3, ATP1B1, ATP4B, B2R8Z5, B4DIB1, B4DKB2, B4DV63, B4E028, B4GT1, B5BUQ6, B7Z2I6, B7Z9S8, B8ZZM6, BST2, C1K3N5, C9J3Y0, C9J6Q8, C9JG41, CANT1, CD209, CD40L, CD69, CD70, CEIP2, CKAP4, CL12A, CL12B, CLC2A, CLC2B, CLC2D, CLC4A, CLC4C, CLC4D,Attorney Docket No. 44807-0518WO1 / P18835-01CLC4E, CLC4G, CLC4M, CLC5A, CLC6A, CLC7A, CLCL1, CODAI, COMT, CONA1, CORIN, DPP 10, DPP4, DPP6, DYSF, E7EUS6, ECE1, EDA, ENPP1, ENPP3, ENTP6, EXTL3, F5H2B7, F5H4I5, F6WZH4, FCER2, FKRP, FOLH1, G3VOE5, GGT1, GLDN, HEPS, HG2A, IFM2, IFM3, IOD3, ITM2B, ITM2C, J3QLG7, J3QS57, J9JIC8, KELL, KKLC1, KLRD1, KLRF2, KLRG1, LCAP, MARCO, MFRP, MGA, MYOF, NALD2, NALDL, NCEH1, NEP, NKG2A, NKG2C, NKG2D, OLR1, OTOF, PCAT1, PCAT2, PHEX, PLS1, PLS4, PLVAP, PRRT1, Q1HEA1, Q53FG2, Q53ZY6, Q58I20, Q59E93, Q59FZ9, Q5STB3, Q5YLG5, Q6LEU2, Q7Z528, Q8N353, Q8WZ67, Q9NX12, SCAR5, SEPR, SGCB, SGCD, SGCG, SGCZ, SIA8B, SIM23, SLC31, SMIM1, SUIS, SYNG1, T106B, TFR1, TFR2, TFRC, TM11B, TM11E, TMEM106B, TMEM98, TMM98, TMPS2, TMPS4, TMPS5, TMPS6, TMPS7, TMPS9, TMPSD, TN13B, TNF, TNF10, TNF11, TNF12, TNF14, TNF18, TNFA, TNFL6, and TRDN.In some cases, a TMD that can be present in a CAR that can be included in a logicgated receptor provided herein (e.g., a logic-gated receptor including (a) an ATPR and (b) a CAR) can be as described elsewhere (see, e.g., Wang et al., PLOS ONE, 9(5):e96790 (2014); Brown et al., PLOS ONE 8(9)::e73225 (2013); Guo et al., Molecular Immunology 114:108-113 (2019); U. S. Patent Application Publication No. 2024 / 0076372; and International Patent Application Publication No. WO 2022 / 192691).A CAR that can be included in a logic-gated receptor provided herein (e.g., a logicgated receptor including (a) an ATPR and (b) a CAR) can include one or more of any appropriate stimulatory intracellular signaling domains. For example, CAR that can be included in a logic-gated receptor provided herein can be designed to include one, two, three, four, or five stimulatory intracellular signaling domains. When a CAR that can be included in a logic-gated receptor provided herein 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, intracellular signaling domains from CD3(^, CD28, 4- IBB, CD2,Attorney Docket No. 44807-0518WO1 / P18835-01CD4, 0X40, ICOS, BTLA, CD27, CD30, GITR, HVEM, CD8, activating, BAFFR, BLAME, BTLA, CD 100, CD 103, CD 160, CD 18, CD 19, CD 19a, CD247, CD27, CD276, CD28, CD29, CD3, CD3delta, CD3epsilon, CD3gamma, and, CD30, CD4, CD40, CD49, CD49a, CD49D, CD49f, CD69, CD7, CD84, CD8, CD8alpha, CD8beta, CD96, CD11, CD 11 a, CD 11b, CD 11c, CD lid, CDS, CEACAM1, CTLA-4, CRTAM, cytokine, DAP- 10, DNAM1, GADS, IA4, ICAM-1, CD79a, IL-2Rbeta, IL-2R, IL 7R, integrin, ITGA4, ITGA6, ITGAD, ITGAE, ITGAL, ITGAM, ITGAX, ITGB2, ITGB7, ITGB1, KIRDS2, LAT, LIGHT, LTBR, Ly9, Lyl08, LFA-1, MHC, NKG2C, NKG2D, NKp30, NKp44, NKp46, NKp80, PAG / Cbp, programmed, PSGL1, SELPLG, SLAM, SLAMF1, SLAMF4, SLAMF6, and, SLP-76, TNF, TNFR2, TNFSF14, TRANCE / RANKL, VLA1, VLA-6, MyD88, 2B4, CD22, CD79a, CD79b, CRACC, CRTAM, DAP 12, DR3, FCER1G, FCGR1A, FCGR2A, FCGR2B, FCGR3A, FCRL1, FCRL2, FCRL3, FCRL4, FCRL5, FCRL6, ITAM, KIR2DL1, KIR2DL2, KIR2DL3, KIR2DL4, KIR2DL5A, KIR2DL5B, KIR3DL1, KIR3DL2, KIR3DL3, LAG3, LILRB1, LILRB2, NKG2A, PILRB, SIRPa, TIGIT, TIM1, TIM3, TNFL6, TLR1, TLR10, TLR2, TLR3, TLR4, TLR5, TLR6, TLR7, TLR8, and TLR9. In some cases, a CAR can be designed to be a first-generation CAR having a CD3 signaling domain. In some cases, a CAR can be designed to be a second-generation CAR having two stimulatory domains (e.g. a 4- IBB signaling domain followed by a CD3(^ signaling domain). In some cases, a CAR can be designed to be a third-generation CAR having three or more stimulatory domains (e g. a 4-1BB signaling domain, a CD28 signaling domain, a MyD88CD40 domain, and a CD3(^ signaling domain).In some cases, a stimulatory intracellular signaling domain of a CAR that can be included in a logic-gated receptor provided herein (e.g., a logic-gated receptor including (a) an ATPR and (b) a CAR) can be as described elsewhere (see, e.g., International Patent Application Publication No. WO 2022 / 192691; Honikel et al., Biomolecules 12(9): 1303 (2022); and Zhao et al. Biochemical Pharmacology. 227:116439 (2024)).In some cases, a CAR that can be included in a logic-gated receptor provided herein (e.g., a logic-gated receptor including (a) an ATPR and (b) a CAR) can include an optional hinge region. In some cases, a hinge region can be located between an antigen-binding domain and a TMD of a CAR. In some cases, a hinge region can provide a CAR withAttorney Docket No. 44807-0518WO1 / P18835-01increased flexibility for the antigen-binding domain. For example, a hinge region can reduce spatial limitations of an antigen-binding domain of a CAR and its target antigen (e.g., to increase binding between an antigen-binding domain of a CAR and its target antigen).Examples of hinge regions that can be used as described herein include, without limitation, a membrane-proximal region from an IgG, a glycine-serine repeat, a membrane-proximal region from CD8, a leucine zipper domain, and a membrane-proximal region from CD28. In some cases, a hinge region of a CAR can be as described elsewhere (see, e.g., Cho et al., Cell 173(6): 1426-1438 (2018); U. S. Patent Application Publication No. 2018 / 0000914 such as U. S. Patent Application Publication No. 2018 / 0000914 at paragraph

[0168] , and Table 1; U. S. Patent Application Publication No. 2017 / 0183418 such as U. S. Patent Application Publication No. 2017 / 0183418 at paragraphs

[0034] ,

[0037] ,

[0040] , and Table 2; U. S. Patent Application Publication No. 2017 / 0183413 such as U. S. Patent Application Publication No.2017 / 0183413 at paragraph

[0116] ; and U. S. Patent Application Publication No.2017 / 0145094 such as U. S. Patent Application Publication No. 2017 / 0145094 at paragraph

[0104] ).In some cases, a CAR that can be included in a logic-gated receptor provided herein (e.g., a logic-gated receptor including (a) an ATPR and (b) a CAR) can include an optional accessory signaling module. For example, a CAR that can be included in a logic-gated receptor provided herein can include an accessory signaling module as a separate type I orientation polypeptide. An accessory signaling module can be coupled to a CAR in a logicgated receptor provided herein directly or indirectly. In some cases, an accessory signaling module can be coupled to a CAR in a logic-gated receptor provided herein via an extracellular heterodimerizing domain. Examples of extracellular heterodimerizing domains include, without limitation, leucine zippers, Fab chains, a De novo design protein, and FKBP domains. In some cases, a CAR in a logic-gated receptor provided herein can be coupled to an accessory signaling module by anti-parallel NZ and CZ leucine zippers. In some cases, an extracellular heterodimerizing domain of an accessory signaling module that can be present in a CAR that can be included in a logic-gated receptor provided herein can be as described elsewhere (see, e.g., Ghosh et al. J. Am. Chem. Soc. 122,23:5658-5659 (2000); Cho et al. Cell 173:6 1426-1438. ell (2020); Lajoie et al. Science 369(6511): 1637-1643 (2020).Attorney Docket No. 44807-0518WO1 / P18835-01An accessory signaling module that can be included in a CAR that can be included in a logic-gated receptor provided herein (e.g., a logic-gated receptor including (a) an ATPR and (b) a CAR) can include any appropriate TMD. Examples of the TMDs that can be included in an accessory signaling module included in a CAR that can be included in a logicgated receptor provided herein include, without limitation, TMDs from 4-1BB, BAFFR, BLAME, BTLA, CD100, CD103, CD11, CDlla, CDllb, CDllc, CD134, CD137, CD154, CD 16, CD 160, CD 18, CD 19, CD 19a, CD2, CD22, CD247, CD27, CD276, CD28, CD29, CD3, CD30, CD33, CD37, CD3delta, CD4, CD40, CD45, CD49, CD49a, CD49D, CD5, CD64, CD7, CD8, CD80, CD84, CD86, CD8alpha, CD8beta, CD9, CD96, CDS, CEACAM1, CRTAM, CTLA-4, cytokine, DAP-10, DNAM1, Fc, GADS, GITR, HVEM, IA4, ICAM-1, Ig, IL-2R, IL-7R, integrin, ITGA1, ITGA4, ITGA6, ITGAD, ITGAE, ITGAL, ITGAM, ITGAX, ITGB1, ITGB2, ITGB7, KIRDS2, LAT, LTBR, Ly9, MHC, NKp30, NKp44, NKp46, NKp80, OX-40, PAG / Cbp, PSGL1, SELPLG, SLAM, SLAMF1, SLAMF4, SLAMF6, SLP-76, TNFR2, TNFSF14, TRANCE / RANKL, VLA1, and VLA-6. In some cases, accessory signaling module that can be included in a CAR that can be included in a logic-gated receptor provided herein can be a CD8alpha transmembrane. In some cases, a TMD of an accessory signaling module that can be included in a CAR that can be included in a logic-gated receptor provided herein 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 accessory signaling module that can be included in a CAR that can be included in a logic-gated receptor provided herein (e.g., a logic-gated receptor including (a) an ATPR and (b) a CAR) can include any appropriate one or more signaling domains. In some cases, a signaling domain that can be included in accessory signaling module that can be included in a CAR that can be included in a logic-gated receptor provided herein can be designed to include one, two, three, four, or five stimulatory intracellular signaling domains. When a signaling domain that can be included in accessory signaling module that can be included in a CAR that can be included in a logic-gated receptor provided herein includes more than one (e.g., two, three, four, or five) stimulatory intracellular signaling domains, the signaling domain can include any appropriate combination of stimulatory intracellular signalingAttorney Docket No. 44807-0518WO1 / P18835-01domains. In some cases, an accessory signaling module 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 an accessory signaling module that can be included in a CAR that can be included in a logic-gated receptor provided herein include, without limitation, intracellular signaling domains from CD3(^, CD28, 4-1BB, CD2, CD4, 0X40, ICOS, BTLA, CD27, CD30, GITR, HVEM, CD8, activating, BAFFR, BLAME, BTLA, CD 100, CD 103, CD 160, CD 18, CD 19, CD 19a, CD247, CD27, CD276, CD28, CD29, CD3, CD3delta, CD3epsilon, CD3gamma, CD30, CD4, CD40, CD49, CD49a, CD49D, CD49f, CD69, CD7, CD84, CD8, CD8alpha, CD8beta, CD96, CD11, CDlla, CDllb, CDllc, CDlld, CDS, CEACAM1, CTLA-4, CRTAM, cytokine, DAP-10, DNAM1, GADS, IA4, ICAM-1, CD79a, IL-2Rbeta, IL-2R, IL 7R, integrin, ITGA4, ITGA6, ITGAD, ITGAE, ITGAL, ITGAM, ITGAX, ITGB2, ITGB, ITGB1, KIRDS2, LAT, LIGHT, LTBR, Ly9, Lyl08, LFA-1, MHC, NKG2C, NKG2D, NKp30, NKp44, NKp46, NKp80, PAG / Cbp, programmed, PSGL1, SELPLG, SLAM, SLAMF1, SLAMF4, SLAMF6, SLP-76, TNF, TNFR2, TNFSF14, TRANCE / RANKL, VLA1, VLA-6, MyD88, 2B4, CD22, CD79a, CD79b, CRACC, CRTAM, DAP12, DR3, FCER1G, FCGR1A, FCGR2A, FCGR2B, FCGR3A, FCRL1, FCRL2, FCRL3, FCRL4, FCRL5, FCRL6, ITAM, KIR2DL1, KIR2DL2, KIR2DL3, KIR2DL4, KIR2DL5A, KIR2DL5B, KIR3DL1, KIR3DL2, KIR3DL3, LAG3, LILRB1, LILRB2, NKG2A, PILRB, SIRPa, TIGIT, TIM1, TIM3, TNFL6, TLR1, TLR10, TLR2, TLR3, TLR4, TLR5, TLR6, TLR7, TLR8, and TLR9. In some cases, an accessory signaling module can be designed to be a first-generation accessory signaling module having a CD3y signaling domain. In some cases, an accessory signaling module can be designed to be a second-generation accessory signaling module having two stimulatory domains (e.g. a 4-1BB signaling domain followed by a CD3(^ signaling domain). In some cases, an accessory signaling module can be designed to be a third-generation accessory signaling module having three or more stimulatory domains (e.g. a 4-1BB signaling domain, a CD28 signaling domain, a MyD88CD40 domain, and a CD3(^ signaling domain). In some cases, an accessory signaling module that can be included in a CAR that can be included in a logic-gated receptor provided herein can be as described elsewhere (see, e.g., International Patent ApplicationAttorney Docket No. 44807-0518WO1 / P18835-01Publication No. WO 2022 / 192691; Honikel, M. M et al. Biomolecules 12(9): 1303 (2022); Zhao, W. et al. Biochemical Pharmacology. 227: 116439 (2024).In some cases, a CAR (or any component of a CAR) that can be included in a logicgated receptor provided herein (e.g., a logic-gated receptor including (a) an ATPR and (b) a CAR) can be as described in Example 4. For example, a CAR (or any component of a CAR) that can be included in a logic-gated receptor provided herein can comprise, consist essentially of, or consist of the amino acid set forth in any one of SEQ ID NOs:20-26.In some cases, a CAR (or any component of a CAR) that can be included in a logicgated receptor provided herein (e.g., a logic-gated receptor including (a) an ATPR and (b) a CAR) can be as described elsewhere (see, e.g., Sadelain et al., Nature 545: 423-431 (2017); June et al., NEJM 379:64-73 (2018); Labanieh et al., Nature 614:635-648 (2023); Abken, Hum Gene Ther. 32(19-20):1011-1028 (2021); Mitra et al., Front. Immunol. 14: 1188049 (2023); Honikel et al., Biomolecules 12(9): 1303 (2022); and Zhao et al., Biochemical Pharmacology. 227:116439 (2024)).This document also provides nucleic acid constructs having a nucleic acid sequence encoding a logic-gated receptor provided herein (e.g., a logic-gated receptor including (a) an ATPR and (b) a CAR). A nucleic acid construct can be a vector (e.g., a viral vector or a plasmid vector such as an expression vector). An example of a plasmid vector that can be designed to include a nucleic acid sequence encoding a logic-gated receptor provided herein includes, without limitation, expression vectors. Examples of viral vectors that can be designed to include a nucleic acid sequence encoding a logic-gated receptor provided herein include, without limitation, retroviral vectors, adenoviral-based vectors, adeno-associated virus (AAV)-based vectors, lentiviral vectors, and hybrid or chimeric viral vectors.A nucleic acid construct provided herein (e.g., a viral vector or plasmid vector such as an expression vector) can include any appropriate promoter and / or other regulatory sequences (e.g., transcription and translation initiation and termination codons) operably linked the nucleic acid sequence encoding a logic-gated receptor provided herein. A promoter used to drive expression can be a naturally occurring promotor (e.g., an endogenous) or a synthetic promotor. A promoter used to drive expression can be a constitutive promotor or a regulatable promotor. Examples of promoters that can be used toAttorney Docket No. 44807-0518WO1 / P18835-01drive expression of a logic-gated receptor provided herein as described herein include, without limitation, adenoviral promotors, EFla promoters, PGK promoters, CMV promoters, RPBSA promoters, UBC promoters, CAG promoters, ACTB promoters, and SV40 promoters.This document also provides host cells expressing (e.g., designed to express) one or more logic-gated receptors (e.g., AND-gated receptors such as MANTIS CARs) provided herein (e.g., a CAR T cell engineered to express a logic-gated receptor including (a) an ATPR and (b) a CAR). A host cell can be any type of cell. In some cases, a host cell can be an immune cell. Examples of immune cells that can be used to express one or more logicgated receptors provided herein include, without limitation, T cells, B cells, monocytes, dendiritic cells, macrophages, stem cells, and NK cells. When a T cell is designed to express one or more logic-gated receptors provided herein, the T cell can be any appropriate T cell. A T cell can be a naive T cell. Examples of T cells that can be used to generate logic-gated receptor T cells as described herein include, without limitation, cytotoxic T cells (e.g., CD4+CTLs and / or CD8+CTLs). In some cases, logic-gated receptor T cells can be generated from T cells that were obtained from a mammal (e.g., a mammal having cancer) that is to be treated with the logic-gated receptor T cells. For example, T cells can be obtained from a mammal to be treated with the materials and method described herein.Any appropriate method can be used to generate a cell expressing one or more logicgated receptors (e.g., AND-gated receptors such as MANTIS CARs) provided herein (e g., a CAR T cell engineered to express a logic-gated receptor including (a) an ATPR and (b) a CAR). For example, a nucleic acid construct provided herein (e.g., a nucleic acid construct having a nucleic acid sequence encoding a logic-gated receptor provided herein (e g., a logicgated receptor including (a) an ATPR and (b) a CAR)) can be introduced into a cell (e.g., an immune cell such as a T cell). In some cases, a nucleic acid construct provided herein can be introduced into a cell using one or more genetic editing techniques (e.g., CRISPR mediated homology directed repair). In some cases, a nucleic acid construct provided herein can be introduced into a cell by transduction (e.g., viral transduction using a viral vector) or transfection. In some cases, a nucleic acid construct provided herein can be introduced ex vivo into one or more cells. For example, ex vivo engineering of immune cells (e.g., T cells)Attorney Docket No. 44807-0518WO1 / P18835-01can include introducing a nucleic acid construct provided herein to isolated immune cells (e.g., isolated T cells) such as immune cells obtained from a mammal (e.g., from a mammal to be treated or a donor mammal. For example, ex vivo engineering of immune cells (e.g., T cells) can include introducing a nucleic acid construct provided herein to a cell line.This document also provides methods for using one or more logic-gated receptors (e.g., AND-gated receptors such as MANTIS CARs) provided herein (e.g., a CAR T cell engineered to express a logic-gated receptor including (a) an ATPR and (b) a CAR). For example, provided herein are methods for using cells (e.g., immune cells such as T cells) expressing (e.g., designed to express) one or more logic-gated receptors provided herein. In some cases, cells expressing one or more logic-gated receptors provided herein can be used to treat a mammal having any disease, disorder, and / or condition that can benefit from targeted immune cell activation. In some cases, the methods and materials provided herein can be used as an anti-senolytic. Examples of diseases, disorders, and conditions that can be treated using cells expressing one or more logic-gated receptors provided herein as described herein include, without limitation, cancers, auto-immune diseases, fibrosis, infectious diseases, and aging.Any appropriate mammal (e.g., a human) can be treated as described herein (e.g., by administering cells (e.g., immune cells such as T cells) expressing (e.g., designed to express) one or more logic-gated receptors provided herein (e.g., one or more logic-gated receptors including (a) an ATPR and (b) a CAR). Examples of mammals that can be treated as described herein include, without limitation, humans, non-human primates (e.g., monkeys), dogs, cats, horses, cows, pigs, sheep, mice, and rats. In some cases, a human can be treated by administering cells expressing one or more logic-gated receptor T provided herein to the human.In some cases, cells (e.g., immune cells such as T cells) expressing (e.g., designed to express) one or more logic-gated receptors (e.g., AND-gated receptors such as MANTIS CARs) provided herein (e.g., a CAR T cell engineered to express a logic-gated receptor including (a) an ATPR and (b) a CAR) can be used for treating mammals (e.g., humans) having cancer. For example, cells expressing one or more logic-gated receptors providedAttorney Docket No. 44807-0518WO1 / P18835-01herein 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 cancer to treat the mammal.When treating a mammal (e.g., a human) having cancer as described herein, the cancer can be any type of cancer. In some cases, a cancer can be a blood cancer. In some cases, a cancer can include one or more solid tumors. In some cases, a cancer can be a primary cancer. In some cases, a cancer can be a metastatic cancer. In some cases, a cancer can be a refractory cancer. In some cases, a cancer can be a relapsed cancer. Examples of cancers that can be treated as described herein include, without limitation, leukemias (e.g., acute lymphoblastic leukemias (ALLs), acute myeloid leukemias (AMLs), and T cell leukemias), anal cancers, astrocytomas, tetroid / rhabdoid tumors, skin cancers, biliary cancers, osteosarcomas, breast cancers, central nervous system (CNS) cancers, cervical cancers, colorectal cancers, lymphomas (e.g., T cell lymphomas), diffuse intrinsic pontine gliomas (DIPGs), endometrial cancers, esophageal cancers, ewing sarcomas, retinablastomas, gastric cancers, head and neck cancers, renal cancers, liver cancers, lung cancers, neuroblastomas, lung cancers, oral cancers, ovarian cancers, pancreatic cancers, rectal cancers, small cell lung cancers (SCLCs), non-small cell lung cancers (NSCLCs), testicular cancers, and thyroid cancers.The invention will be further described in the following examples, which do not limit the scope of the invention described in the claims.EXAMPLESExample 1: Rewiring the Spatial Mechanisms of T cell Activation to Create CAR Logic CARs stimulate T cells to kill cancer cells upon binding a chosen target antigen but also kill normal cells due to the lack of tumor specific antigens (Watanabe et al., Front Immunol 9: 2486 (2018)). Designing CARs that can recognize combinations of antigens, via Boolean logic, may make them more specific to cancer, preventing excess toxicity (Dannenfelser et al., Cell Syst 11: 215-228 e215 (2020)). Existing logic-gated designs rely on receptor co-localization (Salzer et al., Nat Commun 11:4166 (2020); and Tousley et al.,Attorney Docket No. 44807-0518WO1 / P18835-01Nature 615: 507-516 (2023)) and may place constraints on target density and geometry (Partin et al., Front Immunol 15:1304765 (2024)).This Example describes the design of logic-gated receptors that function via serial the engagement of receptors but are not dependent on transcriptional control. For example, logicgated receptors were designed that include (a) an ATPR and (b) a CAR, where the ATPR blocks antigen binding of the CAR. When the logic-gated receptor is expressed by a cell, the ATPR is free to bind its target antigen, but the CAR is blocked from binding its target antigen by the bulky ATPR (e g., by the ECD of the ATPR such as a CD45 ECD). When the ATPR binds its target antigen, the ATPR undergoes a conformational change that exposes one or more cryptic proteolysis sites within the ATPR (e.g., within the ECD of the ATPR), thus releasing the ATPR from the logic-gated receptor and generating a free CAR, where the free CAR is no longer inhibited from binding its target antigen. When the free CAR binds its target antigen, the T cell is activated. CAR T cells designed to target combinations of antigens, rather than single antigens, demonstrate greater specificity.ResultsIt was asked whether the ECD of CD45 could be re-wired to control kinase activity and T cell activation directly based on size, rather than phosphatase activity. Coupling size exclusion and antigen dependent proteolysis, these results show the development of new logic-gated receptors that function via the serial engagement of receptors on the cell surface.CD45 ECD can block CAR activityIt was evaluated whether coupling a CAR to the ECD of CD45 would prevent efficient synapse formation and potentially inhibit CAR activity simply based on steric blocking. To address this question, the activity of CD19-41BBz CARs which can potently kill NALM6 cancer cell lines at low E: T ratios and thus could serve as a sensitive read-out of CAR inhibition was inhibited, the ECD of CD45 was coupled to CARs in a couple different ways. The first design was based on a reported leucine zipper approach, where CAR and CD45 ECD were tethered intracellularly (Fig. 1 A, 45ECD-CAR-1). As this interaction was non-covalent, it was evaluated whether the dynamic on-off kinetics of leucine zippers would prevent efficient CAR inhibition. As an alternative approach, it was sought to covalentlyAttorney Docket No. 44807-0518WO1 / P18835-01couple CD45 ECD and CAR via a polypeptide linkage. Integral membrane proteins translocate in different orientations, and it is possible to express a type II transmembrane protein in series with a type I transmembrane protein. Using the type II transmembrane domain from TM1 ID, a single polypeptide was engineered where the CD45 ECD was directly coupled to a CD19-41BBz CAR (Fig. 1 A, 45ECD-CAR-2). The main difference in this design is that the CAR signaling domains are inverted relative to their native type I transmembrane orientation. Finally, as controls, equivalent designs were created without CD45 ECD to verify CAR signaling in these new formats (Fig. 1 A, CAR-1 & CAR-2).These new CARs were introduced into the TRAC locus of primary T cells using CRISPR-mediated homology directed repair while simultaneously knocking-out TRBC to prevent an allogeneic response with target cells (Fig. 6A). The CD45-CAR chimeras and corresponding controls successfully expressed and were enriched to >90% purity based on co-expressed tNGFR tag (Fig. 6B). To verify that CD45 ECD could inhibit CAR activity, CAR T cells were incubated in excess with GFP-Luciferase NALM6 cancer cell lines and measured cell growth via Incucyte live cell imaging. Both CAR-1 and CAR-2 controls potently killed NALM6 cells, but only 45ECD-CAR-2 could inhibit CAR mediated killing (Fig. IB). This result was consistent when cytotoxicity was measured using a luminescence assay across a variety of E: T ratios (Fig. 6C). A lack of significant CD69 expression in 45ECD-CAR-2 T cells co-cultured with excess NALM6 suggested that CD45 ECD could inhibit CAR signaling (Fig. 1C).To see that the inhibitory effect on CAR signaling was due to ECD size, CD45 ECD was truncated to encode only dl-d4, the rigid membrane proximal portion of CD45 ECD ~15 nm in length (Fig. ID, 45ECD-CAR-3). This is approximately the same size as the CD19 CAR immune synapse (-10-12 nm) and thus no inhibitory effect on CAR signaling was expected. 45ECD-CAR-2 and 45ECD-CAR-3 expressed similarly (Fig. 6D). When cocultured with NALM6 cells, 45ECD-CAR-3 did not inhibit CAR activity as observed by incucyte live cell imaging (Fig. IE), a luminescence assay (Fig. 6E), and via CD69 flow cytometry (Fig. IF). Collectively, these data suggested that full length CD45 ECD (CD45 RABC) could inhibit CAR binding in a size dependent manner.Attorney Docket No. 44807-0518WO1 / P18835-01Antigen Dependent CD45 proteolysis enables AND gatingIt was sought to further modify 45ECD-CAR-2 such that CD45 ECD would be proteolyzed in an antigen dependent manner. This would release a “free” CAR that could bind to a second antigen and activate the T cell, resulting in AND-gated activity via the serial engagement of receptors (Fig. 2A). Native CD45 is potentially not to a substrate of extracellular or transmembrane proteolysis in T cells. However, ECDs without canonical protease sites can be designed into synthetic intramembrane proteolysis receptors (SNIPRs) that undergo ligand-dependent proteolysis when under tension due to antigen binding. Based on these designs, it was attempted to introduce NOTCH-like behavior in 45ECD-CAR-2 by appending an scFv N-terminal to CD45 ECD and replacing the transmembrane (TMD) and juxtamembrane (JMD) domains with those from NOTCH. As NALM6 express high levels of HLA-A2, first logic-gated CAR, MANTIS- 1, was designed to kill targets that express HLA-A2 AND CD 19 (Fig. 2B and 2C). When co-cultured with a panel of isogenic lines (Fig. 7A), MANTIS-1 could more specifically kill double-target NALM6 wild-type (WT) at low E: T ratios, but still had non-specific activity against the A2 KO (CD 19+) line (Fig. 2D). This was titratable with increasing E: T ratio as measured by a luminescence readout (Fig. 7B). A lack of activity against the CD19 KO (A2+) line suggested that MANTIS-1 did not kill cells by binding via the CD45 ECD end of the receptor. This suggested that the ‘leakiness’, or killing of single target cells, was due to CAR binding.NOTCH-like MANTIS designs are leakyNOTCH proteolysis and SNIPR activation may be enhanced by T cell activation. As T cells were activate during the process of CAR engineering (Methods), it was suggested that the leakiness of MANTIS- 1 could be due to background proteolysis of CD45 ECD and release of free CAR. To better understand this, SNIPR reporter constructs were designed that expressed GFP upon proteolysis and release of an intracellular transcription factor (Fig. 8A). SNIPRs designed with a CD45 ECD hinge and an optimized SNIPR core underwent constitutive ligand independent proteolysis in primary T cells. In contrast, usage of a CD45 TMD and JMD prevented any proteolytic activity as expected based on previous reports (Fig.8B-8D). Adding modifications that prevented NOTCH TMD proteolysis or enhanced CD45Attorney Docket No. 44807-0518WO1 / P18835-01TMD proteolysis, reduced and enhanced ligand independent reporter activity respectively (Fig. 8E-8G). These data suggested that CD45 ECD could be shed from the cell surface, but in a ligand independent manner when NOTCH domains were present.It was determined whether engineering antigen-dependent activity in a CD45 ECD SNIPR format could yield more specific MANTIS CAR designs. NOTCH has a large ECD (~25 nm in length) like CD45 ECD, but NOTCH ECD proteolysis is regulated by negative regulatory domains (NRR) that prevent baseline proteolysis. Mutations and deletions in the NRR results in constitutive NOTCH activation, which is similar to what was observed with the CD45 ECD SNIPRs (SNIPR-2, Fig. 8B-8D). It was found that addition of the human or murine NOTCH1 NRR yielded ligand-dependent GFP expression (Fig. 8H-8K). These SNIPRs functioned via similar proteolytic mechanisms to native NOTCH as indicated by incubation with inhibitors of ADAM and gamma-secretase (GS) proteases (Fig. 8L).Addition of NRRs into MANTIS- 1 with modifications did not improve specificity (Fig. 9A-9C). The constitutive SI proteolysis site in the NOTCH NRR was deleted and the NOTCH TMD / JMD was replaced with that of CD45, but these modifications did not resolve toxicity to single target cells (Fig. 9D-9F). Even, more stable NRR variants either synthetic or derived from NOTCH2 did not resolve leaky activity (Fig. 9G-9I). These data suggested that optimizing antigen-dependence in SNIPR format did not translate to improved MANTIS performance.NOTCH-less MANTIS CAR optimizes precisionModifications to NOTCH domains did not improve MANTIS CAR performance so next it was determined whether removing NOTCH domains entirely may improve MANTIS CAR precision. So long as CD45 ECD is shed from the cell surface, transmembrane proteolysis is not required for efficient CAR function as was demonstrated by CAR-2 activity (Fig. 1A). The SNIPR screen revealed that CD45 ECD can be shed from the cell surface by some proteolytic mechanism with NOTCH-like transmembrane domains (Fig. 8B-8G).However, CD45 TMD / JMD were not efficient processed by gamma secretase enzymes (Fig.8B-8D). It was were unclear whether CD45 ECD could be efficiently shed upon antigenbinding when placed upstream of CD45 TMD and JMD. To test this, MANTIS-12Attorney Docket No. 44807-0518WO1 / P18835-01incorporating a CD45 TMD / JMD was expressed to see if this change inhibited antigen dependent proteolysis (Fig. 3 A and 3B). It was observed that MANTIS- 12 created ultra-precise AND-gated activity as measured by multiple metrics of cell killing and T cell activation even when incubated in excess to cancer cells (Fig. 3C-3F). Stimulating MANTIS- 1 and MANTIS- 12 in the presence of ADAM and GS inhibitors revealed that AND-gated activity was dependent on extracellular shedding and not transmembrane proteolysis (Fig. 3G). The ability of CD45 ECD to be shed from MANTIS- 12 was verified using western blot. These results suggested that NOTCH elements are not critical for antigen-dependent ECD shedding and that MANTIS-12 sheds CD45 ECD by proteolysis of cryptic ADAM sites exposed upon ligand binding.MANTIS Specificity in Mixed Cell ModelsMANTIS-12 could accurately distinguish double target from single target cells in separate wells (Fig. 2C-2F). It was sought to understand whether MANTIS- 12 could accurately distinguish double target cells from two single target cells in proximity. First, MANTIS CAR with the NALM6 CD19 were co-cultured with A2 isogenic lines mixed in the same well at equal ratios (Fig. 4A). Remarkably, MANTIS-12 cells were not activated and did not induce any cell killing unlike MANTIS- 1 and control CARs which were activated and could kill target cells and non-target cells via bystander effect (Fig. 4B-4C). This suggested that the circuit encoded by MANTIS- 12 did not prime on one cell and kill another.To see if MANTIS-12 maintained precise activity in vivo, the three NALM6 isogenic lines were injected intravenously in immunocompromised mice and treated them with a high dose of 10e6 CAR T cells (Fig. 4D, Fig. 10A-10C). CAR T cell engraftment was verified on Day 10 via flow cytometry (Fig. 10D). The mice were sacrificed 14 days after treatment to identify MANTIS specificity by looking at cells engrafted in the bone marrow and spleens. MANTIS-12 could specifically deplete double target NALM6 cells, while MANTIS-1 showed similar specificity the CD 19 CAR control (Fig. 4E-5G, Fig. 10E-10F).MANTIS Performance in Solid TumorsSolid tumors form the vast majority of cancers and cannot be targeted with conventional single target CAR T cells due to toxicity. Combinatorial antigen recognitionAttorney Docket No. 44807-0518WO1 / P18835-01can drastically improve the ability of CAR T cell therapy to fulfil this unmet need. MANTIS-12 seemed to have lower potency than standard single agent targeted CARs (Fig. 4F-4G) when tested in vivo with NALM6 target cells. The activity of MANTIS was tested in a model of A549 lung carcinoma by targeting the overexpressed antigens EGFR and HER2.Anticipating limited potency, MANTIS-13 was designed with an additional CD28 costimulation domain (FIG. 5A). Simultaneously, more potent MANTIS variations were also created by using anti-parallel NZ / CZ leucine zippers to tether additional CAR signaling domains in a type I transmembrane orientation. Three different accessory signaling modules were designed incorporating a second generation 41BBz CAR signaling domain (MANTIS-14), a third generation CD28-41BBz CAR signaling domain (MANTIS-15), and a ultrapotent MyD88CD40z signaling domain (MANTIS-16) (FIG. 5A). All of these MANTIS designs expressed successfully as measured by flow cytometry (FIG. 5B). These new MANTIS constructs were co-cultured with A549 WT (EGFR+ / HER2+) and EGFR KO A549 lines (FIG. 5C) to observe the potency and specificity of MANTIS. Most of the modifications did not improve MANTIS potency, however MANTIS- 16 could potently clear the double target cells without losing specificity to the single target EGFR KO A549 line (FIG. 5D). Tese results show how the potency of MANTIS can be adapted for solid tumor targeting without significant alteration to its specificity.Material & MethodsCAR Cloning & ConstructionCAR and SNIPR amino acids were codon optimized. CAR DNA fragments were cloned into a modified pUC19 vector backbone using the NEBuilder HiFi DNA Assembly Cloning Kit (NEB, #E5520S) according to manufacturer protocols. This pUC19 vector encoded 3’ and 5’ homology arms for TRAC knock-in, an EFla promoter, and a 2A-truncated NGFR (tNGFR, AA 1-277) tag for cell selection. Plasmid clones were sequence verified using either Sanger Sequencing or Whole Plasmid Sequencing (Plasmid-EZ, Genewiz). Amino acid sequences for CAR elements are reported in Table 1, and CAR designs are reported in Table 2. Nucleotide sequences for the TRAC homology arms and EFla promoter are provided in Table 3.Attorney Docket No. 44807-0518WO1 / P18835-01 Table 1: CAR & SNIPR Building Blocks.Attorney Docket No. 44807-0518WO1 / P18835-01Attorney Docket No. 44807-0518WO1 / P18835-01Attorney Docket No. 44807-0518WO1 / P18835-01Attorney Docket No. 44807-0518WO1 / P18835-01Table 2: Receptor Designs.Attorney Docket No. 44807-0518WO1 / P18835-01Attorney Docket No. 44807-0518WO1 / P18835-01Table 3: Additional Nucleotide Sequences.Attorney Docket No. 44807-0518WO1 / P18835-01Homology Directed Repair Template (HDRT) SynthesisSequence verified plasmids were converted into double stranded DNA homology directed repair templates via PCR using the NEB Q5 Hot Start High-Fidelity Master Mix (NEB, M0494X). For each construct, PCR reactions were pooled and purified using Ampure XP beads (Beckman Coulter Life Sciences, #A63880). In brief, 550 pL of PCR product was mixed with 140 pL of Ampure XP beads and 413 pL of 2.5 M NaCl, 20% PEG solution (Teknova, #P4137) at room temperature for 10 minutes. DNA bound to SPRI beads were collected on a magnet and washed twice with 70% ethanol. HDRTs were eluted in 25 pL nuclease free water at a concentration of 0.5-2 pg / pL, as measured by Nanodrop spectrophotometer (ThermoFisher Scientific).Target Cell LinesNALM6 cell lines virally transduced with GFP-luciferase and were cultured in RPMI-1640 (ATCC, #30-2001), 10% Fetal Bovine Serum (FBS, Gibco, # A5670701), and 1% penicillin-streptomycin (P / S, Gibco, # 15140122). To generate the HLA-A2 KO NALM6 line, NALM6 were electroporated with a CRISPR-Cas9 enzyme targeted to the HLA-A locus. Briefly, HLA-A targeted Cas9 sgRNA (GCTGCGACGTGGGGTCGGAC (SEQ ID NO 82), IDT) and Cas9 electroporation enhancer (IDT, #1075916 were resuspended at 100 pM concentration in nuclease-free duplex buffer (IDT, #11-01-03-01). CRISPR ribonucleoprotein (RNP) complex was prepared by incubating 50 pmol S.p. Cas9 Nuclease V3 (IDT, # 1081059) with 2-fold excess HLA-A sgRNA and 1.5-fold excess Cas9 electroporation enhancer for 15 minutes at room temperature. Then 5e5 NALM6 cells in 20 pL of Opti-MEM were electroporated with CRISPR RNP in a 0.1 cm cuvette (Biorad, #1652089) at 100V for 10 ms using an ECM 2001 Electro Cell Manipulator (BTX). After 7 days of recovery, residual HLA-A2 positive cells were removed from the KO mixture by bead selection with the EasySep Biotin Positive Selection Kit II (StemCell, #17683). For this protocol, a biotinylated anti-HLA-A2 antibody was used (BB7.2, Biolegend, #343322) and the non-bead bound cells were collected. CD 19 KO NALM6 were prepared in a similarAttorney Docket No. 44807-0518WO1 / P18835-01manner using a Cas9 sgRNA (CGAGGAACCTCTAGTGGTGA (SEQ ID NO: 83)). The only difference is that this polyclonal pool was prepared by mixing three single cell clones in equal ratios, rather than via bead selection. CRISPR guide RNAs are provided in Table 3.CFPAC-1 (ATCC, # CRL-1918) were cultured in IMDM (Gibco, # 12440053) supplemented with 10% FBS and 1% P / S. CFPAC-1 HLA-A2 and A3 KO lines were prepared using the same HLA-A sgRNA reported above. For incucyte studies, all CFPAC-1 lines were transduced with Incucyte NucLite Orange Lentivirus (nuclear TagRFP, Sartorius, #4771) in presence of 5 pg / mL of polybrene, and subsequently puromycin selected. For the mixed culture assays, the CFPAC-1 A2 KO line was transduced with Incucyte NucLite Green Lentivirus (nuclear GFP, Sartorius, #4624) while the A3 KO line was transduced with Incucyte NucLite NIR Lentivirus (nuclear iRFP713, Sartorius, #4805) and selected in a similar way.A549 (ATCC, #CCL-185) were cultured in F12-K medium (Gibco, # 21127022) supplemented with 10% FBS and 1% P / S. A549 EGFR KO lines were prepared by using the Cas9 sgRNA (GAGTAACAAGCTCACGCAGT (SEQ ID NO:84)) using the electroporation protocol above. EGFR KO lines were selected via flow sorting 7 days post electroporation and maintained as a polyclonal pool. For incucyte studies, all A549 lines were transduced with Incucyte NucLite Green Lentivirus (nuclear GFP, Sartorius, #4624) in the presence of 5 pg / mL of polybrene, and subsequently puromycin selected.T cell Culture & EngineeringPrimary human T cells were derived from commercially available leukapheresis products (StemCell Technologies & AllCells). Peripheral blood mononuclear cells (PBMCs) were purified from apheresis products using density gradient centrifugation either with Ficoll Paque Plus (Cytiva, #17144002) or Lymphoprep (StemCell Technologies, #18060) in SepMate PBMC isolation tubes (StemCell Technologies, #85450). Isolated PBMCs were cryopreserved in 90% FBS, 10% DMSO and kept in liquid nitrogen cold storage.T cells were engineered. Two days prior to CAR engineering, T cells were isolated from frozen PBMCs via immunomagnetic isolation using the EasySep Human T cell Isolation Kit (StemCell Technologies, #17951) and then stimulated with CD3 / CD28Attorney Docket No. 44807-0518WO1 / P18835-01Dynabeads (Gibco, #1113 ID) in a 1:1 ratio in T cell media which comprised RPMI-1640 supplemented with 10% FBS, 1% P / S, recombinant human IL-2 (100 lU / mL, Proleukin, Prometheus Laboratories), and recombinant human IL-7 (5 ng / mL, Biolegend, #581908) for 48-56 hours. Following CD3 / CD28 stimulation, Dynabeads were removed from activated T cells using a magnet and rested at room temperature. During this time, the electroporation substrate was prepared. Every le6 T cells were electroporated with 25 pmol of TRAC targeting A.s. Casl2a Ultra (Cpfl, IDT, #10001273) RNP, TRBC targeting RNP, and 500 ng of HDRT. TRAC and TRBC RNP master mixes were prepared in separate tubes with the molar ratios listed above except with Cpfl enzyme and Cpfl electroporation enhancer (IDT, #1076301). After incubation at room temperature for 15 minutes, TRAC and TRBC RNPs were mixed in a 1:1 molar ratio. Immediately prior to electroporation, T cells were centrifuged at 90xg for 10 minutes and then resuspended in P3 buffer (Lonza, #V4XP-3034) at a density of 50e6 cells / mL. For a typical experiment, 5e6 T cells in 100 pL P3 buffer were mixed with 12.75 pL TRAC / TRBC RNP, and 2.5 pg of HDRT diluted in 10 pL in duplex buffer. 110 pL of this mixture was transferred into a 100 pL cuvette and electroporated using the pulse code EO-115 on the Lonza 4D Nucleofector X-Unit (Lonza, AAF-1003X). After electroporation, T cells were rested at room temperature for 5 minutes, after which 500 uL of warm RPMI-1640 (no cytokines) was added, and the T cells were rested for an additional 60 minutes in the tissue culture incubator. T cells were then maintained at ~1-L5e6 cells / mL in T cell media and the media was exchanged every 2-3 days. On day 4-8 post electroporation, engineered T cells were enriched using via NGFR bead selection with the EasySep Release Human PSC-Derived Neural Crest Cell Positive Selection Kit (StemCell Technologies, #100-0047). T cells were used in killing assays 10 days after electroporation, and receptor expression and cell purity was assessed via flow cytometry within 24 before experimentation. CRISPR guide RNAs are provided in Table 3.Flow CytometryCells were briefly washed and resuspended in PBS by centrifugation and aspirating the supernatant. Cell staining was performed at room temperature, except for in vivo samples which were stained on ice. Prior to antibody staining, cells were stained with LIVE / DEADAttorney Docket No. 44807-0518WO1 / P18835-01Fixable Near-IR Dead Cell Stain (1 pL / 100 pL / le6 cells; Invitrogen, # L34976) in PBS at room temperature for 10 minutes. Then cells were washed twice in flow staining buffer, which comprised of PBS supplemented with 0.5% bovine serum albumin, 2 mM EDTA, and 0.1% sodium azide. If needed, Fc receptors were first blocked using TruStain FcX PLUS (Biolegend, #156604) and / or Human TruStain FcX (Biolegend, #422302) in 50 pL of flow staining buffer for 10 minutes. Then the desired antibody cocktails were added for 25 minutes for staining in the dark in flow staining buffer. When antibodies with multiple brilliant violet dyes were used, the BD Horizon Brilliant Stain Buffer (BD Biosciences, #566349) was used. After staining, cells were washed twice with flow staining buffer and samples were run on the Attune NxT flow cytometer (ThermoFisher Scientific). Spectral compensation was conducted using the AbC Total Antibody Compensation Bead Kit (Invitrogen, #A10497) and the ArC Amine Reactive Compensation Bead Kit (Invitrogen, #A10346). Flow data was plotted using FloJo (BD Biosciences, vl0.9.0), but spectral compensation was applied to flow data on the Attune NxT Flow Cytometer Software (ThermoFisher Scientific, v6.2.1).T cell Co-Culture AssaysEngineered T cells were incubated with target cells in the amounts and durations listed in the figure legends. Co-cultures with an incucyte or flow cytometry readout (CD69 flow, SNIPR activation assays, mixed co-culture killing) were setup in 200 pL cytokine free RPMI-1640 medium in 96 well flat bottom plates (Corning, #3595). Flow cytometry was conducted as mentioned above. Interferon gamma from co-cultures was assessed by aspirating 100 uL of the co-culture supernatant and assaying with the Human IFN-gamma ELISA kit (R& D Systems, #DIF50C) according to manufacturer recommended protocols. Live cell imaging of co-cultures was performed with Incucyte SX5 imaging system (Sartorius). For incucyte assays, target cells were pre-plated atleast 30 minutes prior to T cell addition. When non-adherent NALM6 target cells were used, the 96 well plates were coated with 50 pL of 0.1 mg / mL poly-D-lysine (Gibco, #A3890401) solution at room temperature for 60 minutes. The well was then briefly rinsed with 100 pL of sterile water, and then air dried for 60 minutes prior to target cell addition. When cell killing was addressed by aAttorney Docket No. 44807-0518WO1 / P18835-01luminescence readout, co-cultures were prepared in 100 pL of cytokine free RPMI-1640 in opaque 96-well flat bottom plates (ThermoFisher Scientific, # 136102). After the culture period, relative target cell viability was assessed using the Steady Gio Luciferase Assay System (Promega, #E2510) using the manufacturer recommended protocols. Luminescence was quantified using the Synergy Hl microplate reader (Biotek) with the Gen5 software (Biotek, v2.07).Animal Experiments6-12-week-old female lAOT). Cs,-PrkdcscldIl2r^mIWjlI E] (NSG) mice were housed in 50% humidity at 70-75°F in a 12-hour light / dark cycle.For the mixed NALM6 target cell model, 100k NALM6 WT (A2+ / CD19+), 100k NALM6 A2 KO (CD 19+), and 400k NALM9 CD 19 KO (A2+) cell lines were inj ected via tail vein in 200 pL of PBS. More NALM6 CD19 KO cells were injected because these cells grow slower and engrafted less efficiently in a previous pilot experiment where an equal number of all cells were injected. 3 days after target cell injected, mice were randomized into different groups prior to treatment. 10e6 CAR or MANTIS CAR T cells were injected via tail vein with all cells being normalized 90% NGFR positivity (1 l.le6 total T cells). Cells were diluted to this editing rate by diluting with TCR KO cells. For the TCR KO control, 11. Ie6 total T cells were injected. The experimenter was blinded to the groups. On day 10 after T cell injection, 100 pL of blood was collected via submandibular vein bleed into EDTA-treated tubes (Sarstedt, #NC9299309). Red blood cells were then lysed with Ack Lysing buffer (Quality Biological, #118-156-101), and then cells were stained using the flow cytometry methods reported above. On day 14, mice were sacrificed and the spleens and left femurs were dissected from the mice. To extract the bone marrow, femurs were aspirated with 10 mL of PBS with a 25G syringe into a 70 pL cell strainer (Celltreat, #229483).Spleens and bone marrow aspirate were converted into a single cell suspension by mashing with a pestle (Celltreat, #229480) into the cell strainer and rinsing with 10 mL of PBS.Samples were then processed in a similar fashion to peripheral blood samples. Due to large sample quantity, only 10% of the total splenocyte volume was sampled. To quantify the number of engrafted cells and normalize across different sample sizes, it was assumed that TAttorney Docket No. 44807-0518WO1 / P18835-01cell and / or target cell engraftment did not affect the survival of normal murine CD45+ cells in the tissues of interest. Thus, the count of each cell type was normalized based on the murine CD45+ count. To make this adjustment, each target cell count was simply multiped by the scaling factor defined as:is the scaling factor for sample, andsf‘ is the mean murine Xi i FL0ORQ CD45+ count across all samples, and is the murine CD45 count in sample. The function rounds down the mean murine CD45+ count across all samples to the nearest le5. The mean number of events sampled was ~5e5 for bone marrow samples and ~le5 forsplenocytes. Based on this scaling factor, the adjusted target cell count ( ’ ) can be calculated from the observed target cell countas:Statistical Analysis & PlottingStatistical analysis was performed with Prism vlO.2.1 (Graphpad). The statistical test that was used for each analysis is indicated in the figure legends. Some plots were generated using Prism v5.00 (Graphpad). All graphics were generated in house with protein structures rendered via ChimeraX (UCSF, vl.8) and then converted into bitmap vector images with Inkscape (vl.4).Example 2: Rewiring the Spatial Mechanisms ofT cell Activation to Create CAR Logic The results in this Example re-present and expand on at least some of the results provided in other Examples. Unless otherwise specified, methods and materials were as described in Example 1.Attorney Docket No. 44807-0518WO1 / P18835-01Materials and MethodsCAR Cloning & ConstructionAmino acid sequences for CAR elements are reported in Table 1 and Table 4, and CAR designs are reported in Table 2 and Table 5. Nucleotide sequences for the TRAC homology arms and EFla promoter are provided in Table 3 and Table 6.Table 4. CAR & SNIPR Building Blocks.Attorney Docket No. 44807-0518WO1 / P18835-01Table 5. Receptor Designs.Attorney Docket No. 44807-0518WO1 / P18835-01Table 6. Additional Nucleotide Sequences.T cell Culture & EngineeringJurkat T cells engineered to express MANTIS receptors were engineered in a similar way to primary T cells, except that the Jurkat T cells were not bead activated. The electroporation process was kept the same except that 3-5e6 Jurkat cells resuspended in 100Attorney Docket No. 44807-0518WO1 / P18835-01pL of Lonza SE Buffer (Lonza, #VXC-1024) and electroporated with pulse code CL-120. All CRISPR guide RNAs are consolidated in Table 3 and Table 6.Target Cell Line GenerationSKOV3 (ATCC, #HTB-77) were cultured in McCoy’s 5a (Gibco, #16600082) supplemented with 10% FBS and 1% PS. SKOV3-Luc cells were used for in vivo studies (Cellomics, #SC-1555). For incucyte studies, SKOV3 lines were transduced with Incucyte NucLite Green Lentivirus (nuclear GFP, Sartorius, #4624) in the presence of 5 pg / mL of polybrene, and subsequently puromycin selected. The NucLite GFP SKOV3 was used as the parent cell line for producing EGFR and HER2 KOs. For knocking out EGFR, a cocktail of 3 guide RNAs was used (Hs. Cas9. EGFR.l. AA: TGCTGACTATGTCCCGCCAC (SEQ ID NO 141), Hs Cas9. EGFR 1 AB: CCTTGCACGTGGCTTCGTCT (SEQ IDNO:142), and Hs. Cas9. EGFR.l. AC: GAGTAACAAGCTCACGCAGT (SEQ IDNO:84)). For knock-out HER2, a cocktail of 3 guide RNAs was used: (Hs. Cas9. ERBB2.1. AA:CAACTACCTTTCTACGGACG (SEQ ID NO: 143), Hs. Cas9. ERBB2.1 AB:GCCCTTACACATCGGAGAAC (SEQ ID NO: 144), Hs. Cas9. ERBB2.1. AC:GATAGACACCAACCGCTCTC (SEQ ID NO: 145)). For knock-out, le6 SKOV3 cells resuspended in 100 pL of Lonza SF Buffer (Lonza, #V4XC-2024) were electroporated with 50 pmol of each Cas9 RNP (150 pmol total RNP) prepared as above with pulse code FE-132 on the Lonza 4D Nucleofector X-Unit (Lonza, AAF-1003X). After electroporation, the cells were rested for 5 minutes at room temperature, and then 500 uL of media was added and the cells were rested for an additional 20 minutes in the incubator. The cells were then recovered in a T75 flask. KO efficiency was verified by flow cytometry and target null cell lines were isolated via the modified Biotin selection reported above. HER2 KOs were enriched using a biotinylated anti-Her2 antibody (Biotechne, # FAB9589B) and EGFR KOs were enriched using a biotinylated anti-EGFR antibody (Biolegend, #352934). Following enrichment, cells were single cell cloned, and individual clones were used for all in vitro experiments. Single cell clones were verified via flow staining and sequencing. A complete EGFR KO line could be generated, but a complete HER2 KO line could not be readily generated possibly due to high dependency of SKOV3 on HER2 (Tsherniak et al., Cell 170:564-576 e516 (2017); andAttorney Docket No. 44807-0518WO1 / P18835-01Montero et al., Oncotarget, 6:30057-30071 (2015)). The SKOV3 HER2 pKO line contained two functional alleles with in-frame deletions and the cell line had very low HER2 expression.GFP-Luciferized Jurkat Clone E6-1 (ATCC, TIB-152) cells were cultured in RPMI- 1640 supplemented with 10% FBS and 1% PS. To overexpress EGFR in Jurkat cells, le6 Jurkat cells were transduced with Human EGFR Lentivirus (G& P Biosciences, #LTV0169) in presence of 8 ug / mL of polybrene overnight. The following day, cells were removed from transduction recovered for 1 week. EGFR positive cells enriched using the EasySep Biotin Positive Selection Kit II (StemCell, #17683) with a biotinylated anti-EGFR antibody (Biolegend, #352934). To create Jurkat cells overexpressing HER2, a truncated variant of HER2 (AA1-684) was knocked-into the TRAC locus of using the same approach described above. These cells were also enriched using EasySep Biotin Positive Selection Kit II (StemCell, #17683) except with a biotinylated anti-Her2 antibody (Biotechne, # FAB9589B). Jurkat cells expressing EGFR and HER2 were prepared the same way, except the truncated HER2 gene was knocked into TRAC locus of the enriched Jurkat EGFR pool. An EGFR+ / HER2+ single cell clone was used in vivo experiments. CRISPR guide RNAs and truncated HER2 knock-in sequence are consolidated in Supplementary Table 3.ResultsNOTCH-less MANTIS receptor optimizes precisionAs described in Example 1, MANTIS-12 incorporating a CD45 TMD / JMD in place of SNIPR domains was expressed (Fig. 3A-3B), and it was observed that MANTIS-12 created ultra-precise AND-gated activity as measured by multiple metrics of cell killing and T cell activation even when incubated in excess to cancer cells (Fig. 3C-3F). Also as described in Example 1, stimulating MANTIS-1 and MANTIS-12 in the presence of ADAM and GS inhibitors revealed that AND-gated activity was partially dependent on extracellular shedding and not transmembrane proteolysis (Fig. 3G).The ability of CD45 ECD to be shed from MANTIS-12 expressed in Jurkat cells in response to anti-c-myc stimulation was also verified (Fig. 12). This suggested that CD45 ECD proteolysis depended only on binding via the N-terminus of MANTIS. Collectively,Attorney Docket No. 44807-0518WO1 / P18835-01these results suggested that NOTCH elements are not critical for antigen-dependent ECD shedding and that MANTIS-12 sheds CD45 ECD by proteolysis of cryptic sites exposed upon ligand binding.Optimizing MANTIS for Solid Tumor PerformanceCAR T cells targeted to several solid tumor antigens have yielded severe on-target off-tumor toxicities (Larners et al., J. Clin. Oncol., 24:e20-22 (2006); Morgan et al., Mol. Ther., 18:843-851 (2010); Haas et al., Mol. Ther., 31:2309-2325 (2023); and Thistlethwaite et al., Cancer Immunol. Immunother., 66:1425-1436 (2017)) and logic-gated CAR T cells can overcome this barrier producing effective therapies. Recently, similar toxicities were modeled pre-clinically in mice with CAR T cells directed by a cross-reactive anti-human / mouse HER2 DARPin (H10-2-G3) (Hammill et al., Mol. Ther. Oncolytics, 17:278-292 (2020); and Piraner et al., Nature, 638:805-813 (2025)).These experiments describe how MANTIS can overcome on-target off-tumor toxicity.SKOV3 was picked as a model cell line given its high expression of HER2 and reactivity to anti-HER2 CAR T cells. SKOV3 cells also express high amounts of EGFR, thus EGFR 4A79 HER2 was chose as a model antigen pair. To address receptor specificity, EGFR KO and HER2 partial KO (pKO) variants of SKOV3 were engineered (Fig. 13 A). A complete HER2 KO could not be generated possibly due to the high dependency of SKOV3 on HER2 for survival.In prior reports, lung toxicity in mice was better potentiated by DARPin CARs with CD28 co-stimulation (Hammill et al., Mol. Ther. Oncolytics, 17:278-292 (2020)). Thus, MANTIS- 12 was modified to contain CD28 co-stimulation and re-targeted the receptor to EGFRTEVD HER2, creating MANTIS- 13 (Fig. 13B). All constructs and controls successfully expressed in primary T cells (Fig. 13B-13C). In co-culture, MANTIS-13 more potently killed the double-target SKOV3 WT cells than other lines at a 5:1 E: T ratio. However, SKOV3 WT killing was not complete and MANTIS- 13 also had subtle reactivity to the HER2 pKO line. To further investigate leakiness, EGFR and HER2 were overexpressed in Jurkat cells which naturally do not express these proteins (Fig. 13E). Co-culture with these lines revealed thatAttorney Docket No. 44807-0518WO1 / P18835-01MANTIS-13 could kill EGFR overexpressing Jurkat cells (Fig. 13F-13G). Collectively, this suggested that MANTIS- 13 could be stimulated by independent binding of the anti -EGFR scFv on the CD45-ECD domain. This was contrary to CAR-mediated leakiness observed with MANTIS- 1, and thus, it was sought to further optimize MANTIS-13.Regarding potency, the CAR portion of MANTIS was modified to contain a MyD88-CD40 (MC) co-stimulation domain to improve the potency of engineered T cells (Mog et al., Sci. Transl. Med., 16:eadg7123 (2024)). Alongside MC, an additional CD3z signaling domain was added in the type I orientation by using a pair of anti-parallel leucine zippers (Fig. 14A) since the non-native type II orientation in MANTIS could potentially impair efficient signaling. Adding this accessory signaling domain slightly decreased CAR expression (HER2CAR-MC, Fig. 14B), but it dramatically improved CAR potency (Fig. 14C-14D).Regarding specificity, previous reports had suggested that elongated immune synapses could signal efficiently given a high affinity TCR-ligand interaction (Chen et al., Front. Immunol., 8:793 (2017); and Al-Aghbar et al., Front. Immunol., 9:713 (2018)). This suggested that MANTIS receptors engineered with high affinity N-terminal binders may result in non-specific T cell activation. MANTIS-12 retained high precision and the use of a moderate affinity N-terminal scFv (BB7.2, 162 nM) may support this hypothesis. MANTIS-MC was created and the anti -EGFR scFv was exchanged with variants derived from the CIO antibody clone with different affinity levels. In these experiments, the human-specific 4D5 scFv was used as the anti-HER2 binder. The new MANTIS receptors (MANTIS 17-20, Fig.14E-14F) were co-cultured with the engineered Jurkat lines because they were more sensitive to killing. Remarkably, MANTIS variants with lower affinity N-terminal binders had higher specificity, with the lowest affinity variant (MANTIS-20) having near perfect precision (Fig.14G-14H).MANTIS Performance in a Model of On-Target Off-Tumor Toxicity4D5 in MANTIS 17 and 20 was then exchanged back to the H10-2-G3 DARPin to study effects on safety and efficacy (MANTIS 16 and 21, Fig. 11A-1 IB). As a benchmark, the most up-to-date AND gated receptor, LINK CAR, was also expressed to target EGFR andAttorney Docket No. 44807-0518WO1 / P18835-01HER2 (Fig. 11 A-l IB). All MANTIS variants could completely clear SKOV3 WT cells in vitro, and the lower affinity MANTIS-21 variant retained perfect AND-gated precision (Fig.11C-1 ID) as previously observed (Fig. 14E-14F). On the other hand, LINK CAR could not mediate any SKOV3 lysis at a 5:1 E: T ratio (Fig. 11C-1 ID), possibly due to the lack of additional co-stimulation. However, LINK CAR could mediate target lysis of Jurkat cells overexpressing EGFR and HER2 (Fig. 15A-15C), but also had some leaky activity based on the LAT component of the receptor (Fig. 15B-15C). Thus, additional co-stimulation of LINK CAR may also potentiate greater leakiness.Seeing the high potency and specificity of MANTIS-21 in vitro, this construct was tested in in vivo models of HER2 on-target off-tumor toxicity (Fig. 1 IE). First, SKOV3 luciferase expressing cells (SKOV3-luc) were orthotopically implanted intraperitoneally (i.p.) in immunodeficient mice and tumor engraftment was verified. After randomization, all mice were treated with an i.p. infusion of CAR T cells (Fig. 16A). Following administration, HER2CAR-MC and MANTIS-21 T cells rapidly induced tumor regression (Fig. 11F-11G). All CAR T cells entered systemic circulation by Day 10 post i.p. injection, but only HER2CAR-MC cells were expanding by day 31 post infusion (Fig. 11H). By day 20-23, HER2CAR-MC treated mice developed progressively worsening edema involving hind legs, tail, and face resulting in weight gain (Fig. 1 II). Remarkably, 4 / 5 MANTIS-21 treated mice demonstrated no signs of toxicity and extended survival (Fig. 11 J).Example 3: Exemplary SNIPR SequencesThis Example provides sequences of exemplary SNIPR molecules.SNIPR- 1 DesignCD8a SP - myc tag - BB7.2 - tCD8a Hinge - NOTCH1 TMD - NOTCH2 JMD - Gal4DBD_VP64 TF - E2A - tNGFRAmino Acid Sequence for SNIPR-1 MALPVTALLLPLALLLHAARPEQKLISEEDLQVQLQQSGPELVKPGASVKMSCKASGYTFTSYHIQWV KQRPGQGLEWIGWIYPGDGSTQYNEKFKGKTTLTADKSSSTAYMLLSSLTSEDSAIYFCAREGTYYAM DYWGQGTSVTVSSGGGGSGGGGSGGGGSDIVMTQAPLSLPVSLGDQVSISCRSSQSIVHSNGNTYLEW YLQKPGQSPKLLIYKVSNRFSGVPDRFSGSGSGTDFTLKISRVEAEDLGVYYCFQGSHVPRTFGGGTKAttorney Docket No. 44807-0518WO1 / P18835-01LELKRTTTTPAPRPPTPAPTIASQPLSLRPEACFMYVAAAAFVLLFFVGCGVLLSKRKRKHMKLLSSI EQACDICRLKKLKCSKEKPKCAKCLKNNWECRYSPKTKRSPLTRAHLTEVESRLERLEQLFLLIFPRE DLDMILKMDSLQDIKALLTGLFVQDNVNKDAVTDRLASVETDMPLTLRQHRISATSSSEESSNKGQRQ LTVSAAAGGSGGSGGSDALDDFDLDMLGSDALDDFDLDMLGSDALDDFDLDMLGSDALDDFDLDMLGS RAKRSGSGQCTNYALLKLAGDVESNPGPMGAGATGRAMDGPRLLLLLLLGVSLGGAKEACPTGLYTHS GECCKACNLGEGVAQPCGANQTVCEPCLDSVTFSDVVSATEPCKPCTECVGLQSMSAPCVEADDAVCR CAYGYYQDETTGRCEACRVCEAGSGLVFSCQDKQNTVCEECPDGTYSDEANHVDPCLPCTVCEDTERQ LRECTRWADAECEEIPGRWITRSTPPEGSDSTAPSTQEPEAPPEQDLIASTVAGVVTTVMGSSQPVVTNucleic Acid Sequence for SNIPR-1 ATGGCTCTGCCTGTGACAGCTCTGCTGCTGCCTCTGGCTCTGCTTCTGCATGCCGCTAGACCTGAGCA GAAGCTGATCTCCGAAGAGGACCTGCAGGTTCAGCTGCAGCAGTCTGGACCTGAGCTGGTTAAGCCTG GCGCTTCCGTGAAGATGAGCTGCAAGGCCAGCGGCTACACCTTCACCAGCTACCACATCCAGTGGGTC AAGCAGAGGCCTGGACAGGGACTCGAGTGGATCGGCTGGATCTATCCTGGCGACGGCAGCACCCAGTA CAACGAGAAGTTCAAGGGCAAGACCACACTGACCGCCGACAAGAGCAGCAGCACAGCCTACATGCTGC TGAGCAGCCTGACCAGCGAGGACAGCGCCATCTACTTTTGTGCCAGAGAGGGCACCTACTACGCCATG GATTATTGGGGCCAGGGCACCAGCGTGACAGTCTCTTCTGGTGGCGGAGGATCTGGCGGAGGTGGAAG CGGCGGAGGCGGATCTGATATCGTGATGACACAGGCCCCTCTGAGCCTGCCTGTGTCTCTGGGAGATC AGGTGTCCATCAGCTGTCGGAGCAGCCAGAGCATCGTGCACAGCAACGGCAACACCTACCTGGAATGG TATCTGCAGAAGCCCGGACAGAGCCCCAAGCTGCTGATCTACAAGGTGTCCAACCGGTTCAGCGGCGT GCCCGATAGATTTTCTGGCTCTGGCAGCGGCACCGACTTCACCCTGAAGATCTCTAGAGTGGAAGCCG AGGACCTGGGCGTGTACTACTGCTTCCAAGGCAGCCACGTGCCAAGAACCTTTGGCGGCGGAACAAAG CTGGAACTGAAGCGGACAACCACCACACCAGCTCCTAGACCTCCAACTCCTGCTCCTACAATCGCCAG CCAGCCTCTGTCTCTGAGGCCCGAGGCCTGCTTTATGTACGTGGCCGCTGCTGCCTTCGTGCTGCTGT TCTTTGTTGGCTGCGGAGTGCTGCTGAGCAAGCGGAAGAGAAAGCACATGAAGCTGCTGAGCAGCATC GAGCAGGCCTGTGACATCTGCCGGCTGAAGAAACTGAAGTGCAGCAAAGAAAAGCCCAAGTGCGCCAA GTGCCTGAAGAACAACTGGGAGTGCCGGTACAGCCCCAAGACCAAGAGAAGCCCTCTGACAAGAGCCC ACCTGACCGAGGTGGAAAGCCGGCTGGAAAGACTCGAGCAGCTGTTCCTGCTGATCTTCCCCAGAGAA GATCTGGACATGATCCTGAAGATGGACAGCCTGCAGGACATCAAGGCCCTGCTGACCGGACTGTTCGT GCAGGACAACGTGAACAAGGACGCCGTGACCGATAGACTGGCCAGCGTGGAAACCGACATGCCCCTGA CACTGCGGCAGCACAGAATCAGCGCCACAAGCAGCAGCGAGGAAAGCAGCAACAAGGGCCAGAGACAG CTGACAGTGTCTGCTGCTGCTGGCGGAAGCGGAGGATCTGGTGGATCTGATGCCCTGGACGACTTCGA CCTGGATATGCTGGGCAGCGACGCCCTGGATGATTTCGATCTCGACATGCTCGGCTCCGACGCTCTCG ACGACTTTGATTTGGACATGTTGGGCTCCGATGCACTTGATGATTTTGACTTGGATATGCTCGGAAGC CGGGCCAAACGATCTGGCTCTGGCCAGTGTACCAACTATGCCCTGCTCAAGCTCGCTGGCGACGTCGA GTCTAACCCTGGACCAATGGGAGCTGGCGCTACAGGCAGAGCTATGGATGGACCTAGACTGCTGCTGC TCCTGCTTCTGGGAGTGTCTCTTGGCGGAGCCAAAGAGGCCTGTCCTACCGGCCTGTATACACACTCT GGCGAGTGCTGCAAGGCCTGCAATCTTGGAGAAGGCGTCGCACAGCCTTGCGGCGCTAATCAGACAGT GTGCGAGCCTTGCCTGGACAGCGTGACCTTTAGCGACGTGGTGTCAGCCACCGAGCCATGCAAGCCAT GTACCGAGTGTGTGGGCCTGCAGAGCATGTCTGCCCCTTGCGTGGAAGCTGACGATGCCGTGTGTAGA TGCGCCTACGGCTACTACCAGGACGAGACAACAGGCAGATGCGAGGCCTGTAGAGTGTGCGAAGCTGG ATCTGGCCTGGTGTTCAGCTGCCAAGACAAGCAGAACACCGTGTGCGAGGAATGCCCCGATGGCACCT ATAGCGACGAGGCCAACCATGTGGATCCCTGCCTGCCTTGTACCGTGTGTGAAGATACCGAGCGGCAG CTGCGCGAGTGTACAAGATGGGCTGATGCCGAGTGCGAAGAGATCCCTGGCAGATGGATCACCAGAAG CACACCTCCAGAGGGCAGCGATAGCACAGCCCCTTCTACACAAGAGCCCGAGGCTCCTCCTGAGCAGG ACCTGATTGCTTCTACAGTGGCTGGCGTCGTGACCACCGTGATGGGATCTAGTCAGCCCGTGGTCACCAttorney Docket No. 44807-0518WO1 / P18835-01AGAGGCACCACCGACAATCTGATCCCCGTGTACTGTAGCATCCTGGCCGCCGTGGTTGTTGGACTGGT GGCCTATATCGCCTTCAAGCGGTGGAACAGCTGA(SEQ ID NO:92)SNIPR-2 DesignCD8a SP - myc tag - BB7.2 - CD45 ECD - NOTCH1 TMD - NOTCH2 JMD - Gal4DBD_VP64 TF -E2A - tNGFRAmino Acid Sequence for SNIPR-2 MALPVTALLLPLALLLHAARPEQKLISEEDLQVQLQQSGPELVKPGASVKMSCKASGYTFTSYHIQWV KQRPGQGLEWIGWIYPGDGSTQYNEKFKGKTTLTADKSSSTAYMLLSSLTSEDSAIYFCAREGTYYAM DYWGQGTSVTVSSGGGGSGGGGSGGGGSDIVMTQAPLSLPVSLGDQVSISCRSSQSIVHSNGNTYLEW YLQKPGQSPKLLIYKVSNRFSGVPDRFSGSGSGTDFTLKISRVEAEDLGVYYCFQGSHVPRT FGGGTK LELKRTQSPTPSPTGLTTAKMPSVPLSSDPLPTHTTAFSPASTFERENDFSETTTSLSPDNTSTQVSP DSLDNASAFNTTGVSSVQTPHLPTHADSQTPSAGTDTQTFSGSAANAKLNPTPGSNAISDVPGERSTA STFPTDPVSPLTTTLSLAHHSSAALPARTSNTTITANTSDAYLNASETTTLSPSGSAVISTTTIATTP SKPTCDEKYANITVDYLYNKETKLFTAKLNVNENVECGNNTCTNNEVHNLTECKNASVSISHNSCTAP DKTLILDVPPGVEKFQLHDCTQVEKADTTICLKWKNIETFTCDTQNITYRFQCGNMIFDNKEIKLENL EPEHEYKCDSEILYNNHKFTNASKIIKTDFGSPGEPQIIFCRSEAAHQGVITWNPPQRSFHNFTLCYI KETEKDCLNLDKNLIKYDLQNLKPYTKYVLSLHAYIIAKVQRNGSAAMCHFTTKSAPPSQVWNMTVSM TSDNSMHVKCRPPRDRNGPHERYHLEVEAGNTLVRNESHKNCDFRVKDLQYSTDYTFKAYFHNGDYPG EPFILHHSTSYNSKFMYVAAAAFVLLFFVGCGVLLSKRKRKHMKLLSSIEQACDICRLKKLKCSKEKP KCAKCLKNNWECRYSPKTKRSPLTRAHLTEVESRLERLEQLFLLIFPREDLDMILKMDSLQDIKALLT GLFVQDNVNKDAVTDRLASVETDMPLTLRQHRISATSSSEESSNKGQRQLTVSAAAGGSGGSGGSDAL DDFDLDMLGSDALDDFDLDMLGSDALDDFDLDMLGSDALDDFDLDMLGSRAKRSGSGQCTNYALLKLA GDVESNPGPMGAGATGRAMDGPRLLLLLLLGVSLGGAKEACPTGLYTHSGECCKACNLGEGVAQPCGA NQTVCEPCLDSVTFSDVVSATEPCKPCTECVGLQSMSAPCVEADDAVCRCAYGYYQDETTGRCEACRV CEAGSGLVFSCQDKQNTVCEECPDGTYSDEANHVDPCLPCTVCEDTERQLRECTRWADAECEEIPGRW ITRSTPPEGSDSTAPSTQEPEAPPEQDLIASTVAGVVTTVMGSSQPVVTRGTTDNLIPVYCSILAAVV VGLVAY IAFKRWNS *(SEQ ID NO:93)Nucleic Acid Sequence for SNIPR-2 ATGGCTCTGCCTGTGACAGCTCTGCTGCTGCCTCTGGCTCTGCTTCTGCATGCCGCTAGACCTGAGCA GAAGCTGATCTCCGAAGAGGACCTGCAGGTTCAGCTGCAGCAGTCTGGACCTGAGCTGGTTAAGCCTG GCGCTTCCGTGAAGATGAGCTGCAAGGCCAGCGGCTACACCTTCACCAGCTACCACATCCAGTGGGTC AAGCAGAGGCCTGGACAGGGACTCGAGTGGATCGGCTGGATCTATCCTGGCGACGGCAGCACCCAGTA CAACGAGAAGTTCAAGGGCAAGACCACACTGACCGCCGACAAGAGCAGCAGCACAGCCTACATGCTGC TGAGCAGCCTGACCAGCGAGGACAGCGCCATCTACTTTTGTGCCAGAGAGGGCACCTACTACGCCATG GATTATTGGGGCCAGGGCACCAGCGTGACAGTCTCTTCTGGTGGCGGAGGATCTGGCGGAGGTGGAAG CGGCGGAGGCGGATCTGATATCGTGATGACACAGGCCCCTCTGAGCCTGCCTGTGTCTCTGGGAGATC AGGTGTCCATCAGCTGTCGGAGCAGCCAGAGCATCGTGCACAGCAACGGCAACACCTACCTGGAATGG TATCTGCAGAAGCCCGGACAGAGCCCCAAGCTGCTGATCTACAAGGTGTCCAACCGGTTCAGCGGCGT GCCCGATAGATTTTCTGGCTCTGGCAGCGGCACCGACTTCACCCTGAAGATCTCTAGAGTGGAAGCCG AGGACCTGGGCGTGTACTACTGCTTCCAAGGCAGCCACGTGCCAAGAACCTTTGGCGGCGGAACAAAG CTGGAACTGAAGCGGACACAGAGCCCCACACCATCTCCAACAGGACTGACCACCGCCAAGATGCCTAGAttorney Docket No. 44807-0518WO1 / P18835-01CGTGCCCCTCTCTTCTGACCCTCTGCCTACACACACCACCGCTTTTAGCCCTGCCAGCACCTTCGAGA GAGAGAACGACTTCAGCGAGACAACCACCTCTCTGAGCCCCGACAACACCAGCACACAGGTGTCCCCA GACAGCCTGGATAATGCCAGCGCCTTCAATACCACCGGCGTGTCCTCTGTGCAGACCCCTCATCTGCC AACACACGCCGATAGCCAGACACCTTCTGCCGGCACCGATACACAGACCTTTTCTGGCTCTGCCGCCA ACGCCAAGCTGAACCCTACACCTGGCAGCAACGCCATCTCTGATGTGCCTGGCGAGAGAAGCACCGCC AGCACATTTCCAACAGACCCCGTGTCTCCCCTGACCACCACACTGTCTCTGGCCCACCATAGCTCTGC TGCCCTGCCTGCCAGAACCAGCAACACCACCATCACCGCCAATACCAGCGACGCCTACCTGAACGCCA GCGAAACCACAACACTGAGCCCTAGCGGAAGCGCCGTGATCAGCACAACCACAATCGCCACCACACCT AGCAAGCCTACCTGCGACGAGAAGTACGCCAACATCACCGTGGACTACCTGTACAACAAAGAGACAAA GCTGTTCACGGCCAAGCTCAACGTGAACGAGAACGTGGAATGCGGCAACAATACCTGCACCAACAACG AGGTGCACAACCTGACCGAGTGCAAGAACGCCTCCGTGTCCATCAGCCACAACAGCTGCACAGCCCCT GACAAGACCCTGATCCTGGATGTGCCTCCTGGCGTGGAAAAGTTCCAGCTGCACGATTGCACCCAGGT GGAAAAGGCCGATACCACCATCTGCCTGAAGTGGAAGAACATCGAGACATTCACCTGTGACACCCAGA ACATCACCTACCGGTTCCAGTGCGGCAATATGATCTTCGATAACAAAGAAATCAAGCTCGAGAACCTC GAGCCTGAGCACGAGTACAAGTGCGACAGCGAGATCCTGTATAACAATCACAAGTTCACCAACGCCAG CAAGATCATCAAGACCGACTTCGGCTCTCCCGGCGAGCCCCAGATCATCTTCTGTAGATCTGAGGCCG CTCACCAGGGCGTGATCACCTGGAATCCTCCACAGCGGAGCTTCCACAACTTCACCCTGTGCTACATC AAAGAAACCGAGAAGGACTGCCTGAACCTGGACAAGAACCTCATTAAGTACGACCTGCAGAACCTGAA GCCGTACACCAAATACGTGCTGAGCCTGCACGCCTACATCATTGCCAAGGTGCAGAGAAATGGCAGCG CCGCCATGTGCCACTTCACCACAAAAAGCGCCCCTCCAAGCCAAGTGTGGAACATGACCGTGTCTATG ACCAGCGACAACTCCATGCACGTGAAGTGCCGGCCTCCACGGGATAGAAATGGCCCTCACGAGAGATA CCACCTGGAAGTCGAGGCCGGAAATACCCTCGTGCGGAACGAGAGCCACAAGAACTGCGACTTCAGAG TGAAGGACCTGCAGTACAGCACCGACTACACCTTCAAGGCCTACTTCCACAATGGCGACTACCCTGGC GAGCCCTTCATCCTGCACCACAGCACCAGCTACAACAGCAAGTTTATGTACGTGGCCGCTGCTGCCTT CGTGCTGCTGTTCTTTGTTGGCTGCGGAGTGCTGCTGAGCAAGCGGAAGAGAAAGCACATGAAGCTGC TGAGCAGCATCGAGCAGGCCTGTGACATCTGCCGGCTGAAGAAACTGAAGTGCAGCAAAGAAAAGCCC AAGTGCGCCAAGTGCCTGAAGAACAACTGGGAGTGCCGGTACAGCCCCAAGACCAAGAGAAGCCCTCT GACAAGAGCCCACCTGACCGAGGTGGAAAGCCGGCTGGAAAGACTCGAGCAGCTGTTCCTGCTGATCT TCCCCAGAGAAGATCTGGACATGATCCTGAAGATGGACAGCCTGCAGGACATCAAGGCCCTGCTGACC GGACTGTTCGTGCAGGACAACGTGAACAAGGACGCCGTGACCGATAGACTGGCCAGCGTGGAAACCGA CATGCCCCTGACACTGCGGCAGCACAGAATCAGCGCCACAAGCAGCAGCGAGGAAAGCAGCAACAAGG GCCAGAGACAGCTGACAGTGTCTGCTGCTGCTGGCGGAAGCGGAGGATCTGGTGGATCTGATGCCCTG GACGACTTCGACCTGGATATGCTGGGCAGCGACGCCCTGGATGATTTCGATCTCGACATGCTCGGCTC CGACGCTCTCGACGACTTTGATTTGGACATGTTGGGCTCCGATGCACTTGATGATTTTGACTTGGATA TGCTCGGAAGCCGGGCCAAACGATCTGGCTCTGGCCAGTGTACCAACTATGCCCTGCTCAAGCTCGCT GGCGACGTCGAGTCTAACCCTGGACCAATGGGAGCTGGCGCTACAGGCAGAGCTATGGATGGACCTAG ACTGCTGCTGCTCCTGCTTCTGGGAGTGTCTCTTGGCGGAGCCAAAGAGGCCTGTCCTACCGGCCTGT ATACACACTCTGGCGAGTGCTGCAAGGCCTGCAATCTTGGAGAAGGCGTCGCACAGCCTTGCGGCGCT AATCAGACAGTGTGCGAGCCTTGCCTGGACAGCGTGACCTTTAGCGACGTGGTGTCAGCCACCGAGCC ATGCAAGCCATGTACCGAGTGTGTGGGCCTGCAGAGCATGTCTGCCCCTTGCGTGGAAGCTGACGATG CCGTGTGTAGATGCGCCTACGGCTACTACCAGGACGAGACAACAGGCAGATGCGAGGCCTGTAGAGTG TGCGAAGCTGGATCTGGCCTGGTGTTCAGCTGCCAAGACAAGCAGAACACCGTGTGCGAGGAATGCCC CGATGGCACCTATAGCGACGAGGCCAACCATGTGGATCCCTGCCTGCCTTGTACCGTGTGTGAAGATA CCGAGCGGCAGCTGCGCGAGTGTACAAGATGGGCTGATGCCGAGTGCGAAGAGATCCCTGGCAGATGG ATCACCAGAAGCACACCTCCAGAGGGCAGCGATAGCACAGCCCCTTCTACACAAGAGCCCGAGGCTCC TCCTGAGCAGGACCTGATTGCTTCTACAGTGGCTGGCGTCGTGACCACCGTGATGGGATCTAGTCAGC CCGTGGTCACCAGAGGCACCACCGACAATCTGATCCCCGTGTACTGTAGCATCCTGGCCGCCGTGGTT GTTGGACTGGTGGCCTATATCGCCTTCAAGCGGTGGAACAGCTGA(SEQ ID NO:94)Attorney Docket No. 44807-0518WO1 / P18835-01SNIPR-3CD8a SP - myc tag - BB7.2 - CD45 ECD - CD45 TMD - CD45 JMD - Gal4DBD_VP64 TF - E2A -tNGFRAmino Acid Sequence for SNIPR-3 MALPVTALLLPLALLLHAARPEQKLISEEDLQVQLQQSGPELVKPGASVKMSCKASGYTFTSYHIQWV KQRPGQGLEWIGWIYPGDGSTQYNEKFKGKTTLTADKSSSTAYMLLSSLTSEDSAIYFCAREGTYYAM DYWGQGTSVTVSSGGGGSGGGGSGGGGSDIVMTQAPLSLPVSLGDQVSISCRSSQSIVHSNGNTYLEW YLQKPGQSPKLLIYKVSNRFSGVPDRFSGSGSGTDFTLKISRVEAEDLGVYYCFQGSHVPRTFGGGTK LELKRTQSPTPSPTGLTTAKMPSVPLSSDPLPTHTTAFSPASTFERENDFSETTTSLSPDNTSTQVSP DSLDNASAFNTTGVSSVQTPHLPTHADSQTPSAGTDTQTFSGSAANAKLNPTPGSNAISDVPGERSTA STFPTDPVSPLTTTLSLAHHSSAALPARTSNTTITANTSDAYLNASETTTLSPSGSAVISTTTIATTP SKPTCDEKYANITVDYLYNKETKLFTAKLNVNENVECGNNTCTNNEVHNLTECKNASVSISHNSCTAP DKTLILDVPPGVEKFQLHDCTQVEKADTTICLKWKNIETFTCDTQNITYRFQCGNMIFDNKEIKLENL EPEHEYKCDSEILYNNHKFTNASKIIKTDFGSPGEPQIIFCRSEAAHQGVITWNPPQRSFHNFTLCYI KETEKDCLNLDKNLIKYDLQNLKPYTKYVLSLHAYIIAKVQRNGSAAMCHFTTKSAPPSQVWNMTVSM TSDNSMHVKCRPPRDRNGPHERYHLEVEAGNTLVRNESHKNCDFRVKDLQYSTDYTFKAYFHNGDYPG EPFILHHSTSYNSKALIAFLAFLIIVTSIALLVVLYKIYDLHKKRMKLLSSIEQACDICRLKKLKCSK EKPKCAKCLKNNWECRYSPKTKRSPLTRAHLTEVESRLERLEQLFLLIFPREDLDMILKMDSLQDIKA LLTGLFVQDNVNKDAVTDRLASVETDMPLTLRQHRISATSSSEESSNKGQRQLTVSAAAGGSGGSGGS DALDDFDLDMLGSDALDDFDLDMLGSDALDDFDLDMLGSDALDDFDLDMLGSRAKRSGSGQCTNYALL KLAGDVESNPGPMGAGATGRAMDGPRLLLLLLLGVSLGGAKEACPTGLYTHSGECCKACNLGEGVAQP CGANQTVCEPCLDSVTFSDVVSATEPCKPCTECVGLQSMSAPCVEADDAVCRCAYGYYQDETTGRCEA CRVCEAGSGLVFSCQDKQNTVCEECPDGTYSDEANHVDPCLPCTVCEDTERQLRECTRWADAECEEIP GRWITRSTPPEGSDSTAPSTQEPEAPPEQDLIASTVAGVVTTVMGSSQPVVTRGTTDNLIPVYCSILA AVVVGL VAY I AFKRWNS *(SEQ ID NO:95)Nucleic Acid Sequence for SNIPR-3 ATGGCTCTGCCTGTGACAGCTCTGCTGCTGCCTCTGGCTCTGCTTCTGCATGCCGCTAGACCTGAGCA GAAGCTGATCTCCGAAGAGGACCTGCAGGTTCAGCTGCAGCAGTCTGGACCTGAGCTGGTTAAGCCTG GCGCTTCCGTGAAGATGAGCTGCAAGGCCAGCGGCTACACCTTCACCAGCTACCACATCCAGTGGGTC AAGCAGAGGCCTGGACAGGGACTCGAGTGGATCGGCTGGATCTATCCTGGCGACGGCAGCACCCAGTA CAACGAGAAGTTCAAGGGCAAGACCACACTGACCGCCGACAAGAGCAGCAGCACAGCCTACATGCTGC TGAGCAGCCTGACCAGCGAGGACAGCGCCATCTACTTTTGTGCCAGAGAGGGCACCTACTACGCCATG GATTATTGGGGCCAGGGCACCAGCGTGACAGTCTCTTCTGGTGGCGGAGGATCTGGCGGAGGTGGAAG CGGCGGAGGCGGATCTGATATCGTGATGACACAGGCCCCTCTGAGCCTGCCTGTGTCTCTGGGAGATC AGGTGTCCATCAGCTGTCGGAGCAGCCAGAGCATCGTGCACAGCAACGGCAACACCTACCTGGAATGG TATCTGCAGAAGCCCGGACAGAGCCCCAAGCTGCTGATCTACAAGGTGTCCAACCGGTTCAGCGGCGT GCCCGATAGATTTTCTGGCTCTGGCAGCGGCACCGACTTCACCCTGAAGATCTCTAGAGTGGAAGCCG AGGACCTGGGCGTGTACTACTGCTTCCAAGGCAGCCACGTGCCAAGAACCTTTGGCGGCGGAACAAAG CTGGAACTGAAGCGGACACAGAGCCCCACACCATCTCCAACAGGACTGACCACCGCCAAGATGCCTAG CGTGCCCCTCTCTTCTGACCCTCTGCCTACACACACCACCGCTTTTAGCCCTGCCAGCACCTTCGAGA GAGAGAACGACTTCAGCGAGACAACCACCTCTCTGAGCCCCGACAACACCAGCACACAGGTGTCCCCA GACAGCCTGGATAATGCCAGCGCCTTCAATACCACCGGCGTGTCCTCTGTGCAGACCCCTCATCTGCC AACACACGCCGATAGCCAGACACCTTCTGCCGGCACCGATACACAGACCTTTTCTGGCTCTGCCGCCAAttorney Docket No. 44807-0518WO1 / P18835-01ACGCCAAGCTGAACCCTACACCTGGCAGCAACGCCATCTCTGATGTGCCTGGCGAGAGAAGCACCGCC AGCACATTTCCAACAGACCCCGTGTCTCCCCTGACCACCACACTGTCTCTGGCCCACCATAGCTCTGC TGCCCTGCCTGCCAGAACCAGCAACACCACCATCACCGCCAATACCAGCGACGCCTACCTGAACGCCA GCGAAACCACAACACTGAGCCCTAGCGGAAGCGCCGTGATCAGCACAACCACAATCGCCACCACACCT AGCAAGCCTACCTGCGACGAGAAGTACGCCAACATCACCGTGGACTACCTGTACAACAAAGAGACAAA GCTGTTCACGGCCAAGCTCAACGTGAACGAGAACGTGGAATGCGGCAACAATACCTGCACCAACAACG AGGTGCACAACCTGACCGAGTGCAAGAACGCCTCCGTGTCCATCAGCCACAACAGCTGCACAGCCCCT GACAAGACCCTGATCCTGGATGTGCCTCCTGGCGTGGAAAAGTTCCAGCTGCACGATTGCACCCAGGT GGAAAAGGCCGATACCACCATCTGCCTGAAGTGGAAGAACATCGAGACATTCACCTGTGACACCCAGA ACATCACCTACCGGTTCCAGTGCGGCAATATGATCTTCGATAACAAAGAAATCAAGCTCGAGAACCTC GAGCCTGAGCACGAGTACAAGTGCGACAGCGAGATCCTGTATAACAATCACAAGTTCACCAACGCCAG CAAGATCATCAAGACCGACTTCGGCTCTCCCGGCGAGCCCCAGATCATCTTCTGTAGATCTGAGGCCG CTCACCAGGGCGTGATCACCTGGAATCCTCCACAGCGGAGCTTCCACAACTTCACCCTGTGCTACATC AAAGAAACCGAGAAGGACTGCCTGAACCTGGACAAGAACCTCATTAAGTACGACCTGCAGAACCTGAA GCCGTACACCAAATACGTGCTGAGCCTGCACGCCTACATCATTGCCAAGGTGCAGAGAAATGGCAGCG CCGCCATGTGCCACTTCACCACAAAAAGCGCCCCTCCAAGCCAAGTGTGGAACATGACCGTGTCTATG ACCAGCGACAACTCCATGCACGTGAAGTGCCGGCCTCCACGGGATAGAAATGGCCCTCACGAGAGATA CCACCTGGAAGTCGAGGCCGGAAATACCCTCGTGCGGAACGAGAGCCACAAGAACTGCGACTTCAGAG TGAAGGACCTGCAGTACAGCACCGACTACACCTTCAAGGCCTACTTCCACAATGGCGACTACCCTGGC GAGCCCTTCATCCTGCACCACAGCACCAGCTACAACAGCAAGGCACTTATCGCGTTCCTCGCGTTTCT CATTATTGTTACATCCATAGCTTTGCTTGTTGTACTTTACAAGATTTATGACCTTCATAAGAAACGAA TGAAGCTGCTGAGCAGCATCGAGCAGGCCTGTGACATCTGCCGGCTGAAGAAACTGAAGTGCAGCAAA GAAAAGCCCAAGTGCGCCAAGTGCCTGAAGAACAACTGGGAGTGCCGGTACAGCCCCAAGACCAAGAG AAGCCCTCTGACAAGAGCCCACCTGACCGAGGTGGAAAGCCGGCTGGAAAGACTCGAGCAGCTGTTCC TGCTGATCTTCCCCAGAGAAGATCTGGACATGATCCTGAAGATGGACAGCCTGCAGGACATCAAGGCC CTGCTGACCGGACTGTTCGTGCAGGACAACGTGAACAAGGACGCCGTGACCGATAGACTGGCCAGCGT GGAAACCGACATGCCCCTGACACTGCGGCAGCACAGAATCAGCGCCACAAGCAGCAGCGAGGAAAGCA GCAACAAGGGCCAGAGACAGCTGACAGTGTCTGCTGCTGCTGGCGGAAGCGGAGGATCTGGTGGATCT GATGCCCTGGACGACTTCGACCTGGATATGCTGGGCAGCGACGCCCTGGATGATTTCGATCTCGACAT GCTCGGCTCCGACGCTCTCGACGACTTTGATTTGGACATGTTGGGCTCCGATGCACTTGATGATTTTG ACTTGGATATGCTCGGAAGCCGGGCCAAACGATCTGGCTCTGGCCAGTGTACCAACTATGCCCTGCTC AAGCTCGCTGGCGACGTCGAGTCTAACCCTGGACCAATGGGAGCTGGCGCTACAGGCAGAGCTATGGA TGGACCTAGACTGCTGCTGCTCCTGCTTCTGGGAGTGTCTCTTGGCGGAGCCAAAGAGGCCTGTCCTA CCGGCCTGTATACACACTCTGGCGAGTGCTGCAAGGCCTGCAATCTTGGAGAAGGCGTCGCACAGCCT TGCGGCGCTAATCAGACAGTGTGCGAGCCTTGCCTGGACAGCGTGACCTTTAGCGACGTGGTGTCAGC CACCGAGCCATGCAAGCCATGTACCGAGTGTGTGGGCCTGCAGAGCATGTCTGCCCCTTGCGTGGAAG CTGACGATGCCGTGTGTAGATGCGCCTACGGCTACTACCAGGACGAGACAACAGGCAGATGCGAGGCC TGTAGAGTGTGCGAAGCTGGATCTGGCCTGGTGTTCAGCTGCCAAGACAAGCAGAACACCGTGTGCGA GGAATGCCCCGATGGCACCTATAGCGACGAGGCCAACCATGTGGATCCCTGCCTGCCTTGTACCGTGT GTGAAGATACCGAGCGGCAGCTGCGCGAGTGTACAAGATGGGCTGATGCCGAGTGCGAAGAGATCCCT GGCAGATGGATCACCAGAAGCACACCTCCAGAGGGCAGCGATAGCACAGCCCCTTCTACACAAGAGCC CGAGGCTCCTCCTGAGCAGGACCTGATTGCTTCTACAGTGGCTGGCGTCGTGACCACCGTGATGGGAT CTAGTCAGCCCGTGGTCACCAGAGGCACCACCGACAATCTGATCCCCGTGTACTGTAGCATCCTGGCC GCCGTGGTTGTTGGACTGGTGGCCTATATCGCCTTCAAGCGGTGGAACAGCTGA(SEQ ID NO:96)Attorney Docket No. 44807-0518WO1 / P18835-01SNIPR-2 G318A DesignCD8a SP - myc tag - BB7.2 - CD45 ECD - NOTCH1 TMD G318A - NOTCH2 JMD -Gal4DBD_VP64 TF - E2A - tNGFRAmino Acid Sequence for SNIPR-2 G318A MALPVTALLLPLALLLHAARPEQKLISEEDLQVQLQQSGPELVKPGASVKMSCKASGYTFTSYHIQWV KQRPGQGLEWIGWIYPGDGSTQYNEKFKGKTTLTADKSSSTAYMLLSSLTSEDSAIYFCAREGTYYAM DYWGQGTSVTVSSGGGGSGGGGSGGGGSDIVMTQAPLSLPVSLGDQVSISCRSSQSIVHSNGNTYLEW YLQKPGQSPKLLIYKVSNRFSGVPDRFSGSGSGTDFTLKISRVEAEDLGVYYCFQGSHVPRTFGGGTK LELKRTQSPTPSPTGLTTAKMPSVPLSSDPLPTHTTAFSPASTFERENDFSETTTSLSPDNTSTQVSP DSLDNASAFNTTGVSSVQTPHLPTHADSQTPSAGTDTQTFSGSAANAKLNPTPGSNAISDVPGERSTA STFPTDPVSPLTTTLSLAHHSSAALPARTSNTTITANTSDAYLNASETTTLSPSGSAVISTTTIATTP SKPTCDEKYANITVDYLYNKETKLFTAKLNVNENVECGNNTCTNNEVHNLTECKNASVSISHNSCTAP DKTLILDVPPGVEKFQLHDCTQVEKADTTICLKWKNIETFTCDTQNITYRFQCGNMIFDNKEIKLENL EPEHEYKCDSEILYNNHKFTNASKIIKTDFGSPGEPQIIFCRSEAAHQGVITWNPPQRSFHNFTLCYI KETEKDCLNLDKNLIKYDLQNLKPYTKYVLSLHAYIIAKVQRNGSAAMCHFTTKSAPPSQVWNMTVSM TSDNSMHVKCRPPRDRNGPHERYHLEVEAGNTLVRNESHKNCDFRVKDLQYSTDYTFKAYFHNGDYPG EPFILHHSTSYNSKFMYVAAAAFVLLFFVGCAVLLSKRKRKHMKLLSSIEQACDICRLKKLKCSKEKP KCAKCLKNNWECRYSPKTKRSPLTRAHLTEVESRLERLEQLFLLIFPREDLDMILKMDSLQDIKALLT GLFVQDNVNKDAVTDRLASVETDMPLTLRQHRISATSSSEESSNKGQRQLTVSAAAGGSGGSGGSDAL DDFDLDMLGSDALDDFDLDMLGSDALDDFDLDMLGSDALDDFDLDMLGSRAKRSGSGQCTNYALLKLA GDVESNPGPMGAGATGRAMDGPRLLLLLLLGVSLGGAKEACPTGLYTHSGECCKACNLGEGVAQPCGA NQTVCEPCLDSVTFSDVVSATEPCKPCTECVGLQSMSAPCVEADDAVCRCAYGYYQDETTGRCEACRV CEAGSGLVFSCQDKQNTVCEECPDGTYSDEANHVDPCLPCTVCEDTERQLRECTRWADAECEEIPGRW ITRSTPPEGSDSTAPSTQEPEAPPEQDLIASTVAGVVTTVMGSSQPVVTRGTTDNLIPVYCSILAAVV VGLVAY IAFKRWNS *(SEQ ID NO:97)Nucleic Acid Sequence for SNIPR-2 G318A ATGGCTCTGCCTGTGACAGCTCTGCTGCTGCCTCTGGCTCTGCTTCTGCATGCCGCTAGACCTGAGCA GAAGCTGATCTCCGAAGAGGACCTGCAGGTTCAGCTGCAGCAGTCTGGACCTGAGCTGGTTAAGCCTG GCGCTTCCGTGAAGATGAGCTGCAAGGCCAGCGGCTACACCTTCACCAGCTACCACATCCAGTGGGTC AAGCAGAGGCCTGGACAGGGACTCGAGTGGATCGGCTGGATCTATCCTGGCGACGGCAGCACCCAGTA CAACGAGAAGTTCAAGGGCAAGACCACACTGACCGCCGACAAGAGCAGCAGCACAGCCTACATGCTGC TGAGCAGCCTGACCAGCGAGGACAGCGCCATCTACTTTTGTGCCAGAGAGGGCACCTACTACGCCATG GATTATTGGGGCCAGGGCACCAGCGTGACAGTCTCTTCTGGTGGCGGAGGATCTGGCGGAGGTGGAAG CGGCGGAGGCGGATCTGATATCGTGATGACACAGGCCCCTCTGAGCCTGCCTGTGTCTCTGGGAGATC AGGTGTCCATCAGCTGTCGGAGCAGCCAGAGCATCGTGCACAGCAACGGCAACACCTACCTGGAATGG TATCTGCAGAAGCCCGGACAGAGCCCCAAGCTGCTGATCTACAAGGTGTCCAACCGGTTCAGCGGCGT GCCCGATAGATTTTCTGGCTCTGGCAGCGGCACCGACTTCACCCTGAAGATCTCTAGAGTGGAAGCCG AGGACCTGGGCGTGTACTACTGCTTCCAAGGCAGCCACGTGCCAAGAACCTTTGGCGGCGGAACAAAG CTGGAACTGAAGCGGACACAGAGCCCCACACCATCTCCAACAGGACTGACCACCGCCAAGATGCCTAG CGTGCCCCTCTCTTCTGACCCTCTGCCTACACACACCACCGCTTTTAGCCCTGCCAGCACCTTCGAGA GAGAGAACGACTTCAGCGAGACAACCACCTCTCTGAGCCCCGACAACACCAGCACACAGGTGTCCCCA GACAGCCTGGATAATGCCAGCGCCTTCAATACCACCGGCGTGTCCTCTGTGCAGACCCCTCATCTGCC AACACACGCCGATAGCCAGACACCTTCTGCCGGCACCGATACACAGACCTTTTCTGGCTCTGCCGCCAAttorney Docket No. 44807-0518WO1 / P18835-01ACGCCAAGCTGAACCCTACACCTGGCAGCAACGCCATCTCTGATGTGCCTGGCGAGAGAAGCACCGCC AGCACATTTCCAACAGACCCCGTGTCTCCCCTGACCACCACACTGTCTCTGGCCCACCATAGCTCTGC TGCCCTGCCTGCCAGAACCAGCAACACCACCATCACCGCCAATACCAGCGACGCCTACCTGAACGCCA GCGAAACCACAACACTGAGCCCTAGCGGAAGCGCCGTGATCAGCACAACCACAATCGCCACCACACCT AGCAAGCCTACCTGCGACGAGAAGTACGCCAACATCACCGTGGACTACCTGTACAACAAAGAGACAAA GCTGTTCACGGCCAAGCTCAACGTGAACGAGAACGTGGAATGCGGCAACAATACCTGCACCAACAACG AGGTGCACAACCTGACCGAGTGCAAGAACGCCTCCGTGTCCATCAGCCACAACAGCTGCACAGCCCCT GACAAGACCCTGATCCTGGATGTGCCTCCTGGCGTGGAAAAGTTCCAGCTGCACGATTGCACCCAGGT GGAAAAGGCCGATACCACCATCTGCCTGAAGTGGAAGAACATCGAGACATTCACCTGTGACACCCAGA ACATCACCTACCGGTTCCAGTGCGGCAATATGATCTTCGATAACAAAGAAATCAAGCTCGAGAACCTC GAGCCTGAGCACGAGTACAAGTGCGACAGCGAGATCCTGTATAACAATCACAAGTTCACCAACGCCAG CAAGATCATCAAGACCGACTTCGGCTCTCCCGGCGAGCCCCAGATCATCTTCTGTAGATCTGAGGCCG CTCACCAGGGCGTGATCACCTGGAATCCTCCACAGCGGAGCTTCCACAACTTCACCCTGTGCTACATC AAAGAAACCGAGAAGGACTGCCTGAACCTGGACAAGAACCTCATTAAGTACGACCTGCAGAACCTGAA GCCGTACACCAAATACGTGCTGAGCCTGCACGCCTACATCATTGCCAAGGTGCAGAGAAATGGCAGCG CCGCCATGTGCCACTTCACCACAAAAAGCGCCCCTCCAAGCCAAGTGTGGAACATGACCGTGTCTATG ACCAGCGACAACTCCATGCACGTGAAGTGCCGGCCTCCACGGGATAGAAATGGCCCTCACGAGAGATA CCACCTGGAAGTCGAGGCCGGAAATACCCTCGTGCGGAACGAGAGCCACAAGAACTGCGACTTCAGAG TGAAGGACCTGCAGTACAGCACCGACTACACCTTCAAGGCCTACTTCCACAATGGCGACTACCCTGGC GAGCCCTTCATCCTGCACCACAGCACCAGCTACAACAGCAAGTTTATGTACGTGGCCGCTGCTGCCTT CGTGCTGCTGTTCTTTGTTGGCTGCGCCGTGCTGCTGAGCAAGCGGAAGAGAAAGCACATGAAGCTGC TGAGCAGCATCGAGCAGGCCTGTGACATCTGCCGGCTGAAGAAACTGAAGTGCAGCAAAGAAAAGCCC AAGTGCGCCAAGTGCCTGAAGAACAACTGGGAGTGCCGGTACAGCCCCAAGACCAAGAGAAGCCCTCT GACAAGAGCCCACCTGACCGAGGTGGAAAGCCGGCTGGAAAGACTCGAGCAGCTGTTCCTGCTGATCT TCCCCAGAGAAGATCTGGACATGATCCTGAAGATGGACAGCCTGCAGGACATCAAGGCCCTGCTGACC GGACTGTTCGTGCAGGACAACGTGAACAAGGACGCCGTGACCGATAGACTGGCCAGCGTGGAAACCGA CATGCCCCTGACACTGCGGCAGCACAGAATCAGCGCCACAAGCAGCAGCGAGGAAAGCAGCAACAAGG GCCAGAGACAGCTGACAGTGTCTGCTGCTGCTGGCGGAAGCGGAGGATCTGGTGGATCTGATGCCCTG GACGACTTCGACCTGGATATGCTGGGCAGCGACGCCCTGGATGATTTCGATCTCGACATGCTCGGCTC CGACGCTCTCGACGACTTTGATTTGGACATGTTGGGCTCCGATGCACTTGATGATTTTGACTTGGATA TGCTCGGAAGCCGGGCCAAACGATCTGGCTCTGGCCAGTGTACCAACTATGCCCTGCTCAAGCTCGCT GGCGACGTCGAGTCTAACCCTGGACCAATGGGAGCTGGCGCTACAGGCAGAGCTATGGATGGACCTAG ACTGCTGCTGCTCCTGCTTCTGGGAGTGTCTCTTGGCGGAGCCAAAGAGGCCTGTCCTACCGGCCTGT ATACACACTCTGGCGAGTGCTGCAAGGCCTGCAATCTTGGAGAAGGCGTCGCACAGCCTTGCGGCGCT AATCAGACAGTGTGCGAGCCTTGCCTGGACAGCGTGACCTTTAGCGACGTGGTGTCAGCCACCGAGCC ATGCAAGCCATGTACCGAGTGTGTGGGCCTGCAGAGCATGTCTGCCCCTTGCGTGGAAGCTGACGATG CCGTGTGTAGATGCGCCTACGGCTACTACCAGGACGAGACAACAGGCAGATGCGAGGCCTGTAGAGTG TGCGAAGCTGGATCTGGCCTGGTGTTCAGCTGCCAAGACAAGCAGAACACCGTGTGCGAGGAATGCCC CGATGGCACCTATAGCGACGAGGCCAACCATGTGGATCCCTGCCTGCCTTGTACCGTGTGTGAAGATA CCGAGCGGCAGCTGCGCGAGTGTACAAGATGGGCTGATGCCGAGTGCGAAGAGATCCCTGGCAGATGG ATCACCAGAAGCACACCTCCAGAGGGCAGCGATAGCACAGCCCCTTCTACACAAGAGCCCGAGGCTCC TCCTGAGCAGGACCTGATTGCTTCTACAGTGGCTGGCGTCGTGACCACCGTGATGGGATCTAGTCAGC CCGTGGTCACCAGAGGCACCACCGACAATCTGATCCCCGTGTACTGTAGCATCCTGGCCGCCGTGGTT GTTGGACTGGTGGCCTATATCGCCTTCAAGCGGTGGAACAGCTGA(SEQ ID NO:98)Attorney Docket No. 44807-0518WO1 / P18835-01SNIPR-2 V319A DesignCD8a SP - myc tag - BB7.2 - CD45 ECD - NOTCH1 TMD V319A - NOTCH2 JMD -Gal4DBD_VP64 TF - E2A - tNGFRAmino Acid Sequence for SNIPR-2 V319A MALPVTALLLPLALLLHAARPEQKLISEEDLQVQLQQSGPELVKPGASVKMSCKASGYTFTSYHIQWV KQRPGQGLEWIGWIYPGDGSTQYNEKFKGKTTLTADKSSSTAYMLLSSLTSEDSAIYFCAREGTYYAM DYWGQGTSVTVSSGGGGSGGGGSGGGGSDIVMTQAPLSLPVSLGDQVSISCRSSQSIVHSNGNTYLEW YLQKPGQSPKLLIYKVSNRFSGVPDRFSGSGSGTDFTLKISRVEAEDLGVYYCFQGSHVPRTFGGGTK LELKRTQSPTPSPTGLTTAKMPSVPLSSDPLPTHTTAFSPASTFERENDFSETTTSLSPDNTSTQVSP DSLDNASAFNTTGVSSVQTPHLPTHADSQTPSAGTDTQTFSGSAANAKLNPTPGSNAISDVPGERSTA STFPTDPVSPLTTTLSLAHHSSAALPARTSNTTITANTSDAYLNASETTTLSPSGSAVISTTTIATTP SKPTCDEKYANITVDYLYNKETKLFTAKLNVNENVECGNNTCTNNEVHNLTECKNASVSISHNSCTAP DKTLILDVPPGVEKFQLHDCTQVEKADTTICLKWKNIETFTCDTQNITYRFQCGNMIFDNKEIKLENL EPEHEYKCDSEILYNNHKFTNASKIIKTDFGSPGEPQIIFCRSEAAHQGVITWNPPQRSFHNFTLCYI KETEKDCLNLDKNLIKYDLQNLKPYTKYVLSLHAYIIAKVQRNGSAAMCHFTTKSAPPSQVWNMTVSM TSDNSMHVKCRPPRDRNGPHERYHLEVEAGNTLVRNESHKNCDFRVKDLQYSTDYTFKAYFHNGDYPG EPFILHHSTSYNSKFMYVAAAAFVLLFFVGCGALLSKRKRKHMKLLSSIEQACDICRLKKLKCSKEKP KCAKCLKNNWECRYSPKTKRSPLTRAHLTEVESRLERLEQLFLLIFPREDLDMILKMDSLQDIKALLT GLFVQDNVNKDAVTDRLASVETDMPLTLRQHRISATSSSEESSNKGQRQLTVSAAAGGSGGSGGSDAL DDFDLDMLGSDALDDFDLDMLGSDALDDFDLDMLGSDALDDFDLDMLGSRAKRSGSGQCTNYALLKLA GDVESNPGPMGAGATGRAMDGPRLLLLLLLGVSLGGAKEACPTGLYTHSGECCKACNLGEGVAQPCGA NQTVCEPCLDSVTFSDVVSATEPCKPCTECVGLQSMSAPCVEADDAVCRCAYGYYQDETTGRCEACRV CEAGSGLVFSCQDKQNTVCEECPDGTYSDEANHVDPCLPCTVCEDTERQLRECTRWADAECEEIPGRW ITRSTPPEGSDSTAPSTQEPEAPPEQDLIASTVAGVVTTVMGSSQPVVTRGTTDNLIPVYCSILAAVV VGLVAY IAFKRWNS *(SEQ ID NO:99)Nucleic Acid Sequence for SNIPR-2 V319 A ATGGCTCTGCCTGTGACAGCTCTGCTGCTGCCTCTGGCTCTGCTTCTGCATGCCGCTAGACCTGAGCA GAAGCTGATCTCCGAAGAGGACCTGCAGGTTCAGCTGCAGCAGTCTGGACCTGAGCTGGTTAAGCCTG GCGCTTCCGTGAAGATGAGCTGCAAGGCCAGCGGCTACACCTTCACCAGCTACCACATCCAGTGGGTC AAGCAGAGGCCTGGACAGGGACTCGAGTGGATCGGCTGGATCTATCCTGGCGACGGCAGCACCCAGTA CAACGAGAAGTTCAAGGGCAAGACCACACTGACCGCCGACAAGAGCAGCAGCACAGCCTACATGCTGC TGAGCAGCCTGACCAGCGAGGACAGCGCCATCTACTTTTGTGCCAGAGAGGGCACCTACTACGCCATG GATTATTGGGGCCAGGGCACCAGCGTGACAGTCTCTTCTGGTGGCGGAGGATCTGGCGGAGGTGGAAG CGGCGGAGGCGGATCTGATATCGTGATGACACAGGCCCCTCTGAGCCTGCCTGTGTCTCTGGGAGATC AGGTGTCCATCAGCTGTCGGAGCAGCCAGAGCATCGTGCACAGCAACGGCAACACCTACCTGGAATGG TATCTGCAGAAGCCCGGACAGAGCCCCAAGCTGCTGATCTACAAGGTGTCCAACCGGTTCAGCGGCGT GCCCGATAGATTTTCTGGCTCTGGCAGCGGCACCGACTTCACCCTGAAGATCTCTAGAGTGGAAGCCG AGGACCTGGGCGTGTACTACTGCTTCCAAGGCAGCCACGTGCCAAGAACCTTTGGCGGCGGAACAAAG CTGGAACTGAAGCGGACACAGAGCCCCACACCATCTCCAACAGGACTGACCACCGCCAAGATGCCTAG CGTGCCCCTCTCTTCTGACCCTCTGCCTACACACACCACCGCTTTTAGCCCTGCCAGCACCTTCGAGA GAGAGAACGACTTCAGCGAGACAACCACCTCTCTGAGCCCCGACAACACCAGCACACAGGTGTCCCCA GACAGCCTGGATAATGCCAGCGCCTTCAATACCACCGGCGTGTCCTCTGTGCAGACCCCTCATCTGCC AACACACGCCGATAGCCAGACACCTTCTGCCGGCACCGATACACAGACCTTTTCTGGCTCTGCCGCCAAttorney Docket No. 44807-0518WO1 / P18835-01ACGCCAAGCTGAACCCTACACCTGGCAGCAACGCCATCTCTGATGTGCCTGGCGAGAGAAGCACCGCC AGCACATTTCCAACAGACCCCGTGTCTCCCCTGACCACCACACTGTCTCTGGCCCACCATAGCTCTGC TGCCCTGCCTGCCAGAACCAGCAACACCACCATCACCGCCAATACCAGCGACGCCTACCTGAACGCCA GCGAAACCACAACACTGAGCCCTAGCGGAAGCGCCGTGATCAGCACAACCACAATCGCCACCACACCT AGCAAGCCTACCTGCGACGAGAAGTACGCCAACATCACCGTGGACTACCTGTACAACAAAGAGACAAA GCTGTTCACGGCCAAGCTCAACGTGAACGAGAACGTGGAATGCGGCAACAATACCTGCACCAACAACG AGGTGCACAACCTGACCGAGTGCAAGAACGCCTCCGTGTCCATCAGCCACAACAGCTGCACAGCCCCT GACAAGACCCTGATCCTGGATGTGCCTCCTGGCGTGGAAAAGTTCCAGCTGCACGATTGCACCCAGGT GGAAAAGGCCGATACCACCATCTGCCTGAAGTGGAAGAACATCGAGACATTCACCTGTGACACCCAGA ACATCACCTACCGGTTCCAGTGCGGCAATATGATCTTCGATAACAAAGAAATCAAGCTCGAGAACCTC GAGCCTGAGCACGAGTACAAGTGCGACAGCGAGATCCTGTATAACAATCACAAGTTCACCAACGCCAG CAAGATCATCAAGACCGACTTCGGCTCTCCCGGCGAGCCCCAGATCATCTTCTGTAGATCTGAGGCCG CTCACCAGGGCGTGATCACCTGGAATCCTCCACAGCGGAGCTTCCACAACTTCACCCTGTGCTACATC AAAGAAACCGAGAAGGACTGCCTGAACCTGGACAAGAACCTCATTAAGTACGACCTGCAGAACCTGAA GCCGTACACCAAATACGTGCTGAGCCTGCACGCCTACATCATTGCCAAGGTGCAGAGAAATGGCAGCG CCGCCATGTGCCACTTCACCACAAAAAGCGCCCCTCCAAGCCAAGTGTGGAACATGACCGTGTCTATG ACCAGCGACAACTCCATGCACGTGAAGTGCCGGCCTCCACGGGATAGAAATGGCCCTCACGAGAGATA CCACCTGGAAGTCGAGGCCGGAAATACCCTCGTGCGGAACGAGAGCCACAAGAACTGCGACTTCAGAG TGAAGGACCTGCAGTACAGCACCGACTACACCTTCAAGGCCTACTTCCACAATGGCGACTACCCTGGC GAGCCCTTCATCCTGCACCACAGCACCAGCTACAACAGCAAGTTTATGTACGTGGCCGCTGCTGCCTT CGTGCTGCTGTTCTTTGTTGGCTGCGGAGCTCTGCTGAGCAAGCGGAAGAGAAAGCACATGAAGCTGC TGAGCAGCATCGAGCAGGCCTGTGACATCTGCCGGCTGAAGAAACTGAAGTGCAGCAAAGAAAAGCCC AAGTGCGCCAAGTGCCTGAAGAACAACTGGGAGTGCCGGTACAGCCCCAAGACCAAGAGAAGCCCTCT GACAAGAGCCCACCTGACCGAGGTGGAAAGCCGGCTGGAAAGACTCGAGCAGCTGTTCCTGCTGATCT TCCCCAGAGAAGATCTGGACATGATCCTGAAGATGGACAGCCTGCAGGACATCAAGGCCCTGCTGACC GGACTGTTCGTGCAGGACAACGTGAACAAGGACGCCGTGACCGATAGACTGGCCAGCGTGGAAACCGA CATGCCCCTGACACTGCGGCAGCACAGAATCAGCGCCACAAGCAGCAGCGAGGAAAGCAGCAACAAGG GCCAGAGACAGCTGACAGTGTCTGCTGCTGCTGGCGGAAGCGGAGGATCTGGTGGATCTGATGCCCTG GACGACTTCGACCTGGATATGCTGGGCAGCGACGCCCTGGATGATTTCGATCTCGACATGCTCGGCTC CGACGCTCTCGACGACTTTGATTTGGACATGTTGGGCTCCGATGCACTTGATGATTTTGACTTGGATA TGCTCGGAAGCCGGGCCAAACGATCTGGCTCTGGCCAGTGTACCAACTATGCCCTGCTCAAGCTCGCT GGCGACGTCGAGTCTAACCCTGGACCAATGGGAGCTGGCGCTACAGGCAGAGCTATGGATGGACCTAG ACTGCTGCTGCTCCTGCTTCTGGGAGTGTCTCTTGGCGGAGCCAAAGAGGCCTGTCCTACCGGCCTGT ATACACACTCTGGCGAGTGCTGCAAGGCCTGCAATCTTGGAGAAGGCGTCGCACAGCCTTGCGGCGCT AATCAGACAGTGTGCGAGCCTTGCCTGGACAGCGTGACCTTTAGCGACGTGGTGTCAGCCACCGAGCC ATGCAAGCCATGTACCGAGTGTGTGGGCCTGCAGAGCATGTCTGCCCCTTGCGTGGAAGCTGACGATG CCGTGTGTAGATGCGCCTACGGCTACTACCAGGACGAGACAACAGGCAGATGCGAGGCCTGTAGAGTG TGCGAAGCTGGATCTGGCCTGGTGTTCAGCTGCCAAGACAAGCAGAACACCGTGTGCGAGGAATGCCC CGATGGCACCTATAGCGACGAGGCCAACCATGTGGATCCCTGCCTGCCTTGTACCGTGTGTGAAGATA CCGAGCGGCAGCTGCGCGAGTGTACAAGATGGGCTGATGCCGAGTGCGAAGAGATCCCTGGCAGATGG ATCACCAGAAGCACACCTCCAGAGGGCAGCGATAGCACAGCCCCTTCTACACAAGAGCCCGAGGCTCC TCCTGAGCAGGACCTGATTGCTTCTACAGTGGCTGGCGTCGTGACCACCGTGATGGGATCTAGTCAGC CCGTGGTCACCAGAGGCACCACCGACAATCTGATCCCCGTGTACTGTAGCATCCTGGCCGCCGTGGTT GTTGGACTGGTGGCCTATATCGCCTTCAAGCGGTGGAACAGCTGA(SEQ ID NO: 100)Attorney Docket No. 44807-0518WO1 / P18835-01SNIPR-3 Nl-JMD DesignCD8a SP - myc tag - BB7.2 - CD45 ECD - CD45 TMD - NOTCH1 JMD - Gal4DBD_VP64 TF -E2A - tNGFRAmino Acid Sequence for SNIPR-3 Nl-JMD MALPVTALLLPLALLLHAARPEQKLISEEDLQVQLQQSGPELVKPGASVKMSCKASGYTFTSYHIQWV KQRPGQGLEWIGWIYPGDGSTQYNEKFKGKTTLTADKSSSTAYMLLSSLTSEDSAIYFCAREGTYYAM DYWGQGTSVTVSSGGGGSGGGGSGGGGSDIVMTQAPLSLPVSLGDQVSISCRSSQSIVHSNGNTYLEW YLQKPGQSPKLLIYKVSNRFSGVPDRFSGSGSGTDFTLKISRVEAEDLGVYYCFQGSHVPRTFGGGTK LELKRTQSPTPSPTGLTTAKMPSVPLSSDPLPTHTTAFSPASTFERENDFSETTTSLSPDNTSTQVSP DSLDNASAFNTTGVSSVQTPHLPTHADSQTPSAGTDTQTFSGSAANAKLNPTPGSNAISDVPGERSTA STFPTDPVSPLTTTLSLAHHSSAALPARTSNTTITANTSDAYLNASETTTLSPSGSAVISTTTIATTP SKPTCDEKYANITVDYLYNKETKLFTAKLNVNENVECGNNTCTNNEVHNLTECKNASVSISHNSCTAP DKTLILDVPPGVEKFQLHDCTQVEKADTTICLKWKNIETFTCDTQNITYRFQCGNMIFDNKEIKLENL EPEHEYKCDSEILYNNHKFTNASKIIKTDFGSPGEPQIIFCRSEAAHQGVITWNPPQRSFHNFTLCYI KETEKDCLNLDKNLIKYDLQNLKPYTKYVLSLHAYIIAKVQRNGSAAMCHFTTKSAPPSQVWNMTVSM TSDNSMHVKCRPPRDRNGPHERYHLEVEAGNTLVRNESHKNCDFRVKDLQYSTDYTFKAYFHNGDYPG EPFILHHSTSYNSKALIAFLAFLIIVTSIALLVVLRKRRRMKLLSSIEQACDICRLKKLKCSKEKPKC AKCLKNNWECRYSPKTKRSPLTRAHLTEVESRLERLEQLFLLIFPREDLDMILKMDSLQDIKALLTGL FVQDNVNKDAVTDRLASVETDMPLTLRQHRISATSSSEESSNKGQRQLTVSAAAGGSGGSGGSDALDD FDLDMLGSDALDDFDLDMLGSDALDDFDLDMLGSDALDDFDLDMLGSRAKRSGSGQCTNYALLKLAGD VESNPGPMGAGATGRAMDGPRLLLLLLLGVSLGGAKEACPTGLYTHSGECCKACNLGEGVAQPCGANQ TVCEPCLDSVTFSDVVSATEPCKPCTECVGLQSMSAPCVEADDAVCRCAYGYYQDETTGRCEACRVCE AGSGLVFSCQDKQNTVCEECPDGTYSDEANHVDPCLPCTVCEDTERQLRECTRWADAECEEIPGRWIT RSTPPEGSDSTAPSTQEPEAPPEQDLIASTVAGVVTTVMGSSQPVVTRGTTDNLIPVYCSILAAVVVG LVAYI FKRWNS*(SEQ ID NO: 101)Nucleic Acid Sequence for SNIPR-3 Nl-JMD ATGGCTCTGCCTGTGACAGCTCTGCTGCTGCCTCTGGCTCTGCTTCTGCATGCCGCTAGACCTGAGCA GAAGCTGATCTCCGAAGAGGACCTGCAGGTTCAGCTGCAGCAGTCTGGACCTGAGCTGGTTAAGCCTG GCGCTTCCGTGAAGATGAGCTGCAAGGCCAGCGGCTACACCTTCACCAGCTACCACATCCAGTGGGTC AAGCAGAGGCCTGGACAGGGACTCGAGTGGATCGGCTGGATCTATCCTGGCGACGGCAGCACCCAGTA CAACGAGAAGTTCAAGGGCAAGACCACACTGACCGCCGACAAGAGCAGCAGCACAGCCTACATGCTGC TGAGCAGCCTGACCAGCGAGGACAGCGCCATCTACTTTTGTGCCAGAGAGGGCACCTACTACGCCATG GATTATTGGGGCCAGGGCACCAGCGTGACAGTCTCTTCTGGTGGCGGAGGATCTGGCGGAGGTGGAAG CGGCGGAGGCGGATCTGATATCGTGATGACACAGGCCCCTCTGAGCCTGCCTGTGTCTCTGGGAGATC AGGTGTCCATCAGCTGTCGGAGCAGCCAGAGCATCGTGCACAGCAACGGCAACACCTACCTGGAATGG TATCTGCAGAAGCCCGGACAGAGCCCCAAGCTGCTGATCTACAAGGTGTCCAACCGGTTCAGCGGCGT GCCCGATAGATTTTCTGGCTCTGGCAGCGGCACCGACTTCACCCTGAAGATCTCTAGAGTGGAAGCCG AGGACCTGGGCGTGTACTACTGCTTCCAAGGCAGCCACGTGCCAAGAACCTTTGGCGGCGGAACAAAG CTGGAACTGAAGCGGACACAGAGCCCCACACCATCTCCAACAGGACTGACCACCGCCAAGATGCCTAG CGTGCCCCTCTCTTCTGACCCTCTGCCTACACACACCACCGCTTTTAGCCCTGCCAGCACCTTCGAGA GAGAGAACGACTTCAGCGAGACAACCACCTCTCTGAGCCCCGACAACACCAGCACACAGGTGTCCCCA GACAGCCTGGATAATGCCAGCGCCTTCAATACCACCGGCGTGTCCTCTGTGCAGACCCCTCATCTGCC AACACACGCCGATAGCCAGACACCTTCTGCCGGCACCGATACACAGACCTTTTCTGGCTCTGCCGCCAAttorney Docket No. 44807-0518WO1 / P18835-01ACGCCAAGCTGAACCCTACACCTGGCAGCAACGCCATCTCTGATGTGCCTGGCGAGAGAAGCACCGCC AGCACATTTCCAACAGACCCCGTGTCTCCCCTGACCACCACACTGTCTCTGGCCCACCATAGCTCTGC TGCCCTGCCTGCCAGAACCAGCAACACCACCATCACCGCCAATACCAGCGACGCCTACCTGAACGCCA GCGAAACCACAACACTGAGCCCTAGCGGAAGCGCCGTGATCAGCACAACCACAATCGCCACCACACCT AGCAAGCCTACCTGCGACGAGAAGTACGCCAACATCACCGTGGACTACCTGTACAACAAAGAGACAAA GCTGTTCACGGCCAAGCTCAACGTGAACGAGAACGTGGAATGCGGCAACAATACCTGCACCAACAACG AGGTGCACAACCTGACCGAGTGCAAGAACGCCTCCGTGTCCATCAGCCACAACAGCTGCACAGCCCCT GACAAGACCCTGATCCTGGATGTGCCTCCTGGCGTGGAAAAGTTCCAGCTGCACGATTGCACCCAGGT GGAAAAGGCCGATACCACCATCTGCCTGAAGTGGAAGAACATCGAGACATTCACCTGTGACACCCAGA ACATCACCTACCGGTTCCAGTGCGGCAATATGATCTTCGATAACAAAGAAATCAAGCTCGAGAACCTC GAGCCTGAGCACGAGTACAAGTGCGACAGCGAGATCCTGTATAACAATCACAAGTTCACCAACGCCAG CAAGATCATCAAGACCGACTTCGGCTCTCCCGGCGAGCCCCAGATCATCTTCTGTAGATCTGAGGCCG CTCACCAGGGCGTGATCACCTGGAATCCTCCACAGCGGAGCTTCCACAACTTCACCCTGTGCTACATC AAAGAAACCGAGAAGGACTGCCTGAACCTGGACAAGAACCTCATTAAGTACGACCTGCAGAACCTGAA GCCGTACACCAAATACGTGCTGAGCCTGCACGCCTACATCATTGCCAAGGTGCAGAGAAATGGCAGCG CCGCCATGTGCCACTTCACCACAAAAAGCGCCCCTCCAAGCCAAGTGTGGAACATGACCGTGTCTATG ACCAGCGACAACTCCATGCACGTGAAGTGCCGGCCTCCACGGGATAGAAATGGCCCTCACGAGAGATA CCACCTGGAAGTCGAGGCCGGAAATACCCTCGTGCGGAACGAGAGCCACAAGAACTGCGACTTCAGAG TGAAGGACCTGCAGTACAGCACCGACTACACCTTCAAGGCCTACTTCCACAATGGCGACTACCCTGGC GAGCCCTTCATCCTGCACCACAGCACCAGCTACAACAGCAAGGCTCTCATTGCGTTTTTGGCTTTTCT GATTATTGTCACTAGTATCGCGCTTCTGGTAGTACTTCGAAAACGCAGACGAATGAAGCTGCTGAGCA GCATCGAGCAGGCCTGTGACATCTGCCGGCTGAAGAAACTGAAGTGCAGCAAAGAAAAGCCCAAGTGC GCCAAGTGCCTGAAGAACAACTGGGAGTGCCGGTACAGCCCCAAGACCAAGAGAAGCCCTCTGACAAG AGCCCACCTGACCGAGGTGGAAAGCCGGCTGGAAAGACTCGAGCAGCTGTTCCTGCTGATCTTCCCCA GAGAAGATCTGGACATGATCCTGAAGATGGACAGCCTGCAGGACATCAAGGCCCTGCTGACCGGACTG TTCGTGCAGGACAACGTGAACAAGGACGCCGTGACCGATAGACTGGCCAGCGTGGAAACCGACATGCC CCTGACACTGCGGCAGCACAGAATCAGCGCCACAAGCAGCAGCGAGGAAAGCAGCAACAAGGGCCAGA GACAGCTGACAGTGTCTGCTGCTGCTGGCGGAAGCGGAGGATCTGGTGGATCTGATGCCCTGGACGAC TTCGACCTGGATATGCTGGGCAGCGACGCCCTGGATGATTTCGATCTCGACATGCTCGGCTCCGACGC TCTCGACGACTTTGATTTGGACATGTTGGGCTCCGATGCACTTGATGATTTTGACTTGGATATGCTCG GAAGCCGGGCCAAACGATCTGGCTCTGGCCAGTGTACCAACTATGCCCTGCTCAAGCTCGCTGGCGAC GTCGAGTCTAACCCTGGACCAATGGGAGCTGGCGCTACAGGCAGAGCTATGGATGGACCTAGACTGCT GCTGCTCCTGCTTCTGGGAGTGTCTCTTGGCGGAGCCAAAGAGGCCTGTCCTACCGGCCTGTATACAC ACTCTGGCGAGTGCTGCAAGGCCTGCAATCTTGGAGAAGGCGTCGCACAGCCTTGCGGCGCTAATCAG ACAGTGTGCGAGCCTTGCCTGGACAGCGTGACCTTTAGCGACGTGGTGTCAGCCACCGAGCCATGCAA GCCATGTACCGAGTGTGTGGGCCTGCAGAGCATGTCTGCCCCTTGCGTGGAAGCTGACGATGCCGTGT GTAGATGCGCCTACGGCTACTACCAGGACGAGACAACAGGCAGATGCGAGGCCTGTAGAGTGTGCGAA GCTGGATCTGGCCTGGTGTTCAGCTGCCAAGACAAGCAGAACACCGTGTGCGAGGAATGCCCCGATGG CACCTATAGCGACGAGGCCAACCATGTGGATCCCTGCCTGCCTTGTACCGTGTGTGAAGATACCGAGC GGCAGCTGCGCGAGTGTACAAGATGGGCTGATGCCGAGTGCGAAGAGATCCCTGGCAGATGGATCACC AGAAGCACACCTCCAGAGGGCAGCGATAGCACAGCCCCTTCTACACAAGAGCCCGAGGCTCCTCCTGA GCAGGACCTGATTGCTTCTACAGTGGCTGGCGTCGTGACCACCGTGATGGGATCTAGTCAGCCCGTGG TCACCAGAGGCACCACCGACAATCTGATCCCCGTGTACTGTAGCATCCTGGCCGCCGTGGTTGTTGGA CTGGTGGCCTATATCGCCTTCAAGCGGTGGAACAGCTGA(SEQ ID NO: 102)Attorney Docket No. 44807-0518WO1 / P18835-01SNIPR-3 LVSmut DesignCD8a SP - myc tag - BB7.2 - CD45 ECD - CD45 TMD LVSmut - NOTCH1 JMD - Gal4DBD_VP64 TF - E2A - tNGFRAmino Acid Sequence for SNIPR-3 LVSmut MALPVTALLLPLALLLHAARPEQKLISEEDLQVQLQQSGPELVKPGASVKMSCKASGYTFTSYHIQWV KQRPGQGLEWIGWIYPGDGSTQYNEKFKGKTTLTADKSSSTAYMLLSSLTSEDSAIYFCAREGTYYAM DYWGQGTSVTVSSGGGGSGGGGSGGGGSDIVMTQAPLSLPVSLGDQVSISCRSSQSIVHSNGNTYLEW YLQKPGQSPKLLIYKVSNRFSGVPDRFSGSGSGTDFTLKISRVEAEDLGVYYCFQGSHVPRTFGGGTK LELKRTQSPTPSPTGLTTAKMPSVPLSSDPLPTHTTAFSPASTFERENDFSETTTSLSPDNTSTQVSP DSLDNASAFNTTGVSSVQTPHLPTHADSQTPSAGTDTQTFSGSAANAKLNPTPGSNAISDVPGERSTA STFPTDPVSPLTTTLSLAHHSSAALPARTSNTTITANTSDAYLNASETTTLSPSGSAVISTTTIATTP SKPTCDEKYANITVDYLYNKETKLFTAKLNVNENVECGNNTCTNNEVHNLTECKNASVSISHNSCTAP DKTLILDVPPGVEKFQLHDCTQVEKADTTICLKWKNIETFTCDTQNITYRFQCGNMIFDNKEIKLENL EPEHEYKCDSEILYNNHKFTNASKIIKTDFGSPGEPQIIFCRSEAAHQGVITWNPPQRSFHNFTLCYI KETEKDCLNLDKNLIKYDLQNLKPYTKYVLSLHAYIIAKVQRNGSAAMCHFTTKSAPPSQVWNMTVSM TSDNSMHVKCRPPRDRNGPHERYHLEVEAGNTLVRNESHKNCDFRVKDLQYSTDYTFKAYFHNGDYPG EPFILHHSTSYNSKALIAFLAFLIIVTSIALLGVLVSRKRRRMKLLSSIEQACDICRLKKLKCSKEKP KCAKCLKNNWECRYSPKTKRSPLTRAHLTEVESRLERLEQLFLLIFPREDLDMILKMDSLQDIKALLT GLFVQDNVNKDAVTDRLASVETDMPLTLRQHRISATSSSEESSNKGQRQLTVSAAAGGSGGSGGSDAL DDFDLDMLGSDALDDFDLDMLGSDALDDFDLDMLGSDALDDFDLDMLGSRAKRSGSGQCTNYALLKLA GDVESNPGPMGAGATGRAMDGPRLLLLLLLGVSLGGAKEACPTGLYTHSGECCKACNLGEGVAQPCGA NQTVCEPCLDSVTFSDVVSATEPCKPCTECVGLQSMSAPCVEADDAVCRCAYGYYQDETTGRCEACRV CEAGSGLVFSCQDKQNTVCEECPDGTYSDEANHVDPCLPCTVCEDTERQLRECTRWADAECEEIPGRW ITRSTPPEGSDSTAPSTQEPEAPPEQDLIASTVAGVVTTVMGSSQPVVTRGTTDNLIPVYCSILAAVV VGLVAY IAFKRWNS *(SEQ ID NO: 103)Nucleic Acid Sequence for SNIPR-3 LVSmut ATGGCTCTGCCTGTGACAGCTCTGCTGCTGCCTCTGGCTCTGCTTCTGCATGCCGCTAGACCTGAGCA GAAGCTGATCTCCGAAGAGGACCTGCAGGTTCAGCTGCAGCAGTCTGGACCTGAGCTGGTTAAGCCTG GCGCTTCCGTGAAGATGAGCTGCAAGGCCAGCGGCTACACCTTCACCAGCTACCACATCCAGTGGGTC AAGCAGAGGCCTGGACAGGGACTCGAGTGGATCGGCTGGATCTATCCTGGCGACGGCAGCACCCAGTA CAACGAGAAGTTCAAGGGCAAGACCACACTGACCGCCGACAAGAGCAGCAGCACAGCCTACATGCTGC TGAGCAGCCTGACCAGCGAGGACAGCGCCATCTACTTTTGTGCCAGAGAGGGCACCTACTACGCCATG GATTATTGGGGCCAGGGCACCAGCGTGACAGTCTCTTCTGGTGGCGGAGGATCTGGCGGAGGTGGAAG CGGCGGAGGCGGATCTGATATCGTGATGACACAGGCCCCTCTGAGCCTGCCTGTGTCTCTGGGAGATC AGGTGTCCATCAGCTGTCGGAGCAGCCAGAGCATCGTGCACAGCAACGGCAACACCTACCTGGAATGG TATCTGCAGAAGCCCGGACAGAGCCCCAAGCTGCTGATCTACAAGGTGTCCAACCGGTTCAGCGGCGT GCCCGATAGATTTTCTGGCTCTGGCAGCGGCACCGACTTCACCCTGAAGATCTCTAGAGTGGAAGCCG AGGACCTGGGCGTGTACTACTGCTTCCAAGGCAGCCACGTGCCAAGAACCTTTGGCGGCGGAACAAAG CTGGAACTGAAGCGGACACAGAGCCCCACACCATCTCCAACAGGACTGACCACCGCCAAGATGCCTAG CGTGCCCCTCTCTTCTGACCCTCTGCCTACACACACCACCGCTTTTAGCCCTGCCAGCACCTTCGAGA GAGAGAACGACTTCAGCGAGACAACCACCTCTCTGAGCCCCGACAACACCAGCACACAGGTGTCCCCA GACAGCCTGGATAATGCCAGCGCCTTCAATACCACCGGCGTGTCCTCTGTGCAGACCCCTCATCTGCC AACACACGCCGATAGCCAGACACCTTCTGCCGGCACCGATACACAGACCTTTTCTGGCTCTGCCGCCAAttorney Docket No. 44807-0518WO1 / P18835-01ACGCCAAGCTGAACCCTACACCTGGCAGCAACGCCATCTCTGATGTGCCTGGCGAGAGAAGCACCGCC AGCACATTTCCAACAGACCCCGTGTCTCCCCTGACCACCACACTGTCTCTGGCCCACCATAGCTCTGC TGCCCTGCCTGCCAGAACCAGCAACACCACCATCACCGCCAATACCAGCGACGCCTACCTGAACGCCA GCGAAACCACAACACTGAGCCCTAGCGGAAGCGCCGTGATCAGCACAACCACAATCGCCACCACACCT AGCAAGCCTACCTGCGACGAGAAGTACGCCAACATCACCGTGGACTACCTGTACAACAAAGAGACAAA GCTGTTCACGGCCAAGCTCAACGTGAACGAGAACGTGGAATGCGGCAACAATACCTGCACCAACAACG AGGTGCACAACCTGACCGAGTGCAAGAACGCCTCCGTGTCCATCAGCCACAACAGCTGCACAGCCCCT GACAAGACCCTGATCCTGGATGTGCCTCCTGGCGTGGAAAAGTTCCAGCTGCACGATTGCACCCAGGT GGAAAAGGCCGATACCACCATCTGCCTGAAGTGGAAGAACATCGAGACATTCACCTGTGACACCCAGA ACATCACCTACCGGTTCCAGTGCGGCAATATGATCTTCGATAACAAAGAAATCAAGCTCGAGAACCTC GAGCCTGAGCACGAGTACAAGTGCGACAGCGAGATCCTGTATAACAATCACAAGTTCACCAACGCCAG CAAGATCATCAAGACCGACTTCGGCTCTCCCGGCGAGCCCCAGATCATCTTCTGTAGATCTGAGGCCG CTCACCAGGGCGTGATCACCTGGAATCCTCCACAGCGGAGCTTCCACAACTTCACCCTGTGCTACATC AAAGAAACCGAGAAGGACTGCCTGAACCTGGACAAGAACCTCATTAAGTACGACCTGCAGAACCTGAA GCCGTACACCAAATACGTGCTGAGCCTGCACGCCTACATCATTGCCAAGGTGCAGAGAAATGGCAGCG CCGCCATGTGCCACTTCACCACAAAAAGCGCCCCTCCAAGCCAAGTGTGGAACATGACCGTGTCTATG ACCAGCGACAACTCCATGCACGTGAAGTGCCGGCCTCCACGGGATAGAAATGGCCCTCACGAGAGATA CCACCTGGAAGTCGAGGCCGGAAATACCCTCGTGCGGAACGAGAGCCACAAGAACTGCGACTTCAGAG TGAAGGACCTGCAGTACAGCACCGACTACACCTTCAAGGCCTACTTCCACAATGGCGACTACCCTGGC GAGCCCTTCATCCTGCACCACAGCACCAGCTACAACAGCAAGGCACTGATTGCGTTCCTGGCTTTTTT GATCATTGTCACCAGTATAGCACTTCTCGGAGTTCTTGTGTCCAGAAAGAGACGAAGAATGAAGCTGC TGAGCAGCATCGAGCAGGCCTGTGACATCTGCCGGCTGAAGAAACTGAAGTGCAGCAAAGAAAAGCCC AAGTGCGCCAAGTGCCTGAAGAACAACTGGGAGTGCCGGTACAGCCCCAAGACCAAGAGAAGCCCTCT GACAAGAGCCCACCTGACCGAGGTGGAAAGCCGGCTGGAAAGACTCGAGCAGCTGTTCCTGCTGATCT TCCCCAGAGAAGATCTGGACATGATCCTGAAGATGGACAGCCTGCAGGACATCAAGGCCCTGCTGACC GGACTGTTCGTGCAGGACAACGTGAACAAGGACGCCGTGACCGATAGACTGGCCAGCGTGGAAACCGA CATGCCCCTGACACTGCGGCAGCACAGAATCAGCGCCACAAGCAGCAGCGAGGAAAGCAGCAACAAGG GCCAGAGACAGCTGACAGTGTCTGCTGCTGCTGGCGGAAGCGGAGGATCTGGTGGATCTGATGCCCTG GACGACTTCGACCTGGATATGCTGGGCAGCGACGCCCTGGATGATTTCGATCTCGACATGCTCGGCTC CGACGCTCTCGACGACTTTGATTTGGACATGTTGGGCTCCGATGCACTTGATGATTTTGACTTGGATA TGCTCGGAAGCCGGGCCAAACGATCTGGCTCTGGCCAGTGTACCAACTATGCCCTGCTCAAGCTCGCT GGCGACGTCGAGTCTAACCCTGGACCAATGGGAGCTGGCGCTACAGGCAGAGCTATGGATGGACCTAG ACTGCTGCTGCTCCTGCTTCTGGGAGTGTCTCTTGGCGGAGCCAAAGAGGCCTGTCCTACCGGCCTGT ATACACACTCTGGCGAGTGCTGCAAGGCCTGCAATCTTGGAGAAGGCGTCGCACAGCCTTGCGGCGCT AATCAGACAGTGTGCGAGCCTTGCCTGGACAGCGTGACCTTTAGCGACGTGGTGTCAGCCACCGAGCC ATGCAAGCCATGTACCGAGTGTGTGGGCCTGCAGAGCATGTCTGCCCCTTGCGTGGAAGCTGACGATG CCGTGTGTAGATGCGCCTACGGCTACTACCAGGACGAGACAACAGGCAGATGCGAGGCCTGTAGAGTG TGCGAAGCTGGATCTGGCCTGGTGTTCAGCTGCCAAGACAAGCAGAACACCGTGTGCGAGGAATGCCC CGATGGCACCTATAGCGACGAGGCCAACCATGTGGATCCCTGCCTGCCTTGTACCGTGTGTGAAGATA CCGAGCGGCAGCTGCGCGAGTGTACAAGATGGGCTGATGCCGAGTGCGAAGAGATCCCTGGCAGATGG ATCACCAGAAGCACACCTCCAGAGGGCAGCGATAGCACAGCCCCTTCTACACAAGAGCCCGAGGCTCC TCCTGAGCAGGACCTGATTGCTTCTACAGTGGCTGGCGTCGTGACCACCGTGATGGGATCTAGTCAGC CCGTGGTCACCAGAGGCACCACCGACAATCTGATCCCCGTGTACTGTAGCATCCTGGCCGCCGTGGTT GTTGGACTGGTGGCCTATATCGCCTTCAAGCGGTGGAACAGCTGA(SEQ ID NO: 104)Attorney Docket No. 44807-0518WO1 / P18835-01SNIPR-4 DesignCD8a SP - myc tag - BB7.2 - CD45 ECD - murine NOTCH1 NRR- NOTCH1 TMD - NOTCH2 JMD - Gal4DBD VP64 TF - E2A - tNGFRAmino Acid Sequence for SNIPR-4 MALPVTALLLPLALLLHAARPEQKLISEEDLQVQLQQSGPELVKPGASVKMSCKASGYTFTSYHIQWV KQRPGQGLEWIGWIYPGDGSTQYNEKFKGKTTLTADKSSSTAYMLLSSLTSEDSAIYFCAREGTYYAM DYWGQGTSVTVSSGGGGSGGGGSGGGGSDIVMTQAPLSLPVSLGDQVSISCRSSQSIVHSNGNTYLEW YLQKPGQSPKLLIYKVSNRFSGVPDRFSGSGSGTDFTLKISRVEAEDLGVYYCFQGSHVPRTFGGGTK LELKRTQSPTPSPTGLTTAKMPSVPLSSDPLPTHTTAFSPASTFERENDFSETTTSLSPDNTSTQVSP DSLDNASAFNTTGVSSVQTPHLPTHADSQTPSAGTDTQTFSGSAANAKLNPTPGSNAISDVPGERSTA STFPTDPVSPLTTTLSLAHHSSAALPARTSNTTITANTSDAYLNASETTTLSPSGSAVISTTTIATTP SKPTCDEKYANITVDYLYNKETKLFTAKLNVNENVECGNNTCTNNEVHNLTECKNASVSISHNSCTAP DKTLILDVPPGVEKFQLHDCTQVEKADTTICLKWKNIETFTCDTQNITYRFQCGNMIFDNKEIKLENL EPEHEYKCDSEILYNNHKFTNASKIIKTDFGSPGEPQIIFCRSEAAHQGVITWNPPQRSFHNFTLCYI KETEKDCLNLDKNLIKYDLQNLKPYTKYVLSLHAYIIAKVQRNGSAAMCHFTTKSAPPSQVWNMTVSM TSDNSMHVKCRPPRDRNGPHERYHLEVEAGNTLVRNESHKNCDFRVKDLQYSTDYTFKAYFHNGDYPG EPFILHHSTSYNSKILDYSFTGGAGRDIPPPQIEEACELPECQVDAGNKVCNLQCNNHACGWDGGDCS LNFNDPWKNCTQSLQCWKYFSDGHCDSQCNSAGCLFDGFDCQLTEGQCNPLYDQYCKDHFSDGHCDQG CNSAECEWDGLDCAEHVPERLAAGTLVLVVLLPPDQLRNNSFHFLRELSHVLHTNVVFKRDAQGQQMI FPYYGHEEELRKHPIKRSTVGWATSSLLPGTSGGRQRRELDPMDIRGSIVYLEIDNRQCVQSSSQCFQ SATDVAAFLGALASLGSLNIPYKIEAVKSEPVEPPLPSQFMYVAAAAFVLLFFVGCGVLLSKRKRKHM KLLSSIEQACDICRLKKLKCSKEKPKCAKCLKNNWECRYSPKTKRSPLTRAHLTEVESRLERLEQLFL LIFPREDLDMILKMDSLQDIKALLTGLFVQDNVNKDAVTDRLASVETDMPLTLRQHRISATSSSEESS NKGQRQLTVSAAAGGSGGSGGSDALDDFDLDMLGSDALDDFDLDMLGSDALDDFDLDMLGSDALDDFD LDMLGSRAKRSGSGQCTNYALLKLAGDVESNPGPMGAGATGRAMDGPRLLLLLLLGVSLGGAKEACPT GLYTHSGECCKACNLGEGVAQPCGANQTVCEPCLDSVTFSDVVSATEPCKPCTECVGLQSMSAPCVEA DDAVCRCAYGYYQDETTGRCEACRVCEAGSGLVFSCQDKQNTVCEECPDGTYSDEANHVDPCLPCTVC EDTERQLRECTRWADAECEEIPGRWITRSTPPEGSDSTAPSTQEPEAPPEQDLIASTVAGVVTTVMGS SQPVVTRGTTDNLIPVYCSI L AAV V VGL VA Y IAFKRWNS*(SEQ ID NO: 105)Nucleic Acid Sequence for SNIPR-4 ATGGCTCTGCCTGTGACAGCTCTGCTGCTGCCTCTGGCTCTGCTTCTGCATGCCGCTAGACCTGAGCA GAAGCTGATCTCCGAAGAGGACCTGCAGGTTCAGCTGCAGCAGTCTGGACCTGAGCTGGTTAAGCCTG GCGCTTCCGTGAAGATGAGCTGCAAGGCCAGCGGCTACACCTTCACCAGCTACCACATCCAGTGGGTC AAGCAGAGGCCTGGACAGGGACTCGAGTGGATCGGCTGGATCTATCCTGGCGACGGCAGCACCCAGTA CAACGAGAAGTTCAAGGGCAAGACCACACTGACCGCCGACAAGAGCAGCAGCACAGCCTACATGCTGC TGAGCAGCCTGACCAGCGAGGACAGCGCCATCTACTTTTGTGCCAGAGAGGGCACCTACTACGCCATG GATTATTGGGGCCAGGGCACCAGCGTGACAGTCTCTTCTGGTGGCGGAGGATCTGGCGGAGGTGGAAG CGGCGGAGGCGGATCTGATATCGTGATGACACAGGCCCCTCTGAGCCTGCCTGTGTCTCTGGGAGATC AGGTGTCCATCAGCTGTCGGAGCAGCCAGAGCATCGTGCACAGCAACGGCAACACCTACCTGGAATGG TATCTGCAGAAGCCCGGACAGAGCCCCAAGCTGCTGATCTACAAGGTGTCCAACCGGTTCAGCGGCGT GCCCGATAGATTTTCTGGCTCTGGCAGCGGCACCGACTTCACCCTGAAGATCTCTAGAGTGGAAGCCG AGGACCTGGGCGTGTACTACTGCTTCCAAGGCAGCCACGTGCCAAGAACCTTTGGCGGCGGAACAAAG CTGGAACTGAAGCGGACACAGAGCCCCACACCATCTCCAACAGGACTGACCACCGCCAAGATGCCTAGAttorney Docket No. 44807-0518WO1 / P18835-01CGTGCCCCTCTCTTCTGACCCTCTGCCTACACACACCACCGCTTTTAGCCCTGCCAGCACCTTCGAGA GAGAGAACGACTTCAGCGAGACAACCACCTCTCTGAGCCCCGACAACACCAGCACACAGGTGTCCCCA GACAGCCTGGATAATGCCAGCGCCTTCAATACCACCGGCGTGTCCTCTGTGCAGACCCCTCATCTGCC AACACACGCCGATAGCCAGACACCTTCTGCCGGCACCGATACACAGACCTTTTCTGGCTCTGCCGCCA ACGCCAAGCTGAACCCTACACCTGGCAGCAACGCCATCTCTGATGTGCCTGGCGAGAGAAGCACCGCC AGCACATTTCCAACAGACCCCGTGTCTCCCCTGACCACCACACTGTCTCTGGCCCACCATAGCTCTGC TGCCCTGCCTGCCAGAACCAGCAACACCACCATCACCGCCAATACCAGCGACGCCTACCTGAACGCCA GCGAAACCACAACACTGAGCCCTAGCGGAAGCGCCGTGATCAGCACAACCACAATCGCCACCACACCT AGCAAGCCTACCTGCGACGAGAAGTACGCCAACATCACCGTGGACTACCTGTACAACAAAGAGACAAA GCTGTTCACGGCCAAGCTCAACGTGAACGAGAACGTGGAATGCGGCAACAATACCTGCACCAACAACG AGGTGCACAACCTGACCGAGTGCAAGAACGCCTCCGTGTCCATCAGCCACAACAGCTGCACAGCCCCT GACAAGACCCTGATCCTGGATGTGCCTCCTGGCGTGGAAAAGTTCCAGCTGCACGATTGCACCCAGGT GGAAAAGGCCGATACCACCATCTGCCTGAAGTGGAAGAACATCGAGACATTCACCTGTGACACCCAGA ACATCACCTACCGGTTCCAGTGCGGCAATATGATCTTCGATAACAAAGAAATCAAGCTCGAGAACCTC GAGCCTGAGCACGAGTACAAGTGCGACAGCGAGATCCTGTATAACAATCACAAGTTCACCAACGCCAG CAAGATCATCAAGACCGACTTCGGCTCTCCCGGCGAGCCCCAGATCATCTTCTGTAGATCTGAGGCCG CTCACCAGGGCGTGATCACCTGGAATCCTCCACAGCGGAGCTTCCACAACTTCACCCTGTGCTACATC AAAGAAACCGAGAAGGACTGCCTGAACCTGGACAAGAACCTCATTAAGTACGACCTGCAGAACCTGAA GCCGTACACCAAATACGTGCTGAGCCTGCACGCCTACATCATTGCCAAGGTGCAGAGAAATGGCAGCG CCGCCATGTGCCACTTCACCACAAAAAGCGCCCCTCCAAGCCAAGTGTGGAACATGACCGTGTCTATG ACCAGCGACAACTCCATGCACGTGAAGTGCCGGCCTCCACGGGATAGAAATGGCCCTCACGAGAGATA CCACCTGGAAGTCGAGGCCGGAAATACCCTCGTGCGGAACGAGAGCCACAAGAACTGCGACTTCAGAG TGAAGGACCTGCAGTACAGCACCGACTACACCTTCAAGGCCTACTTCCACAATGGCGACTACCCTGGC GAGCCCTTCATCCTGCACCACAGCACCAGCTACAACAGCAAGATCCTGGACTACAGCTTCACCGGCGG AGCCGGCAGAGATATTCCTCCACCTCAGATCGAGGAAGCCTGCGAGCTGCCTGAGTGTCAAGTGGACG CCGGCAACAAAGTGTGCAACCTGCAGTGCAACAACCACGCCTGTGGATGGGATGGCGGCGACTGCAGC CTGAACTTCAACGACCCCTGGAAGAACTGCACCCAGAGCCTGCAGTGTTGGAAGTACTTTAGCGACGG CCACTGCGACAGCCAGTGTAATTCTGCCGGATGCCTGTTCGACGGCTTCGACTGCCAACTGACAGAGG GCCAGTGCAACCCTCTGTACGACCAGTACTGCAAGGACCACTTCTCCGATGGCCACTGTGACCAGGGC TGTAATAGCGCCGAGTGCGAGTGGGATGGACTGGATTGTGCCGAGCACGTGCCAGAAAGACTGGCCGC TGGAACACTGGTGCTGGTTGTTCTGCTGCCTCCTGACCAGCTGCGGAACAACAGCTTCCACTTCCTGC GGGAACTGAGCCACGTGCTGCACACCAACGTGGTGTTCAAGAGAGATGCCCAGGGCCAGCAGATGATC TTCCCCTACTATGGCCACGAAGAGGAACTGCGGAAGCACCCCATCAAGAGAAGCACAGTTGGCTGGGC CACCAGCTCACTGCTGCCTGGAACATCTGGCGGCAGACAGAGAAGAGAACTGGACCCCATGGACATCC GGGGCAGCATCGTGTACCTGGAAATCGACAACCGGCAGTGCGTGCAGAGCAGCAGCCAGTGCTTTCAG AGCGCTACAGATGTGGCCGCCTTTCTGGGAGCACTGGCATCTCTGGGCTCCCTGAACATCCCCTACAA GATCGAGGCCGTGAAGTCCGAGCCTGTGGAACCTCCATTGCCTAGCCAGTTTATGTACGTGGCCGCTG CTGCCTTCGTGCTGCTGTTCTTTGTTGGCTGCGGAGTGCTGCTGAGCAAGCGGAAGAGAAAGCACATG AAGCTGCTGAGCAGCATCGAGCAGGCCTGTGACATCTGCCGGCTGAAGAAACTGAAGTGCAGCAAAGA AAAGCCCAAGTGCGCCAAGTGCCTGAAGAACAACTGGGAGTGCCGGTACAGCCCCAAGACCAAGAGAA GCCCTCTGACAAGAGCCCACCTGACCGAGGTGGAAAGCCGGCTGGAAAGACTCGAGCAGCTGTTCCTG CTGATCTTCCCCAGAGAAGATCTGGACATGATCCTGAAGATGGACAGCCTGCAGGACATCAAGGCCCT GCTGACCGGACTGTTCGTGCAGGACAACGTGAACAAGGACGCCGTGACCGATAGACTGGCCAGCGTGG AAACCGACATGCCCCTGACACTGCGGCAGCACAGAATCAGCGCCACAAGCAGCAGCGAGGAAAGCAGC AACAAGGGCCAGAGACAGCTGACAGTGTCTGCTGCTGCTGGCGGAAGCGGAGGATCTGGTGGATCTGA TGCCCTGGACGACTTCGACCTGGATATGCTGGGCAGCGACGCCCTGGATGATTTCGATCTCGACATGC TCGGCTCCGACGCTCTCGACGACTTTGATTTGGACATGTTGGGCTCCGATGCACTTGATGATTTTGAC TTGGATATGCTCGGAAGCCGGGCCAAACGATCTGGCTCTGGCCAGTGTACCAACTATGCCCTGCTCAA GCTCGCTGGCGACGTCGAGTCTAACCCTGGACCAATGGGAGCTGGCGCTACAGGCAGAGCTATGGATGAttorney Docket No. 44807-0518WO1 / P18835-01GACCTAGACTGCTGCTGCTCCTGCTTCTGGGAGTGTCTCTTGGCGGAGCCAAAGAGGCCTGTCCTACC GGCCTGTATACACACTCTGGCGAGTGCTGCAAGGCCTGCAATCTTGGAGAAGGCGTCGCACAGCCTTG CGGCGCTAATCAGACAGTGTGCGAGCCTTGCCTGGACAGCGTGACCTTTAGCGACGTGGTGTCAGCCA CCGAGCCATGCAAGCCATGTACCGAGTGTGTGGGCCTGCAGAGCATGTCTGCCCCTTGCGTGGAAGCT GACGATGCCGTGTGTAGATGCGCCTACGGCTACTACCAGGACGAGACAACAGGCAGATGCGAGGCCTG TAGAGTGTGCGAAGCTGGATCTGGCCTGGTGTTCAGCTGCCAAGACAAGCAGAACACCGTGTGCGAGG AATGCCCCGATGGCACCTATAGCGACGAGGCCAACCATGTGGATCCCTGCCTGCCTTGTACCGTGTGT GAAGATACCGAGCGGCAGCTGCGCGAGTGTACAAGATGGGCTGATGCCGAGTGCGAAGAGATCCCTGG CAGATGGATCACCAGAAGCACACCTCCAGAGGGCAGCGATAGCACAGCCCCTTCTACACAAGAGCCCG AGGCTCCTCCTGAGCAGGACCTGATTGCTTCTACAGTGGCTGGCGTCGTGACCACCGTGATGGGATCT AGTCAGCCCGTGGTCACCAGAGGCACCACCGACAATCTGATCCCCGTGTACTGTAGCATCCTGGCCGC CGTGGTTGTTGGACTGGTGGCCTATATCGCCTTCAAGCGGTGGAACAGCTGA(SEQ ID NO: 106)SNIPR-4 RAM7 DesignCD8a SP - myc tag - BB7.2 - CD45 ECD - murine NOTCH1 NRR- NOTCH1 TMD - NOTCH2 JMD - RAM7 - Gal4DBD_VP64 TF - E2A - tNGFRAmino Acid Sequence for SNIPR-4 RAM7 MALPVTALLLPLALLLHAARPEQKLISEEDLQVQLQQSGPELVKPGASVKMSCKASGYTFTSYHIQWV KQRPGQGLEWIGWIYPGDGSTQYNEKFKGKTTLTADKSSSTAYMLLSSLTSEDSAIYFCAREGTYYAM DYWGQGTSVTVSSGGGGSGGGGSGGGGSDIVMTQAPLSLPVSLGDQVSISCRSSQSIVHSNGNTYLEW YLQKPGQSPKLLIYKVSNRFSGVPDRFSGSGSGTDFTLKISRVEAEDLGVYYCFQGSHVPRT FGGGTK LELKRTQSPTPSPTGLTTAKMPSVPLSSDPLPTHTTAFSPASTFERENDFSETTTSLSPDNTSTQVSP DSLDNASAFNTTGVSSVQTPHLPTHADSQTPSAGTDTQTFSGSAANAKLNPTPGSNAISDVPGERSTA STFPTDPVSPLTTTLSLAHHSSAALPARTSNTTITANTSDAYLNASETTTLSPSGSAVISTTTIATTP SKPTCDEKYANITVDYLYNKETKLFTAKLNVNENVECGNNTCTNNEVHNLTECKNASVSISHNSCTAP DKTLILDVPPGVEKFQLHDCTQVEKADTTICLKWKNIETFTCDTQNITYRFQCGNMIFDNKEIKLENL EPEHEYKCDSEILYNNHKFTNASKIIKTDFGSPGEPQIIFCRSEAAHQGVITWNPPQRSFHNFTLCYI KETEKDCLNLDKNLIKYDLQNLKPYTKYVLSLHAYIIAKVQRNGSAAMCHFTTKSAPPSQVWNMTVSM TSDNSMHVKCRPPRDRNGPHERYHLEVEAGNTLVRNESHKNCDFRVKDLQYSTDYTFKAYFHNGDYPG EPFILHHSTSYNSKILDYSFTGGAGRDIPPPQIEEACELPECQVDAGNKVCNLQCNNHACGWDGGDCS LNFNDPWKNCTQSLQCWKYFSDGHCDSQCNSAGCLFDGFDCQLTEGQCNPLYDQYCKDHFSDGHCDQG CNSAECEWDGLDCAEHVPERLAAGTLVLVVLLPPDQLRNNSFHFLRELSHVLHTNVVFKRDAQGQQMI FPYYGHEEELRKHPIKRSTVGWATSSLLPGTSGGRQRRELDPMDIRGSIVYLEIDNRQCVQSSSQCFQ SATDVAAFLGALASLGSLNIPYKIEAVKSEPVEPPLPSQFMYVAAAAFVLLFFVGCGVLLSKRKRKHQ HGQLWFMKLLSSIEQACDICRLKKLKCSKEKPKCAKCLKNNWECRYSPKTKRSPLTRAHLTEVESRLE RLEQLFLLIFPREDLDMILKMDSLQDIKALLTGLFVQDNVNKDAVTDRLASVETDMPLTLRQHRISAT SSSEESSNKGQRQLTVSAAAGGSGGSGGSDALDDFDLDMLGSDALDDFDLDMLGSDALDDFDLDMLGS DALDDFDLDMLGSRAKRSGSGQCTNYALLKLAGDVESNPGPMGAGATGRAMDGPRLLLLLLLGVSLGG AKEACPTGLYTHSGECCKACNLGEGVAQPCGANQTVCEPCLDSVTFSDVVSATEPCKPCTECVGLQSM SAPCVEADDAVCRCAYGYYQDETTGRCEACRVCEAGSGLVFSCQDKQNTVCEECPDGTYSDEANHVDP CLPCTVCEDTERQLRECTRWADAECEEIPGRWITRSTPPEGSDSTAPSTQEPEAPPEQDLIASTVAGV VTTVMGSSQPVVTRGTTDNLI PVYCS ILAAVVVGLVAY I FKRWNS *(SEQ ID NO: 107)Attorney Docket No. 44807-0518WO1 / P18835-01Nucleic Acid Sequence for SNIPR-4 RAM7 ATGGCTCTGCCTGTGACAGCTCTGCTGCTGCCTCTGGCTCTGCTTCTGCATGCCGCTAGACCTGAGCA GAAGCTGATCTCCGAAGAGGACCTGCAGGTTCAGCTGCAGCAGTCTGGACCTGAGCTGGTTAAGCCTG GCGCTTCCGTGAAGATGAGCTGCAAGGCCAGCGGCTACACCTTCACCAGCTACCACATCCAGTGGGTC AAGCAGAGGCCTGGACAGGGACTCGAGTGGATCGGCTGGATCTATCCTGGCGACGGCAGCACCCAGTA CAACGAGAAGTTCAAGGGCAAGACCACACTGACCGCCGACAAGAGCAGCAGCACAGCCTACATGCTGC TGAGCAGCCTGACCAGCGAGGACAGCGCCATCTACTTTTGTGCCAGAGAGGGCACCTACTACGCCATG GATTATTGGGGCCAGGGCACCAGCGTGACAGTCTCTTCTGGTGGCGGAGGATCTGGCGGAGGTGGAAG CGGCGGAGGCGGATCTGATATCGTGATGACACAGGCCCCTCTGAGCCTGCCTGTGTCTCTGGGAGATC AGGTGTCCATCAGCTGTCGGAGCAGCCAGAGCATCGTGCACAGCAACGGCAACACCTACCTGGAATGG TATCTGCAGAAGCCCGGACAGAGCCCCAAGCTGCTGATCTACAAGGTGTCCAACCGGTTCAGCGGCGT GCCCGATAGATTTTCTGGCTCTGGCAGCGGCACCGACTTCACCCTGAAGATCTCTAGAGTGGAAGCCG AGGACCTGGGCGTGTACTACTGCTTCCAAGGCAGCCACGTGCCAAGAACCTTTGGCGGCGGAACAAAG CTGGAACTGAAGCGGACACAGAGCCCCACACCATCTCCAACAGGACTGACCACCGCCAAGATGCCTAG CGTGCCCCTCTCTTCTGACCCTCTGCCTACACACACCACCGCTTTTAGCCCTGCCAGCACCTTCGAGA GAGAGAACGACTTCAGCGAGACAACCACCTCTCTGAGCCCCGACAACACCAGCACACAGGTGTCCCCA GACAGCCTGGATAATGCCAGCGCCTTCAATACCACCGGCGTGTCCTCTGTGCAGACCCCTCATCTGCC AACACACGCCGATAGCCAGACACCTTCTGCCGGCACCGATACACAGACCTTTTCTGGCTCTGCCGCCA ACGCCAAGCTGAACCCTACACCTGGCAGCAACGCCATCTCTGATGTGCCTGGCGAGAGAAGCACCGCC AGCACATTTCCAACAGACCCCGTGTCTCCCCTGACCACCACACTGTCTCTGGCCCACCATAGCTCTGC TGCCCTGCCTGCCAGAACCAGCAACACCACCATCACCGCCAATACCAGCGACGCCTACCTGAACGCCA GCGAAACCACAACACTGAGCCCTAGCGGAAGCGCCGTGATCAGCACAACCACAATCGCCACCACACCT AGCAAGCCTACCTGCGACGAGAAGTACGCCAACATCACCGTGGACTACCTGTACAACAAAGAGACAAA GCTGTTCACGGCCAAGCTCAACGTGAACGAGAACGTGGAATGCGGCAACAATACCTGCACCAACAACG AGGTGCACAACCTGACCGAGTGCAAGAACGCCTCCGTGTCCATCAGCCACAACAGCTGCACAGCCCCT GACAAGACCCTGATCCTGGATGTGCCTCCTGGCGTGGAAAAGTTCCAGCTGCACGATTGCACCCAGGT GGAAAAGGCCGATACCACCATCTGCCTGAAGTGGAAGAACATCGAGACATTCACCTGTGACACCCAGA ACATCACCTACCGGTTCCAGTGCGGCAATATGATCTTCGATAACAAAGAAATCAAGCTCGAGAACCTC GAGCCTGAGCACGAGTACAAGTGCGACAGCGAGATCCTGTATAACAATCACAAGTTCACCAACGCCAG CAAGATCATCAAGACCGACTTCGGCTCTCCCGGCGAGCCCCAGATCATCTTCTGTAGATCTGAGGCCG CTCACCAGGGCGTGATCACCTGGAATCCTCCACAGCGGAGCTTCCACAACTTCACCCTGTGCTACATC AAAGAAACCGAGAAGGACTGCCTGAACCTGGACAAGAACCTCATTAAGTACGACCTGCAGAACCTGAA GCCGTACACCAAATACGTGCTGAGCCTGCACGCCTACATCATTGCCAAGGTGCAGAGAAATGGCAGCG CCGCCATGTGCCACTTCACCACAAAAAGCGCCCCTCCAAGCCAAGTGTGGAACATGACCGTGTCTATG ACCAGCGACAACTCCATGCACGTGAAGTGCCGGCCTCCACGGGATAGAAATGGCCCTCACGAGAGATA CCACCTGGAAGTCGAGGCCGGAAATACCCTCGTGCGGAACGAGAGCCACAAGAACTGCGACTTCAGAG TGAAGGACCTGCAGTACAGCACCGACTACACCTTCAAGGCCTACTTCCACAATGGCGACTACCCTGGC GAGCCCTTCATCCTGCACCACAGCACCAGCTACAACAGCAAGATCCTGGACTACAGCTTCACCGGCGG AGCCGGCAGAGATATTCCTCCACCTCAGATCGAGGAAGCCTGCGAGCTGCCTGAGTGTCAAGTGGACG CCGGCAACAAAGTGTGCAACCTGCAGTGCAACAACCACGCCTGTGGATGGGATGGCGGCGACTGCAGC CTGAACTTCAACGACCCCTGGAAGAACTGCACCCAGAGCCTGCAGTGTTGGAAGTACTTTAGCGACGG CCACTGCGACAGCCAGTGTAATTCTGCCGGATGCCTGTTCGACGGCTTCGACTGCCAACTGACAGAGG GCCAGTGCAACCCTCTGTACGACCAGTACTGCAAGGACCACTTCTCCGATGGCCACTGTGACCAGGGC TGTAATAGCGCCGAGTGCGAGTGGGATGGACTGGATTGTGCCGAGCACGTGCCAGAAAGACTGGCCGC TGGAACACTGGTGCTGGTTGTTCTGCTGCCTCCTGACCAGCTGCGGAACAACAGCTTCCACTTCCTGC GGGAACTGAGCCACGTGCTGCACACCAACGTGGTGTTCAAGAGAGATGCCCAGGGCCAGCAGATGATC TTCCCCTACTATGGCCACGAAGAGGAACTGCGGAAGCACCCCATCAAGAGAAGCACAGTTGGCTGGGC CACCAGCTCACTGCTGCCTGGAACATCTGGCGGCAGACAGAGAAGAGAACTGGACCCCATGGACATCC GGGGCAGCATCGTGTACCTGGAAATCGACAACCGGCAGTGCGTGCAGAGCAGCAGCCAGTGCTTTCAGAttorney Docket No. 44807-0518WO1 / P18835-01AGCGCTACAGATGTGGCCGCCTTTCTGGGAGCACTGGCATCTCTGGGCTCCCTGAACATCCCCTACAA GATCGAGGCCGTGAAGTCCGAGCCTGTGGAACCTCCATTGCCTAGCCAGTTTATGTACGTGGCCGCTG CTGCCTTCGTGCTGCTGTTCTTTGTTGGCTGCGGAGTGCTGCTGAGCAAGCGGAAGAGAAAGCACCAG CATGGCCAGCTGTGGTTCATGAAGCTGCTGAGCAGCATCGAGCAGGCCTGTGACATCTGCCGGCTGAA GAAACTGAAGTGCAGCAAAGAAAAGCCCAAGTGCGCCAAGTGCCTGAAGAACAACTGGGAGTGCCGGT ACAGCCCCAAGACCAAGAGAAGCCCTCTGACAAGAGCCCACCTGACCGAGGTGGAAAGCCGGCTGGAA AGACTCGAGCAGCTGTTCCTGCTGATCTTCCCCAGAGAAGATCTGGACATGATCCTGAAGATGGACAG CCTGCAGGACATCAAGGCCCTGCTGACCGGACTGTTCGTGCAGGACAACGTGAACAAGGACGCCGTGA CCGATAGACTGGCCAGCGTGGAAACCGACATGCCCCTGACACTGCGGCAGCACAGAATCAGCGCCACA AGCAGCAGCGAGGAAAGCAGCAACAAGGGCCAGAGACAGCTGACAGTGTCTGCTGCTGCTGGCGGAAG CGGAGGATCTGGTGGATCTGATGCCCTGGACGACTTCGACCTGGATATGCTGGGCAGCGACGCCCTGG ATGATTTCGATCTCGACATGCTCGGCTCCGACGCTCTCGACGACTTTGATTTGGACATGTTGGGCTCC GATGCACTTGATGATTTTGACTTGGATATGCTCGGAAGCCGGGCCAAACGATCTGGCTCTGGCCAGTG TACCAACTATGCCCTGCTCAAGCTCGCTGGCGACGTCGAGTCTAACCCTGGACCAATGGGAGCTGGCG CTACAGGCAGAGCTATGGATGGACCTAGACTGCTGCTGCTCCTGCTTCTGGGAGTGTCTCTTGGCGGA GCCAAAGAGGCCTGTCCTACCGGCCTGTATACACACTCTGGCGAGTGCTGCAAGGCCTGCAATCTTGG AGAAGGCGTCGCACAGCCTTGCGGCGCTAATCAGACAGTGTGCGAGCCTTGCCTGGACAGCGTGACCT TTAGCGACGTGGTGTCAGCCACCGAGCCATGCAAGCCATGTACCGAGTGTGTGGGCCTGCAGAGCATG TCTGCCCCTTGCGTGGAAGCTGACGATGCCGTGTGTAGATGCGCCTACGGCTACTACCAGGACGAGAC AACAGGCAGATGCGAGGCCTGTAGAGTGTGCGAAGCTGGATCTGGCCTGGTGTTCAGCTGCCAAGACA AGCAGAACACCGTGTGCGAGGAATGCCCCGATGGCACCTATAGCGACGAGGCCAACCATGTGGATCCC TGCCTGCCTTGTACCGTGTGTGAAGATACCGAGCGGCAGCTGCGCGAGTGTACAAGATGGGCTGATGC CGAGTGCGAAGAGATCCCTGGCAGATGGATCACCAGAAGCACACCTCCAGAGGGCAGCGATAGCACAG CCCCTTCTACACAAGAGCCCGAGGCTCCTCCTGAGCAGGACCTGATTGCTTCTACAGTGGCTGGCGTC GTGACCACCGTGATGGGATCTAGTCAGCCCGTGGTCACCAGAGGCACCACCGACAATCTGATCCCCGT GTACTGTAGCATCCTGGCCGCCGTGGTTGTTGGACTGGTGGCCTATATCGCCTTCAAGCGGTGGAACA GCTGA(SEQ ID NO: 108)SNIPR-5 DesignCD8a SP - myc tag - BB7.2 - CD45 ECD - human NOTCH1 NRR- NOTCH1 TMD - NOTCH2 JMD - Gal4DBD VP64 TF - E2A - tNGFRAmino Acid Sequence for SNIPR-5 MALPVTALLLPLALLLHAARPEQKLISEEDLQVQLQQSGPELVKPGASVKMSCKASGYTFTSYHIQWV KQRPGQGLEWIGWIYPGDGSTQYNEKFKGKTTLTADKSSSTAYMLLSSLTSEDSAIYFCAREGTYYAM DYWGQGTSVTVSSGGGGSGGGGSGGGGSDIVMTQAPLSLPVSLGDQVSISCRSSQSIVHSNGNTYLEW YLQKPGQSPKLLIYKVSNRFSGVPDRFSGSGSGTDFTLKISRVEAEDLGVYYCFQGSHVPRT FGGGTK LELKRTQSPTPSPTGLTTAKMPSVPLSSDPLPTHTTAFSPASTFERENDFSETTTSLSPDNTSTQVSP DSLDNASAFNTTGVSSVQTPHLPTHADSQTPSAGTDTQTFSGSAANAKLNPTPGSNAISDVPGERSTA STFPTDPVSPLTTTLSLAHHSSAALPARTSNTTITANTSDAYLNASETTTLSPSGSAVISTTTIATTP SKPTCDEKYANITVDYLYNKETKLFT KLNVNENVECGNNTCTNNEVHNLTECKNASVSISHNSCTAP DKTLILDVPPGVEKFQLHDCTQVEKADTTICLKWKNIETFTCDTQNITYRFQCGNMIFDNKEIKLENL EPEHEYKCDSEILYNNHKFTNASKIIKTDFGSPGEPQIIFCRSEAAHQGVITWNPPQRSFHNFTLCYI KETEKDCLNLDKNLIKYDLQNLKPYTKYVLSLHAYIIAKVQRNGSAAMCHFTTKSAPPSQVWNMTVSM TSDNSMHVKCRPPRDRNGPHERYHLEVEAGNTLVRNESHKNCDFRVKDLQYSTDYTFKAYFHNGDYPG EPFILHHSTSYNSKILDYSFGGGAGRDIPPPLIEEACELPECQEDAGNKVCSLQCNNHACGWDGGDCSAttorney Docket No. 44807-0518WO1 / P18835-01LNFNDPWKNCTQSLQCWKYFSDGHCDSQCNSAGCLFDGFDCQRAEGQCNPLYDQYCKDHFSDGHCDQG CNSAECEWDGLDCAEHVPERLAAGTLVVVVLMPPEQLRNSSFHFLRELSRVLHTNVVFKRDAHGQQMI FPYYGREEELRKHPIKRAAEGWAAPDALLGQVKASLLPGGSEGGRRRRELDPMDVRGSIVYLEIDNRQ CVQASSQCFQSATDVAAFLGALASLGSLNIPYKIEAVQSETVEPPPPAQLHFMYVAAAAFVLLFFVGC GVLLSKRKRKHMKLLSSIEQACDICRLKKLKCSKEKPKCAKCLKNNWECRYSPKTKRSPLTRAHLTEV ESRLERLEQLFLLI FPREDLDMILKMDSLQDIKALLTGLFVQDNVNKDAVTDRLASVETDMPLTLRQH RISATSSSEESSNKGQRQLTVSAAAGGSGGSGGSDALDDFDLDMLGSDALDDFDLDMLGSDALDDFDL DMLGSDALDDFDLDMLGSRAKRSGSGQCTNYALLKLAGDVESNPGPMGAGATGRAMDGPRLLLLLLLG VSLGGAKEACPTGLYTHSGECCKACNLGEGVAQPCGANQTVCEPCLDSVTFSDVVSATEPCKPCTECV GLQSMSAPCVEADDAVCRCAYGYYQDETTGRCEACRVCEAGSGLVFSCQDKQNTVCEECPDGTYSDEA NHVDPCLPCTVCEDTERQLRECTRWADAECEEIPGRWITRSTPPEGSDSTAPSTQEPEAPPEQDLI S TVAGVVTTVMGSSQPVVTRGTTDNLIPVYCSILAAVVVGLVAYIAFKRWNS*(SEQ ID NO: 109)Nucleic Acid Sequence for SNIPR-5 ATGGCTCTGCCTGTGACAGCTCTGCTGCTGCCTCTGGCTCTGCTTCTGCATGCCGCTAGACCTGAGCA GAAGCTGATCTCCGAAGAGGACCTGCAGGTTCAGCTGCAGCAGTCTGGACCTGAGCTGGTTAAGCCTG GCGCTTCCGTGAAGATGAGCTGCAAGGCCAGCGGCTACACCTTCACCAGCTACCACATCCAGTGGGTC AAGCAGAGGCCTGGACAGGGACTCGAGTGGATCGGCTGGATCTATCCTGGCGACGGCAGCACCCAGTA CAACGAGAAGTTCAAGGGCAAGACCACACTGACCGCCGACAAGAGCAGCAGCACAGCCTACATGCTGC TGAGCAGCCTGACCAGCGAGGACAGCGCCATCTACTTTTGTGCCAGAGAGGGCACCTACTACGCCATG GATTATTGGGGCCAGGGCACCAGCGTGACAGTCTCTTCTGGTGGCGGAGGATCTGGCGGAGGTGGAAG CGGCGGAGGCGGATCTGATATCGTGATGACACAGGCCCCTCTGAGCCTGCCTGTGTCTCTGGGAGATC AGGTGTCCATCAGCTGTCGGAGCAGCCAGAGCATCGTGCACAGCAACGGCAACACCTACCTGGAATGG TATCTGCAGAAGCCCGGACAGAGCCCCAAGCTGCTGATCTACAAGGTGTCCAACCGGTTCAGCGGCGT GCCCGATAGATTTTCTGGCTCTGGCAGCGGCACCGACTTCACCCTGAAGATCTCTAGAGTGGAAGCCG AGGACCTGGGCGTGTACTACTGCTTCCAAGGCAGCCACGTGCCAAGAACCTTTGGCGGCGGAACAAAG CTGGAACTGAAGCGGACACAGAGCCCCACACCATCTCCAACAGGACTGACCACCGCCAAGATGCCTAG CGTGCCCCTCTCTTCTGACCCTCTGCCTACACACACCACCGCTTTTAGCCCTGCCAGCACCTTCGAGA GAGAGAACGACTTCAGCGAGACAACCACCTCTCTGAGCCCCGACAACACCAGCACACAGGTGTCCCCA GACAGCCTGGATAATGCCAGCGCCTTCAATACCACCGGCGTGTCCTCTGTGCAGACCCCTCATCTGCC AACACACGCCGATAGCCAGACACCTTCTGCCGGCACCGATACACAGACCTTTTCTGGCTCTGCCGCCA ACGCCAAGCTGAACCCTACACCTGGCAGCAACGCCATCTCTGATGTGCCTGGCGAGAGAAGCACCGCC AGCACATTTCCAACAGACCCCGTGTCTCCCCTGACCACCACACTGTCTCTGGCCCACCATAGCTCTGC TGCCCTGCCTGCCAGAACCAGCAACACCACCATCACCGCCAATACCAGCGACGCCTACCTGAACGCCA GCGAAACCACAACACTGAGCCCTAGCGGAAGCGCCGTGATCAGCACAACCACAATCGCCACCACACCT AGCAAGCCTACCTGCGACGAGAAGTACGCCAACATCACCGTGGACTACCTGTACAACAAAGAGACAAA GCTGTTCACGGCCAAGCTCAACGTGAACGAGAACGTGGAATGCGGCAACAATACCTGCACCAACAACG AGGTGCACAACCTGACCGAGTGCAAGAACGCCTCCGTGTCCATCAGCCACAACAGCTGCACAGCCCCT GACAAGACCCTGATCCTGGATGTGCCTCCTGGCGTGGAAAAGTTCCAGCTGCACGATTGCACCCAGGT GGAAAAGGCCGATACCACCATCTGCCTGAAGTGGAAGAACATCGAGACATTCACCTGTGACACCCAGA ACATCACCTACCGGTTCCAGTGCGGCAATATGATCTTCGATAACAAAGAAATCAAGCTCGAGAACCTC GAGCCTGAGCACGAGTACAAGTGCGACAGCGAGATCCTGTATAACAATCACAAGTTCACCAACGCCAG CAAGATCATCAAGACCGACTTCGGCTCTCCCGGCGAGCCCCAGATCATCTTCTGTAGATCTGAGGCCG CTCACCAGGGCGTGATCACCTGGAATCCTCCACAGCGGAGCTTCCACAACTTCACCCTGTGCTACATC AAAGAAACCGAGAAGGACTGCCTGAACCTGGACAAGAACCTCATTAAGTACGACCTGCAGAACCTGAA GCCGTACACCAAATACGTGCTGAGCCTGCACGCCTACATCATTGCCAAGGTGCAGAGAAATGGCAGCG CCGCCATGTGCCACTTCACCACAAAAAGCGCCCCTCCAAGCCAAGTGTGGAACATGACCGTGTCTATGAttorney Docket No. 44807-0518WO1 / P18835-01ACCAGCGACAACTCCATGCACGTGAAGTGCCGGCCTCCACGGGATAGAAATGGCCCTCACGAGAGATA CCACCTGGAAGTCGAGGCCGGAAATACCCTCGTGCGGAACGAGAGCCACAAGAACTGCGACTTCAGAG TGAAGGACCTGCAGTACAGCACCGACTACACCTTCAAGGCCTACTTCCACAATGGCGACTACCCTGGC GAGCCCTTCATCCTGCACCACAGCACCAGCTACAACAGCAAGATCCTGGACTACAGCTTCGGCGGAGG CGCCGGAAGAGATATTCCTCCACCTCTGATCGAGGAAGCCTGCGAGCTGCCTGAGTGTCAAGAGGACG CCGGCAACAAAGTGTGCAGCCTGCAGTGCAACAATCACGCCTGTGGATGGGATGGCGGCGACTGCAGC CTGAACTTCAACGACCCCTGGAAGAACTGCACCCAGTCTCTGCAGTGCTGGAAGTACTTTAGCGACGG CCACTGCGACAGCCAGTGTAATTCTGCCGGCTGCCTGTTCGACGGCTTCGATTGTCAGCGAGCCGAGG GCCAATGCAACCCTCTGTACGACCAGTACTGCAAGGACCACTTCTCCGATGGCCACTGTGACCAGGGC TGTAATAGCGCCGAGTGCGAGTGGGATGGACTGGATTGTGCCGAGCACGTGCCAGAAAGACTGGCCGC TGGAACACTGGTGGTGGTCGTTCTGATGCCTCCTGAGCAGCTGCGGAACAGCAGCTTCCACTTCCTGC GGGAACTGAGCAGAGTGCTGCACACCAACGTGGTGTTCAAGAGAGATGCCCACGGCCAGCAGATGATC TTCCCATATTACGGCAGAGAAGAGGAACTGCGGAAGCACCCCATTAAGAGAGCCGCTGAAGGCTGGGC TGCTCCCGATGCACTTCTGGGACAAGTGAAGGCCTCTCTGCTGCCTGGTGGATCTGAAGGCGGCAGAC GTAGAAGAGAACTGGACCCCATGGATGTGCGGGGCAGCATCGTGTACCTGGAAATCGACAACCGGCAG TGCGTGCAGGCCAGCTCTCAGTGTTTTCAGAGCGCTACAGACGTGGCCGCCTTTCTGGGAGCACTGGC TTCTCTGGGCTCCCTGAACATCCCCTACAAGATCGAGGCCGTGCAGAGCGAGACAGTGGAACCTCCTC CTCCTGCTCAACTGCACTTTATGTACGTGGCCGCTGCTGCCTTCGTGCTGCTGTTCTTTGTTGGCTGC GGAGTGCTGCTGAGCAAGCGGAAGAGAAAGCACATGAAGCTGCTGAGCAGCATCGAGCAGGCCTGTGA CATCTGCCGGCTGAAGAAACTGAAGTGCAGCAAAGAAAAGCCCAAGTGCGCCAAGTGCCTGAAGAACA ACTGGGAGTGCCGGTACAGCCCCAAGACCAAGAGAAGCCCTCTGACAAGAGCCCACCTGACCGAGGTG GAAAGCCGGCTGGAAAGACTCGAGCAGCTGTTCCTGCTGATCTTCCCCAGAGAAGATCTGGACATGAT CCTGAAGATGGACAGCCTGCAGGACATCAAGGCCCTGCTGACCGGACTGTTCGTGCAGGACAACGTGA ACAAGGACGCCGTGACCGATAGACTGGCCAGCGTGGAAACCGACATGCCCCTGACACTGCGGCAGCAC AGAATCAGCGCCACAAGCAGCAGCGAGGAAAGCAGCAACAAGGGCCAGAGACAGCTGACAGTGTCTGC TGCTGCTGGCGGAAGCGGAGGATCTGGTGGATCTGATGCCCTGGACGACTTCGACCTGGATATGCTGG GCAGCGACGCCCTGGATGATTTCGATCTCGACATGCTCGGCTCCGACGCTCTCGACGACTTTGATTTG GACATGTTGGGCTCCGATGCACTTGATGATTTTGACTTGGATATGCTCGGAAGCCGGGCCAAACGATC TGGCTCTGGCCAGTGTACCAACTATGCCCTGCTCAAGCTCGCTGGCGACGTCGAGTCTAACCCTGGAC CAATGGGAGCTGGCGCTACAGGCAGAGCTATGGATGGACCTAGACTGCTGCTGCTCCTGCTTCTGGGA GTGTCTCTTGGCGGAGCCAAAGAGGCCTGTCCTACCGGCCTGTATACACACTCTGGCGAGTGCTGCAA GGCCTGCAATCTTGGAGAAGGCGTCGCACAGCCTTGCGGCGCTAATCAGACAGTGTGCGAGCCTTGCC TGGACAGCGTGACCTTTAGCGACGTGGTGTCAGCCACCGAGCCATGCAAGCCATGTACCGAGTGTGTG GGCCTGCAGAGCATGTCTGCCCCTTGCGTGGAAGCTGACGATGCCGTGTGTAGATGCGCCTACGGCTA CTACCAGGACGAGACAACAGGCAGATGCGAGGCCTGTAGAGTGTGCGAAGCTGGATCTGGCCTGGTGT TCAGCTGCCAAGACAAGCAGAACACCGTGTGCGAGGAATGCCCCGATGGCACCTATAGCGACGAGGCC AACCATGTGGATCCCTGCCTGCCTTGTACCGTGTGTGAAGATACCGAGCGGCAGCTGCGCGAGTGTAC AAGATGGGCTGATGCCGAGTGCGAAGAGATCCCTGGCAGATGGATCACCAGAAGCACACCTCCAGAGG GCAGCGATAGCACAGCCCCTTCTACACAAGAGCCCGAGGCTCCTCCTGAGCAGGACCTGATTGCTTCT ACAGTGGCTGGCGTCGTGACCACCGTGATGGGATCTAGTCAGCCCGTGGTCACCAGAGGCACCACCGA CAATCTGATCCCCGTGTACTGTAGCATCCTGGCCGCCGTGGTTGTTGGACTGGTGGCCTATATCGCCT TCAAGCGGTGGAACAGCTGA(SEQ ID NO: 110)SNIPR-5 RAM7 DesignCD8a SP - myc tag - BB7.2 - CD45 ECD - human NOTCH1 NRR- NOTCH1 TMD - NOTCH2 JMD - RAM7 - Gal4DBD_VP64 TF - E2A - tNGFRAttorney Docket No. 44807-0518WO1 / P18835-01Amino Acid Sequence for SNIPR-5 RAM7 MALPVTALLLPLALLLHAARPEQKLISEEDLQVQLQQSGPELVKPGASVKMSCKASGYTFTSYHIQWV KQRPGQGLEWIGWIYPGDGSTQYNEKFKGKTTLTADKSSSTAYMLLSSLTSEDSAIYFCAREGTYYAM DYWGQGTSVTVSSGGGGSGGGGSGGGGSDIVMTQAPLSLPVSLGDQVSISCRSSQSIVHSNGNTYLEW YLQKPGQSPKLLIYKVSNRFSGVPDRFSGSGSGTDFTLKISRVEAEDLGVYYCFQGSHVPRTFGGGTK LELKRTQSPTPSPTGLTTAKMPSVPLSSDPLPTHTTAFSPASTFERENDFSETTTSLSPDNTSTQVSP DSLDNASAFNTTGVSSVQTPHLPTHADSQTPSAGTDTQTFSGSAANAKLNPTPGSNAISDVPGERSTA STFPTDPVSPLTTTLSLAHHSSAALPARTSNTTITANTSDAYLNASETTTLSPSGSAVISTTTIATTP SKPTCDEKYANITVDYLYNKETKLFTAKLNVNENVECGNNTCTNNEVHNLTECKNASVSISHNSCTAP DKTLILDVPPGVEKFQLHDCTQVEKADTTICLKWKNIETFTCDTQNITYRFQCGNMIFDNKEIKLENL EPEHEYKCDSEILYNNHKFTNASKIIKTDFGSPGEPQIIFCRSEAAHQGVITWNPPQRSFHNFTLCYI KETEKDCLNLDKNLIKYDLQNLKPYTKYVLSLHAYIIAKVQRNGSAAMCHFTTKSAPPSQVWNMTVSM TSDNSMHVKCRPPRDRNGPHERYHLEVEAGNTLVRNESHKNCDFRVKDLQYSTDYTFKAYFHNGDYPG EPFILHHSTSYNSKILDYSFGGGAGRDIPPPLIEEACELPECQEDAGNKVCSLQCNNHACGWDGGDCS LNFNDPWKNCTQSLQCWKYFSDGHCDSQCNSAGCLFDGFDCQRAEGQCNPLYDQYCKDHFSDGHCDQG CNSAECEWDGLDCAEHVPERLAAGTLVVVVLMPPEQLRNSSFHFLRELSRVLHTNVVFKRDAHGQQMI FPYYGREEELRKHPIKRAAEGWAAPDALLGQVKASLLPGGSEGGRRRRELDPMDVRGSIVYLEIDNRQ CVQASSQCFQSATDVAAFLGALASLGSLNIPYKIEAVQSETVEPPPPAQLHFMYVAAAAFVLLFFVGC GVLLSKRKRKHQHGQLWFMKLLSSIEQACDICRLKKLKCSKEKPKCAKCLKNNWECRYSPKTKRSPLT RAHLTEVESRLERLEQLFLLIFPREDLDMILKMDSLQDIKALLTGLFVQDNVNKDAVTDRLASVETDM PLTLRQHRISATSSSEESSNKGQRQLTVSAAAGGSGGSGGSDALDDFDLDMLGSDALDDFDLDMLGSD ALDDFDLDMLGSDALDDFDLDMLGSRAKRSGSGQCTNYALLKLAGDVESNPGPMGAGATGRAMDGPRL LLLLLLGVSLGGAKEACPTGLYTHSGECCKACNLGEGVAQPCGANQTVCEPCLDSVTFSDVVSATEPC KPCTECVGLQSMSAPCVEADDAVCRCAYGYYQDETTGRCEACRVCEAGSGLVFSCQDKQNTVCEECPD GTYSDEANHVDPCLPCTVCEDTERQLRECTRWADAECEEIPGRWITRSTPPEGSDSTAPSTQEPEAPP EQDLIASTVAGVVTTVMGSSQPVVTRGTTDNLIPVYCSILAAVVVGLVAYIAFKRWNS*(SEQ ID NO: 111)Nucleic Acid Sequence for SNIPR-5 RAM7 ATGGCTCTGCCTGTGACAGCTCTGCTGCTGCCTCTGGCTCTGCTTCTGCATGCCGCTAGACCTGAGCA GAAGCTGATCTCCGAAGAGGACCTGCAGGTTCAGCTGCAGCAGTCTGGACCTGAGCTGGTTAAGCCTG GCGCTTCCGTGAAGATGAGCTGCAAGGCCAGCGGCTACACCTTCACCAGCTACCACATCCAGTGGGTC AAGCAGAGGCCTGGACAGGGACTCGAGTGGATCGGCTGGATCTATCCTGGCGACGGCAGCACCCAGTA CAACGAGAAGTTCAAGGGCAAGACCACACTGACCGCCGACAAGAGCAGCAGCACAGCCTACATGCTGC TGAGCAGCCTGACCAGCGAGGACAGCGCCATCTACTTTTGTGCCAGAGAGGGCACCTACTACGCCATG GATTATTGGGGCCAGGGCACCAGCGTGACAGTCTCTTCTGGTGGCGGAGGATCTGGCGGAGGTGGAAG CGGCGGAGGCGGATCTGATATCGTGATGACACAGGCCCCTCTGAGCCTGCCTGTGTCTCTGGGAGATC AGGTGTCCATCAGCTGTCGGAGCAGCCAGAGCATCGTGCACAGCAACGGCAACACCTACCTGGAATGG TATCTGCAGAAGCCCGGACAGAGCCCCAAGCTGCTGATCTACAAGGTGTCCAACCGGTTCAGCGGCGT GCCCGATAGATTTTCTGGCTCTGGCAGCGGCACCGACTTCACCCTGAAGATCTCTAGAGTGGAAGCCG AGGACCTGGGCGTGTACTACTGCTTCCAAGGCAGCCACGTGCCAAGAACCTTTGGCGGCGGAACAAAG CTGGAACTGAAGCGGACACAGAGCCCCACACCATCTCCAACAGGACTGACCACCGCCAAGATGCCTAG CGTGCCCCTCTCTTCTGACCCTCTGCCTACACACACCACCGCTTTTAGCCCTGCCAGCACCTTCGAGA GAGAGAACGACTTCAGCGAGACAACCACCTCTCTGAGCCCCGACAACACCAGCACACAGGTGTCCCCA GACAGCCTGGATAATGCCAGCGCCTTCAATACCACCGGCGTGTCCTCTGTGCAGACCCCTCATCTGCC AACACACGCCGATAGCCAGACACCTTCTGCCGGCACCGATACACAGACCTTTTCTGGCTCTGCCGCCA ACGCCAAGCTGAACCCTACACCTGGCAGCAACGCCATCTCTGATGTGCCTGGCGAGAGAAGCACCGCCAttorney Docket No. 44807-0518WO1 / P18835-01AGCACATTTCCAACAGACCCCGTGTCTCCCCTGACCACCACACTGTCTCTGGCCCACCATAGCTCTGC TGCCCTGCCTGCCAGAACCAGCAACACCACCATCACCGCCAATACCAGCGACGCCTACCTGAACGCCA GCGAAACCACAACACTGAGCCCTAGCGGAAGCGCCGTGATCAGCACAACCACAATCGCCACCACACCT AGCAAGCCTACCTGCGACGAGAAGTACGCCAACATCACCGTGGACTACCTGTACAACAAAGAGACAAA GCTGTTCACGGCCAAGCTCAACGTGAACGAGAACGTGGAATGCGGCAACAATACCTGCACCAACAACG AGGTGCACAACCTGACCGAGTGCAAGAACGCCTCCGTGTCCATCAGCCACAACAGCTGCACAGCCCCT GACAAGACCCTGATCCTGGATGTGCCTCCTGGCGTGGAAAAGTTCCAGCTGCACGATTGCACCCAGGT GGAAAAGGCCGATACCACCATCTGCCTGAAGTGGAAGAACATCGAGACATTCACCTGTGACACCCAGA ACATCACCTACCGGTTCCAGTGCGGCAATATGATCTTCGATAACAAAGAAATCAAGCTCGAGAACCTC GAGCCTGAGCACGAGTACAAGTGCGACAGCGAGATCCTGTATAACAATCACAAGTTCACCAACGCCAG CAAGATCATCAAGACCGACTTCGGCTCTCCCGGCGAGCCCCAGATCATCTTCTGTAGATCTGAGGCCG CTCACCAGGGCGTGATCACCTGGAATCCTCCACAGCGGAGCTTCCACAACTTCACCCTGTGCTACATC AAAGAAACCGAGAAGGACTGCCTGAACCTGGACAAGAACCTCATTAAGTACGACCTGCAGAACCTGAA GCCGTACACCAAATACGTGCTGAGCCTGCACGCCTACATCATTGCCAAGGTGCAGAGAAATGGCAGCG CCGCCATGTGCCACTTCACCACAAAAAGCGCCCCTCCAAGCCAAGTGTGGAACATGACCGTGTCTATG ACCAGCGACAACTCCATGCACGTGAAGTGCCGGCCTCCACGGGATAGAAATGGCCCTCACGAGAGATA CCACCTGGAAGTCGAGGCCGGAAATACCCTCGTGCGGAACGAGAGCCACAAGAACTGCGACTTCAGAG TGAAGGACCTGCAGTACAGCACCGACTACACCTTCAAGGCCTACTTCCACAATGGCGACTACCCTGGC GAGCCCTTCATCCTGCACCACAGCACCAGCTACAACAGCAAGATCCTGGACTACAGCTTCGGCGGAGG CGCCGGAAGAGATATTCCTCCACCTCTGATCGAGGAAGCCTGCGAGCTGCCTGAGTGTCAAGAGGACG CCGGCAACAAAGTGTGCAGCCTGCAGTGCAACAATCACGCCTGTGGATGGGATGGCGGCGACTGCAGC CTGAACTTCAACGACCCCTGGAAGAACTGCACCCAGTCTCTGCAGTGCTGGAAGTACTTTAGCGACGG CCACTGCGACAGCCAGTGTAATTCTGCCGGCTGCCTGTTCGACGGCTTCGATTGTCAGCGAGCCGAGG GCCAATGCAACCCTCTGTACGACCAGTACTGCAAGGACCACTTCTCCGATGGCCACTGTGACCAGGGC TGTAATAGCGCCGAGTGCGAGTGGGATGGACTGGATTGTGCCGAGCACGTGCCAGAAAGACTGGCCGC TGGAACACTGGTGGTGGTCGTTCTGATGCCTCCTGAGCAGCTGCGGAACAGCAGCTTCCACTTCCTGC GGGAACTGAGCAGAGTGCTGCACACCAACGTGGTGTTCAAGAGAGATGCCCACGGCCAGCAGATGATC TTCCCATATTACGGCAGAGAAGAGGAACTGCGGAAGCACCCCATTAAGAGAGCCGCTGAAGGCTGGGC TGCTCCCGATGCACTTCTGGGACAAGTGAAGGCCTCTCTGCTGCCTGGTGGATCTGAAGGCGGCAGAC GTAGAAGAGAACTGGACCCCATGGATGTGCGGGGCAGCATCGTGTACCTGGAAATCGACAACCGGCAG TGCGTGCAGGCCAGCTCTCAGTGTTTTCAGAGCGCTACAGACGTGGCCGCCTTTCTGGGAGCACTGGC TTCTCTGGGCTCCCTGAACATCCCCTACAAGATCGAGGCCGTGCAGAGCGAGACAGTGGAACCTCCTC CTCCTGCTCAACTGCACTTTATGTACGTGGCCGCTGCTGCCTTCGTGCTGCTGTTCTTTGTTGGCTGC GGAGTGCTGCTGAGCAAGCGGAAGAGAAAGCACCAGCATGGCCAGCTGTGGTTCATGAAGCTGCTGAG CAGCATCGAGCAGGCCTGTGACATCTGCCGGCTGAAGAAACTGAAGTGCAGCAAAGAAAAGCCCAAGT GCGCCAAGTGCCTGAAGAACAACTGGGAGTGCCGGTACAGCCCCAAGACCAAGAGAAGCCCTCTGACA AGAGCCCACCTGACCGAGGTGGAAAGCCGGCTGGAAAGACTCGAGCAGCTGTTCCTGCTGATCTTCCC CAGAGAAGATCTGGACATGATCCTGAAGATGGACAGCCTGCAGGACATCAAGGCCCTGCTGACCGGAC TGTTCGTGCAGGACAACGTGAACAAGGACGCCGTGACCGATAGACTGGCCAGCGTGGAAACCGACATG CCCCTGACACTGCGGCAGCACAGAATCAGCGCCACAAGCAGCAGCGAGGAAAGCAGCAACAAGGGCCA GAGACAGCTGACAGTGTCTGCTGCTGCTGGCGGAAGCGGAGGATCTGGTGGATCTGATGCCCTGGACG ACTTCGACCTGGATATGCTGGGCAGCGACGCCCTGGATGATTTCGATCTCGACATGCTCGGCTCCGAC GCTCTCGACGACTTTGATTTGGACATGTTGGGCTCCGATGCACTTGATGATTTTGACTTGGATATGCT CGGAAGCCGGGCCAAACGATCTGGCTCTGGCCAGTGTACCAACTATGCCCTGCTCAAGCTCGCTGGCG ACGTCGAGTCTAACCCTGGACCAATGGGAGCTGGCGCTACAGGCAGAGCTATGGATGGACCTAGACTG CTGCTGCTCCTGCTTCTGGGAGTGTCTCTTGGCGGAGCCAAAGAGGCCTGTCCTACCGGCCTGTATAC ACACTCTGGCGAGTGCTGCAAGGCCTGCAATCTTGGAGAAGGCGTCGCACAGCCTTGCGGCGCTAATC AGACAGTGTGCGAGCCTTGCCTGGACAGCGTGACCTTTAGCGACGTGGTGTCAGCCACCGAGCCATGC AAGCCATGTACCGAGTGTGTGGGCCTGCAGAGCATGTCTGCCCCTTGCGTGGAAGCTGACGATGCCGTAttorney Docket No. 44807-0518WO1 / P18835-01GTGTAGATGCGCCTACGGCTACTACCAGGACGAGACAACAGGCAGATGCGAGGCCTGTAGAGTGTGCG AAGCTGGATCTGGCCTGGTGTTCAGCTGCCAAGACAAGCAGAACACCGTGTGCGAGGAATGCCCCGAT GGCACCTATAGCGACGAGGCCAACCATGTGGATCCCTGCCTGCCTTGTACCGTGTGTGAAGATACCGA GCGGCAGCTGCGCGAGTGTACAAGATGGGCTGATGCCGAGTGCGAAGAGATCCCTGGCAGATGGATCA CCAGAAGCACACCTCCAGAGGGCAGCGATAGCACAGCCCCTTCTACACAAGAGCCCGAGGCTCCTCCT GAGCAGGACCTGATTGCTTCTACAGTGGCTGGCGTCGTGACCACCGTGATGGGATCTAGTCAGCCCGT GGTCACCAGAGGCACCACCGACAATCTGATCCCCGTGTACTGTAGCATCCTGGCCGCCGTGGTTGTTG GACTGGTGGCCTATATCGCCTTCAAGCGGTGGAACAGCTGA(SEQ ID NO: 112)Example 4: Exemplary CAR SequencesThis Example provides sequences of exemplary CAR molecules.45ECD-CAR-1 DesignCD8a SP - myc tag - CD45 ECD - CD45 TMD - CD45 JMD - 4 IBB CoStim - Linker 1 - RR Leucine Zipper - Linker 2 - P2A - GMCSFRa SP - FLAG tag - FMC63 - CD8a Hinge - CD8a TMD - 4 IBB CoStim - Linker 3 - EE Leucine Zipper - Linker 2 - CD3z Signaling - E2A - tNGFRAmino Acid Sequence for 45ECD-CAR-1 MALPVTALLLPLALLLHAARPEQKLISEEDLQSPTPSPTGLTTAKMPSVPLSSDPLPTHTTAFSPAST FERENDFSETTTSLSPDNTSTQVSPDSLDNASAFNTTGVSSVQTPHLPTHADSQTPSAGTDTQTFSGS AANAKLNPTPGSNAISDVPGERSTASTFPTDPVSPLTTTLSLAHHSSAALPARTSNTTITANTSDAYL NASETTTLSPSGSAVISTTTIATTPSKPTCDEKYANITVDYLYNKETKLFTAKLNVNENVECGNNTCT NNEVHNLTECKNASVSISHNSCTAPDKTLILDVPPGVEKFQLHDCTQVEKADTTICLKWKNIETFTCD TQNITYRFQCGNMIFDNKEIKLENLEPEHEYKCDSEILYNNHKFTNASKIIKTDFGSPGEPQIIFCRS EAAHQGVITWNPPQRSFHNFTLCYIKETEKDCLNLDKNLIKYDLQNLKPYTKYVLSLHAYIIAKVQRN GSAAMCHFTTKSAPPSQVWNMTVSMTSDNSMHVKCRPPRDRNGPHERYHLEVEAGNTLVRNESHKNCD FRVKDLQYSTDYTFKAYFHNGDYPGEPFILHHSTSYNSKALIAFLAFLIIVTSI LLVVLYKIYDLHK KRKRGRKKLLYI FKQPFMRPVQTTQEEDGCSCRFPEEEEGGCELSRGSGSGSGSMDPDLEIRAAFLRQ RNTALRTEVAELEQEVQRLENEVSQYETRYGPLGGGKGSGSGSGSSLRAKRSGSGATNFSLLKQAGDV EENPGPMLLLVTSLLLCELPHPAFLLIPDYKDDDDKDIQMTQTTSSLSASLGDRVTISCRASQDISKY LNWYQQKPDGTVKLLIYHTSRLHSGVPSRFSGSGSGTDYSLTISNLEQEDIATYFCQQGNTLPYTFGG GTKLEITGSTSGSGKPGSGEGSTKGEVKLQESGPGLVAPSQSLSVTCTVSGVSLPDYGVSWIRQPPRK GLEWLGVIWGSETTYYNSALKSRLTI IKDNSKSQVFLKMNSLQTDDTAIYYCAKHYYYGGSYAMDYWG QGTSVTVSSAAATTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIYIWAPLAG TCGVLLLSLVITKRGRKKLLYI FKQPFMRPVQTTQEEDGCSCRFPEEEEGGCELGSGSGSGSGSGSGS GSMDPDLEIEAAFLERENTALETRVAELRQRVQRLRNRVSQYRTRYGPLGGGKGSGSGSGSSLRVKFS RSADAPAYQQGQNQLYNELNLGRREEYDVLDKRRGRDPEMGGKPQRRKNPQEGLYNELQKDKMAEAYS EIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPRRAKRSGSGQCTNYALLKLAGDVESNPGP MGAGATGRAMDGPRLLLLLLLGVSLGGAKEACPTGLYTHSGECCKACNLGEGVAQPCGANQTVCEPCL DSVTFSDVVSATEPCKPCTECVGLQSMSAPCVEADDAVCRCAYGYYQDETTGRCEACRVCEAGSGLVF SCQDKQNTVCEECPDGTYSDEANHVDPCLPCTVCEDTERQLRECTRWADAECEEIPGRWITRSTPPEG SDSTAPSTQEPEAPPEQDLIASTVAGVVTTVMGSSQPVVTRGTTDNLIPVYCSILAAVVVGLVAYIAF KRWNS*(SEQ ID NO:20)Attorney Docket No. 44807-0518WO1 / P18835-01Nucleic Acid Sequence for 45ECD-CAR-1 ATGGCTCTGCCTGTGACAGCTCTGCTGCTGCCTCTGGCTCTGCTTCTGCATGCCGCTAGACCTGAGCA GAAGCTGATCTCCGAAGAGGACCTGCAGAGCCCCACACCATCTCCAACAGGACTGACCACCGCCAAGA TGCCTAGCGTGCCCCTCTCTTCTGACCCTCTGCCTACACACACCACCGCTTTTAGCCCTGCCAGCACC TTCGAGAGAGAGAACGACTTCAGCGAGACAACCACCTCTCTGAGCCCCGACAACACCAGCACACAGGT GTCCCCAGACAGCCTGGATAATGCCAGCGCCTTCAATACCACCGGCGTGTCCTCTGTGCAGACCCCTC ATCTGCCAACACACGCCGATAGCCAGACACCTTCTGCCGGCACCGATACACAGACCTTTTCTGGCTCT GCCGCCAACGCCAAGCTGAACCCTACACCTGGCAGCAACGCCATCTCTGATGTGCCTGGCGAGAGAAG CACCGCCAGCACATTTCCAACAGACCCCGTGTCTCCCCTGACCACCACACTGTCTCTGGCCCACCATA GCTCTGCTGCCCTGCCTGCCAGAACCAGCAACACCACCATCACCGCCAATACCAGCGACGCCTACCTG AACGCCAGCGAAACCACAACACTGAGCCCTAGCGGAAGCGCCGTGATCAGCACAACCACAATCGCCAC CACACCTAGCAAGCCTACCTGCGACGAGAAGTACGCCAACATCACCGTGGACTACCTGTACAACAAAG AGACAAAGCTGTTCACGGCCAAGCTCAACGTGAACGAGAACGTGGAATGCGGCAACAATACCTGCACC AACAACGAGGTGCACAACCTGACCGAGTGCAAGAACGCCTCCGTGTCCATCAGCCACAACAGCTGCAC AGCCCCTGACAAGACCCTGATCCTGGATGTGCCTCCTGGCGTGGAAAAGTTCCAGCTGCACGATTGCA CCCAGGTGGAAAAGGCCGATACCACCATCTGCCTGAAGTGGAAGAACATCGAGACATTCACCTGTGAC ACCCAGAACATCACCTACCGGTTCCAGTGCGGCAATATGATCTTCGATAACAAAGAAATCAAGCTCGA GAACCTCGAGCCTGAGCACGAGTACAAGTGCGACAGCGAGATCCTGTATAACAATCACAAGTTCACCA ACGCCAGCAAGATCATCAAGACCGACTTCGGCTCTCCCGGCGAGCCCCAGATCATCTTCTGTAGATCT GAGGCCGCTCACCAGGGCGTGATCACCTGGAATCCTCCACAGCGGAGCTTCCACAACTTCACCCTGTG CTACATCAAAGAAACCGAGAAGGACTGCCTGAACCTGGACAAGAACCTCATTAAGTACGACCTGCAGA ACCTGAAGCCGTACACCAAATACGTGCTGAGCCTGCACGCCTACATCATTGCCAAGGTGCAGAGAAAT GGCAGCGCCGCCATGTGCCACTTCACCACAAAAAGCGCCCCTCCAAGCCAAGTGTGGAACATGACCGT GTCTATGACCAGCGACAACTCCATGCACGTGAAGTGCCGGCCTCCACGGGATAGAAATGGCCCTCACG AGAGATACCACCTGGAAGTCGAGGCCGGAAATACCCTCGTGCGGAACGAGAGCCACAAGAACTGCGAC TTCAGAGTGAAGGACCTGCAGTACAGCACCGACTACACCTTCAAGGCCTACTTCCACAATGGCGACTA CCCTGGCGAGCCCTTCATCCTGCACCACAGCACCAGCTACAACAGCAAGGCACTTATCGCGTTCCTCG CGTTTCTCATTATTGTTACATCCATAGCTTTGCTTGTTGTACTTTACAAGATTTATGACCTTCATAAG AAACGAAAGCGGGGCAGAAAGAAGCTGCTGTACATCTTCAAGCAGCCCTTCATGCGGCCCGTGCAGAC CACACAAGAGGAAGATGGCTGCTCCTGCAGATTCCCCGAGGAAGAAGAAGGCGGCTGCGAACTTAGCA GAGGCAGCGGAAGTGGCAGCGGCAGCATGGATCCTGACCTGGAAATCAGAGCCGCCTTTCTGCGGCAG AGAAACACAGCCCTGAGAACCGAAGTGGCCGAGCTGGAACAAGAGGTGCAGCGGCTGGAAAACGAGGT GTCCCAGTACGAGACAAGATACGGCCCTCTCGGCGGAGGCAAAGGCTCTGGTAGTGGCTCTGGAAGCT CTCTGAGGGCCAAGAGAAGTGGAAGCGGCGCCACAAACTTCAGCCTGTTGAAACAGGCCGGGGACGTC GAAGAGAATCCTGGACCAATGCTGCTGCTGGTCACATCTCTGCTGCTGTGCGAGCTGCCCCATCCTGC CTTTCTGCTGATCCCCGACTACAAGGACGACGACGACAAGGACATCCAGATGACCCAGACCACAAGCA GCCTGTCTGCCAGCCTGGGCGATAGAGTGACCATCAGCTGTAGAGCCAGCCAGGACATCAGCAAGTAC CTGAACTGGTATCAGCAAAAGCCCGACGGCACCGTGAAGCTGCTGATCTACCACACCAGCAGACTGCA CAGCGGCGTGCCAAGCAGATTTTCTGGCAGCGGCTCTGGCACCGACTACAGCCTGACAATCAGCAACC TGGAACAAGAGGATATCGCTACCTACTTCTGCCAGCAAGGCAACACCCTGCCTTACACCTTTGGCGGA GGCACCAAGCTGGAAATCACCGGCTCTACAAGCGGCAGCGGCAAACCTGGATCTGGCGAGGGATCTAC CAAGGGCGAAGTGAAACTGCAAGAGTCTGGCCCTGGACTGGTGGCCCCATCTCAGTCTCTGAGCGTGA CCTGTACAGTCAGCGGAGTGTCCCTGCCTGATTACGGCGTGTCCTGGATCAGACAGCCTCCTCGGAAA GGCCTGGAATGGCTGGGAGTGATCTGGGGCAGCGAGACAACCTACTACAACAGCGCCCTGAAGTCCCG GCTGACCATCATCAAGGACAACTCCAAGAGCCAGGTGTTCCTGAAGATGAACAGCCTGCAGACCGACG ACACCGCCATCTACTATTGCGCCAAGCACTACTACTACGGCGGCAGCTACGCCATGGATTATTGGGGC CAGGGCACCAGCGTGACCGTTTCTTCTGCCGCCGCTACAACAACCCCTGCTCCTAGACCTCCTACACC AGCTCCTACAATCGCCAGCCAGCCTCTGTCTCTGAGGCCAGAGGCTTGTAGACCTGCTGCTGGCGGAG CCGTGCATACAAGAGGACTGGATTTCGCCTGCGATATCTACATCTATATCTGGGCTCCTCTGGCCGGCAttorney Docket No. 44807-0518WO1 / P18835-01ACCTGTGGTGTTCTGCTGCTGTCTCTGGTCATCACCAAGCGGGGCAGAAAGAAGCTGCTGTACATCTT CAAGCAGCCCTTCATGCGGCCCGTGCAGACCACACAAGAGGAAGATGGCTGCTCCTGCAGATTCCCCG AGGAAGAAGAAGGCGGCTGCGAACTTGGCAGCGGCTCTGGTAGTGGTTCTGGCTCTGGATCTGGAAGC GGCAGCATGGACCCCGACCTGGAAATTGAAGCCGCCTTTCTGGAAAGAGAGAACACAGCCCTGGAAAC CAGAGTGGCCGAGCTGAGACAGAGAGTGCAGCGGCTGAGAAACCGGGTGTCCCAGTACAGAACCAGAT ACGGACCTCTCGGCGGAGGCAAAGGATCTGGATCAGGCAGCGGAAGCTCTCTGAGAGTGAAGTTCTCC AGATCTGCCGACGCTCCTGCCTATCAGCAGGGCCAGAACCAGCTGTACAACGAGCTGAACCTGGGGAG AAGAGAAGAGTACGACGTGCTGGACAAGCGGAGAGGCAGAGATCCTGAGATGGGCGGAAAGCCCCAGC GGAGAAAGAATCCTCAAGAGGGCCTGTATAATGAGCTGCAGAAAGACAAGATGGCCGAGGCCTACAGC GAGATCGGAATGAAGGGCGAGCGCAGAAGAGGCAAGGGACACGATGGACTGTACCAGGGCCTGTCTAC CGCCACCAAGGATACCTATGACGCCCTGCACATGCAGGCCCTGCCACCTAGACGGGCCAAACGATCTG GCTCTGGCCAGTGTACCAACTATGCCCTGCTCAAGCTCGCTGGCGACGTCGAGTCTAACCCTGGACCA ATGGGAGCTGGCGCTACAGGCAGAGCTATGGATGGACCTAGACTGCTGCTGCTCCTGCTTCTGGGAGT GTCTCTTGGCGGAGCCAAAGAGGCCTGTCCTACCGGCCTGTATACACACTCTGGCGAGTGCTGCAAGG CCTGCAATCTTGGAGAAGGCGTCGCACAGCCTTGCGGCGCTAATCAGACAGTGTGCGAGCCTTGCCTG GACAGCGTGACCTTTAGCGACGTGGTGTCAGCCACCGAGCCATGCAAGCCATGTACCGAGTGTGTGGG CCTGCAGAGCATGTCTGCCCCTTGCGTGGAAGCTGACGATGCCGTGTGTAGATGCGCCTACGGCTACT ACCAGGACGAGACAACAGGCAGATGCGAGGCCTGTAGAGTGTGCGAAGCTGGATCTGGCCTGGTGTTC AGCTGCCAAGACAAGCAGAACACCGTGTGCGAGGAATGCCCCGATGGCACCTATAGCGACGAGGCCAA CCATGTGGATCCCTGCCTGCCTTGTACCGTGTGTGAAGATACCGAGCGGCAGCTGCGCGAGTGTACAA GATGGGCTGATGCCGAGTGCGAAGAGATCCCTGGCAGATGGATCACCAGAAGCACACCTCCAGAGGGC AGCGATAGCACAGCCCCTTCTACACAAGAGCCCGAGGCTCCTCCTGAGCAGGACCTGATTGCTTCTAC AGTGGCTGGCGTCGTGACCACCGTGATGGGATCTAGTCAGCCCGTGGTCACCAGAGGCACCACCGACA ATCTGATCCCCGTGTACTGTAGCATCCTGGCCGCCGTGGTTGTTGGACTGGTGGCCTATATCGCCTTC AAGCGGTGGAACAGCTGA(SEQ ID NO: 113)CAR-1 DesignCD8a SP - myc tag - K - CD45 TMD - CD45 JMD - 4 IBB CoStim - Linker 1 - RR Leucine Zipper -Linker 2 - P2A - GMCSFRa SP - FLAG tag - FMC63 - CD8a Hinge - CD8a TMD - 4 IBB CoStim -Linker 3 - EE Leucine Zipper - Linker 2 - CD3z Signaling - E2A - tNGFRAmino Acid Sequence for CAR-1 MALPVTALLLPLALLLHAARPEQKLISEEDLKALIAFLAFLIIVTSIALLVVLYKIYDLHKKRKRGRK KLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCELSRGSGSGSGSMDPDLEIRAAFLRQRNTALRT EVAELEQEVQRLENEVSQYETRYGPLGGGKGSGSGSGSSLRAKRSGSGATNFSLLKQAGDVEENPGPM LLLVTSLLLCELPHPAFLLIPDYKDDDDKDIQMTQTTSSLSASLGDRVTISCRASQDISKYLNWYQQK PDGTVKLLIYHTSRLHSGVPSRFSGSGSGTDYSLTISNLEQEDIATYFCQQGNTLPYTFGGGTKLEIT GSTSGSGKPGSGEGSTKGEVKLQESGPGLVAPSQSLSVTCTVSGVSLPDYGVSWIRQPPRKGLEWLGV IWGSETTYYNSALKSRLTIIKDNSKSQVFLKMNSLQTDDTAIYYCAKHYYYGGSYAMDYWGQGTSVTV SSAAATTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIYIWAPLAGTCGVLLL SLVITKRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCELGSGSGSGSGSGSGSGSMDPDL EIEAAFLERENTALETRVAELRQRVQRLRNRVSQYRTRYGPLGGGKGSGSGSGSSLRVKFSRSADAPA YQQGQNQLYNELNLGRREEYDVLDKRRGRDPEMGGKPQRRKNPQEGLYNELQKDKMAEAYSEIGMKGE RRRGKGHDGLYQGLSTATKDTYDALHMQALPPRRAKRSGSGQCTNYALLKLAGDVESNPGPMGAGATG RAMDGPRLLLLLLLGVSLGGAKEACPTGLYTHSGECCKACNLGEGVAQPCGANQTVCEPCLDSVTFSD VVSATEPCKPCTECVGLQSMSAPCVEADDAVCRCAYGYYQDETTGRCEACRVCEAGSGLVFSCQDKQNAttorney Docket No. 44807-0518WO1 / P18835-01TVCEECPDGTYSDEANHVDPCLPCTVCEDTERQLRECTRWADAECEEIPGRWITRSTPPEGSDSTAPS TQEPEAPPEQDLIASTVAGVVTTVMGSSQPVVTRGTTDNLIPVYCSILAAVVVGLVAYIAFKRWNS* (SEQ ID NO:21)Nucleic Acid Sequence for CAR-1 ATGGCTCTGCCTGTGACAGCTCTGCTGCTGCCTCTGGCTCTGCTTCTGCATGCCGCTAGACCTGAGCA GAAGCTGATCTCCGAAGAGGACCTGAAGGCACTTATCGCGTTCCTCGCGTTTCTCATTATTGTTACAT CCATAGCTTTGCTTGTTGTACTTTACAAGATTTATGACCTTCATAAGAAACGAAAGCGGGGCAGAAAG AAGCTGCTGTACATCTTCAAGCAGCCCTTCATGCGGCCCGTGCAGACCACACAAGAGGAAGATGGCTG CTCCTGCAGATTCCCCGAGGAAGAAGAAGGCGGCTGCGAACTTAGCAGAGGCAGCGGAAGTGGCAGCG GCAGCATGGATCCTGACCTGGAAATCAGAGCCGCCTTTCTGCGGCAGAGAAACACAGCCCTGAGAACC GAAGTGGCCGAGCTGGAACAAGAGGTGCAGCGGCTGGAAAACGAGGTGTCCCAGTACGAGACAAGATA CGGCCCTCTCGGCGGAGGCAAAGGCTCTGGTAGTGGCTCTGGAAGCTCTCTGAGGGCCAAGAGAAGTG GAAGCGGCGCCACAAACTTCAGCCTGTTGAAACAGGCCGGGGACGTCGAAGAGAATCCTGGACCAATG CTGCTGCTGGTCACATCTCTGCTGCTGTGCGAGCTGCCCCATCCTGCCTTTCTGCTGATCCCCGACTA CAAGGACGACGACGACAAGGACATCCAGATGACCCAGACCACAAGCAGCCTGTCTGCCAGCCTGGGCG ATAGAGTGACCATCAGCTGTAGAGCCAGCCAGGACATCAGCAAGTACCTGAACTGGTATCAGCAAAAG CCCGACGGCACCGTGAAGCTGCTGATCTACCACACCAGCAGACTGCACAGCGGCGTGCCAAGCAGATT TTCTGGCAGCGGCTCTGGCACCGACTACAGCCTGACAATCAGCAACCTGGAACAAGAGGATATCGCTA CCTACTTCTGCCAGCAAGGCAACACCCTGCCTTACACCTTTGGCGGAGGCACCAAGCTGGAAATCACC GGCTCTACAAGCGGCAGCGGCAAACCTGGATCTGGCGAGGGATCTACCAAGGGCGAAGTGAAACTGCA AGAGTCTGGCCCTGGACTGGTGGCCCCATCTCAGTCTCTGAGCGTGACCTGTACAGTCAGCGGAGTGT CCCTGCCTGATTACGGCGTGTCCTGGATCAGACAGCCTCCTCGGAAAGGCCTGGAATGGCTGGGAGTG ATCTGGGGCAGCGAGACAACCTACTACAACAGCGCCCTGAAGTCCCGGCTGACCATCATCAAGGACAA CTCCAAGAGCCAGGTGTTCCTGAAGATGAACAGCCTGCAGACCGACGACACCGCCATCTACTATTGCG CCAAGCACTACTACTACGGCGGCAGCTACGCCATGGATTATTGGGGCCAGGGCACCAGCGTGACCGTT TCTTCTGCCGCCGCTACAACAACCCCTGCTCCTAGACCTCCTACACCAGCTCCTACAATCGCCAGCCA GCCTCTGTCTCTGAGGCCAGAGGCTTGTAGACCTGCTGCTGGCGGAGCCGTGCATACAAGAGGACTGG ATTTCGCCTGCGATATCTACATCTATATCTGGGCTCCTCTGGCCGGCACCTGTGGTGTTCTGCTGCTG TCTCTGGTCATCACCAAGCGGGGCAGAAAGAAGCTGCTGTACATCTTCAAGCAGCCCTTCATGCGGCC CGTGCAGACCACACAAGAGGAAGATGGCTGCTCCTGCAGATTCCCCGAGGAAGAAGAAGGCGGCTGCG AACTTGGCAGCGGCTCTGGTAGTGGTTCTGGCTCTGGATCTGGAAGCGGCAGCATGGACCCCGACCTG GAAATTGAAGCCGCCTTTCTGGAAAGAGAGAACACAGCCCTGGAAACCAGAGTGGCCGAGCTGAGACA GAGAGTGCAGCGGCTGAGAAACCGGGTGTCCCAGTACAGAACCAGATACGGACCTCTCGGCGGAGGCA AAGGATCTGGATCAGGCAGCGGAAGCTCTCTGAGAGTGAAGTTCTCCAGATCTGCCGACGCTCCTGCC TATCAGCAGGGCCAGAACCAGCTGTACAACGAGCTGAACCTGGGGAGAAGAGAAGAGTACGACGTGCT GGACAAGCGGAGAGGCAGAGATCCTGAGATGGGCGGAAAGCCCCAGCGGAGAAAGAATCCTCAAGAGG GCCTGTATAATGAGCTGCAGAAAGACAAGATGGCCGAGGCCTACAGCGAGATCGGAATGAAGGGCGAG CGCAGAAGAGGCAAGGGACACGATGGACTGTACCAGGGCCTGTCTACCGCCACCAAGGATACCTATGA CGCCCTGCACATGCAGGCCCTGCCACCTAGACGGGCCAAACGATCTGGCTCTGGCCAGTGTACCAACT ATGCCCTGCTCAAGCTCGCTGGCGACGTCGAGTCTAACCCTGGACCAATGGGAGCTGGCGCTACAGGC AGAGCTATGGATGGACCTAGACTGCTGCTGCTCCTGCTTCTGGGAGTGTCTCTTGGCGGAGCCAAAGA GGCCTGTCCTACCGGCCTGTATACACACTCTGGCGAGTGCTGCAAGGCCTGCAATCTTGGAGAAGGCG TCGCACAGCCTTGCGGCGCTAATCAGACAGTGTGCGAGCCTTGCCTGGACAGCGTGACCTTTAGCGAC GTGGTGTCAGCCACCGAGCCATGCAAGCCATGTACCGAGTGTGTGGGCCTGCAGAGCATGTCTGCCCC TTGCGTGGAAGCTGACGATGCCGTGTGTAGATGCGCCTACGGCTACTACCAGGACGAGACAACAGGCA GATGCGAGGCCTGTAGAGTGTGCGAAGCTGGATCTGGCCTGGTGTTCAGCTGCCAAGACAAGCAGAAC ACCGTGTGCGAGGAATGCCCCGATGGCACCTATAGCGACGAGGCCAACCATGTGGATCCCTGCCTGCCAttorney Docket No. 44807-0518WO1 / P18835-01TTGTACCGTGTGTGAAGATACCGAGCGGCAGCTGCGCGAGTGTACAAGATGGGCTGATGCCGAGTGCG AAGAGATCCCTGGCAGATGGATCACCAGAAGCACACCTCCAGAGGGCAGCGATAGCACAGCCCCTTCT ACACAAGAGCCCGAGGCTCCTCCTGAGCAGGACCTGATTGCTTCTACAGTGGCTGGCGTCGTGACCAC CGTGATGGGATCTAGTCAGCCCGTGGTCACCAGAGGCACCACCGACAATCTGATCCCCGTGTACTGTA GCATCCTGGCCGCCGTGGTTGTTGGACTGGTGGCCTATATCGCCTTCAAGCGGTGGAACAGCTGA(SEQ ID NO: 114)45ECD-CAR-2 DesignCD8a SP - myc tag - CD45 ECD - CD45 TMD - CD45 JMD - Linker 2 - CD3z Signaling - 4 IBB CoStim - G4S - TM1 ID JMD - TM1 ID TMD - G4Sx3 - FMC63 - FLAG tag - E2A - tNGFR Amino Acid Sequence for 45ECD-CAR-2 MALPVTALLLPLALLLHAARPEQKLISEEDLQSPTPSPTGLTTAKMPSVPLSSDPLPTHTTAFSPAST FERENDFSETTTSLSPDNTSTQVSPDSLDNASAFNTTGVSSVQTPHLPTHADSQTPSAGTDTQTFSGS AANAKLNPTPGSNAISDVPGERSTASTFPTDPVSPLTTTLSLAHHSSAALPARTSNTTITANTSDAYL NASETTTLSPSGSAVISTTTIATTPSKPTCDEKYANITVDYLYNKETKLFTAKLNVNENVECGNNTCT NNEVHNLTECKNASVSISHNSCTAPDKTLILDVPPGVEKFQLHDCTQVEKADTTICLKWKNIETFTCD TQNITYRFQCGNMIFDNKEIKLENLEPEHEYKCDSEILYNNHKFTNASKIIKTDFGSPGEPQIIFCRS EAAHQGVITWNPPQRSFHNFTLCYIKETEKDCLNLDKNLIKYDLQNLKPYTKYVLSLHAYII KVQRN GSAAMCHFTTKSAPPSQVWNMTVSMTSDNSMHVKCRPPRDRNGPHERYHLEVEAGNTLVRNESHKNCD FRVKDLQYSTDYTFKAYFHNGDYPGEPFILHHSTSYNSKALIAFLAFLIIVTSI LLVVLYKIYDLHK KRGSGSGSGSSLRVKFSRSADAPAYQQGQNQLYNELNLGRREEYDVLDKRRGRDPEMGGKPQRRKNPQ EGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPRKRGRKKLLYIF KQPFMRPVQTTQEEDGCSCRFPEEEEGGCELGGGGSYRPARVTSTSRFLNPYVVCFIVVAGVVILAVT IALLVY FLAFDQKSYFSTLEISGGGGGSGGGGSGGGGSDIQMTQTTSSLSASLGDRVTISCRASQDIS KYLNWYQQKPDGTVKLLIYHTSRLHSGVPSRFSGSGSGTDYSLTISNLEQEDIATYFCQQGNTLPYTF GGGTKLEITGSTSGSGKPGSGEGSTKGEVKLQESGPGLVAPSQSLSVTCTVSGVSLPDYGVSWIRQPP RKGLEWLGVIWGSETTYYNSALKSRLTIIKDNSKSQVFLKMNSLQTDDTAIYYCAKHYYYGGSYAMDY WGQGTSVTVSSAAADYKDDDDKRAKRSGSGQCTNYALLKLAGDVESNPGPMGAGATGRAMDGPRLLLL LLLGVSLGGAKEACPTGLYTHSGECCKACNLGEGVAQPCGANQTVCEPCLDSVTFSDVVSATEPCKPC TECVGLQSMSAPCVEADDAVCRCAYGYYQDETTGRCEACRVCEAGSGLVFSCQDKQNTVCEECPDGTY SDEANHVDPCLPCTVCEDTERQLRECTRWADAECEEIPGRWITRSTPPEGSDSTAPSTQEPEAPPEQD LIASTVAGVVTTVMGSSQPVVTRGTTDNLIPVYCSILAAVVVGLVAYIAFKRWNS*(SEQ ID NO:22)Nucleic Acid Sequence for 45ECD-CAR-2 ATGGCTCTGCCTGTGACAGCTCTGCTGCTGCCTCTGGCTCTGCTTCTGCATGCCGCTAGACCTGAGCA GAAGCTGATCTCCGAAGAGGACCTGCAGAGCCCCACACCATCTCCAACAGGACTGACCACCGCCAAGA TGCCTAGCGTGCCCCTCTCTTCTGACCCTCTGCCTACACACACCACCGCTTTTAGCCCTGCCAGCACC TTCGAGAGAGAGAACGACTTCAGCGAGACAACCACCTCTCTGAGCCCCGACAACACCAGCACACAGGT GTCCCCAGACAGCCTGGATAATGCCAGCGCCTTCAATACCACCGGCGTGTCCTCTGTGCAGACCCCTC ATCTGCCAACACACGCCGATAGCCAGACACCTTCTGCCGGCACCGATACACAGACCTTTTCTGGCTCT GCCGCCAACGCCAAGCTGAACCCTACACCTGGCAGCAACGCCATCTCTGATGTGCCTGGCGAGAGAAG CACCGCCAGCACATTTCCAACAGACCCCGTGTCTCCCCTGACCACCACACTGTCTCTGGCCCACCATA GCTCTGCTGCCCTGCCTGCCAGAACCAGCAACACCACCATCACCGCCAATACCAGCGACGCCTACCTG AACGCCAGCGAAACCACAACACTGAGCCCTAGCGGAAGCGCCGTGATCAGCACAACCACAATCGCCACAttorney Docket No. 44807-0518WO1 / P18835-01CACACCTAGCAAGCCTACCTGCGACGAGAAGTACGCCAACATCACCGTGGACTACCTGTACAACAAAG AGACAAAGCTGTTCACGGCCAAGCTCAACGTGAACGAGAACGTGGAATGCGGCAACAATACCTGCACC AACAACGAGGTGCACAACCTGACCGAGTGCAAGAACGCCTCCGTGTCCATCAGCCACAACAGCTGCAC AGCCCCTGACAAGACCCTGATCCTGGATGTGCCTCCTGGCGTGGAAAAGTTCCAGCTGCACGATTGCA CCCAGGTGGAAAAGGCCGATACCACCATCTGCCTGAAGTGGAAGAACATCGAGACATTCACCTGTGAC ACCCAGAACATCACCTACCGGTTCCAGTGCGGCAATATGATCTTCGATAACAAAGAAATCAAGCTCGA GAACCTCGAGCCTGAGCACGAGTACAAGTGCGACAGCGAGATCCTGTATAACAATCACAAGTTCACCA ACGCCAGCAAGATCATCAAGACCGACTTCGGCTCTCCCGGCGAGCCCCAGATCATCTTCTGTAGATCT GAGGCCGCTCACCAGGGCGTGATCACCTGGAATCCTCCACAGCGGAGCTTCCACAACTTCACCCTGTG CTACATCAAAGAAACCGAGAAGGACTGCCTGAACCTGGACAAGAACCTCATTAAGTACGACCTGCAGA ACCTGAAGCCGTACACCAAATACGTGCTGAGCCTGCACGCCTACATCATTGCCAAGGTGCAGAGAAAT GGCAGCGCCGCCATGTGCCACTTCACCACAAAAAGCGCCCCTCCAAGCCAAGTGTGGAACATGACCGT GTCTATGACCAGCGACAACTCCATGCACGTGAAGTGCCGGCCTCCACGGGATAGAAATGGCCCTCACG AGAGATACCACCTGGAAGTCGAGGCCGGAAATACCCTCGTGCGGAACGAGAGCCACAAGAACTGCGAC TTCAGAGTGAAGGACCTGCAGTACAGCACCGACTACACCTTCAAGGCCTACTTCCACAATGGCGACTA CCCTGGCGAGCCCTTCATCCTGCACCACAGCACCAGCTACAACAGCAAGGCACTTATCGCGTTCCTCG CGTTTCTCATTATTGTTACATCCATAGCTTTGCTTGTTGTACTTTACAAGATTTATGACCTTCATAAG AAACGAGGATCTGGATCAGGCAGCGGAAGCTCTCTGCGCGTGAAGTTCAGCAGATCAGCCGACGCTCC TGCCTATCAGCAGGGCCAGAACCAGCTGTACAACGAGCTGAACCTGGGGAGAAGAGAAGAGTACGACG TGCTGGACAAGCGGAGAGGCAGAGATCCTGAGATGGGCGGAAAGCCCCAGCGGAGAAAGAATCCTCAA GAGGGCCTGTATAATGAGCTGCAGAAAGACAAGATGGCCGAGGCCTACAGCGAGATCGGAATGAAGGG CGAGCGCAGAAGAGGCAAGGGACACGATGGACTGTACCAGGGCCTGAGCACCGCCACCAAGGATACCT ATGATGCCCTGCACATGCAGGCCCTGCCTCCAAGAAAGCGGGGCAGAAAGAAGCTGCTGTACATCTTC AAGCAGCCCTTCATGCGGCCCGTGCAGACCACACAAGAGGAAGATGGCTGCTCCTGCAGATTCCCCGA GGAAGAAGAAGGCGGCTGCGAACTTGGAGGCGGCGGATCTTATAGACCCGCCAGAGTGACCAGCACCA GCCGGTTTCTGAACCCCTACGTCGTGTGCTTCATTGTGGTGGCCGGCGTTGTGATCCTGGCCGTGACA ATTGCCCTGCTGGTGTACTTCCTGGCCTTCGACCAGAAGTCCTACTTCAGCACCCTGGAAATCTCTGG CGGAGGCGGAGGATCTGGTGGCGGAGGAAGCGGTGGCGGCGGTTCTGACATCCAGATGACCCAGACCA CAAGCAGCCTGTCTGCCAGCCTGGGCGATAGAGTGACCATCAGCTGTAGAGCCAGCCAGGACATCAGC AAGTACCTGAACTGGTATCAGCAAAAGCCCGACGGCACCGTGAAGCTGCTGATCTACCACACCAGCAG ACTGCACAGCGGCGTGCCAAGCAGATTTTCTGGCAGCGGCTCTGGCACCGACTACAGCCTGACAATCA GCAACCTGGAACAAGAGGATATCGCTACCTACTTCTGCCAGCAAGGCAACACCCTGCCTTACACCTTT GGCGGAGGCACCAAGCTGGAAATCACCGGCTCTACAAGCGGCAGCGGCAAACCTGGATCTGGCGAGGG ATCTACCAAGGGCGAAGTGAAACTGCAAGAGTCTGGCCCTGGACTGGTGGCCCCATCTCAGTCTCTGA GCGTGACCTGTACAGTCAGCGGAGTGTCCCTGCCTGATTACGGCGTGTCCTGGATCAGACAGCCTCCT CGGAAAGGCCTGGAATGGCTGGGAGTGATCTGGGGCAGCGAGACAACCTACTACAACAGCGCCCTGAA GTCCCGGCTGACCATCATCAAGGACAACTCCAAGAGCCAGGTGTTCCTGAAGATGAACAGCCTGCAGA CCGACGACACCGCCATCTACTATTGCGCCAAGCACTACTACTACGGCGGCAGCTACGCCATGGATTAT TGGGGCCAGGGCACCAGCGTGACCGTTTCTTCTGCCGCCGCTGACTACAAGGACGACGACGACAAGCG GGCCAAACGATCTGGCTCTGGCCAGTGTACCAACTATGCCCTGCTCAAGCTCGCTGGCGACGTCGAGT CTAACCCTGGACCAATGGGAGCTGGCGCTACAGGCAGAGCTATGGATGGACCTAGACTGCTGCTGCTC CTGCTTCTGGGAGTGTCTCTTGGCGGAGCCAAAGAGGCCTGTCCTACCGGCCTGTATACACACTCTGG CGAGTGCTGCAAGGCCTGCAATCTTGGAGAAGGCGTCGCACAGCCTTGCGGCGCTAATCAGACAGTGT GCGAGCCTTGCCTGGACAGCGTGACCTTTAGCGACGTGGTGTCAGCCACCGAGCCATGCAAGCCATGT ACCGAGTGTGTGGGCCTGCAGAGCATGTCTGCCCCTTGCGTGGAAGCTGACGATGCCGTGTGTAGATG CGCCTACGGCTACTACCAGGACGAGACAACAGGCAGATGCGAGGCCTGTAGAGTGTGCGAAGCTGGAT CTGGCCTGGTGTTCAGCTGCCAAGACAAGCAGAACACCGTGTGCGAGGAATGCCCCGATGGCACCTAT AGCGACGAGGCCAACCATGTGGATCCCTGCCTGCCTTGTACCGTGTGTGAAGATACCGAGCGGCAGCT GCGCGAGTGTACAAGATGGGCTGATGCCGAGTGCGAAGAGATCCCTGGCAGATGGATCACCAGAAGCAAttorney Docket No. 44807-0518WO1 / P18835-01CACCTCCAGAGGGCAGCGATAGCACAGCCCCTTCTACACAAGAGCCCGAGGCTCCTCCTGAGCAGGAC CTGATTGCTTCTACAGTGGCTGGCGTCGTGACCACCGTGATGGGATCTAGTCAGCCCGTGGTCACCAG AGGCACCACCGACAATCTGATCCCCGTGTACTGTAGCATCCTGGCCGCCGTGGTTGTTGGACTGGTGG CCTATATCGCCTTCAAGCGGTGGAACAGCTGA(SEQ ID NO: 115)CAR-2 DesignCD8a SP - myc tag - K - CD45 TMD - CD45 JMD - Linker 2 - CD3z Signaling - 4 IBB CoStim -G4S - TM1 ID JMD - TM1 ID TMD - G4Sx3 - FMC63 - FLAG tag - E2A - tNGFRAmino Acid Sequence for CAR-2 MALPVTALLLPLALLLHAARPEQKLISEEDLQSPTPSPTGKPTCDEKYANITVDYLYNKETKLFTAKL NVNENVECGNNTCTNNEVHNLTECKNASVSISHNSCTAPDKTLILDVPPGVEKFQLHDCTQVEKADTT ICLKWKNIETFTCDTQNITYRFQCGNMIFDNKEIKLENLEPEHEYKCDSEILYNNHKFTNASKIIKTD FGSPGEPQIIFCRSEAAHQGVITWNPPQRSFHNFTLCYIKETEKDCLNLDKNLIKYDLQNLKPYTKYV LSLHAYII KVQRNGSAAMCHFTTKSAPPSQVWNMTVSMTSDNSMHVKCRPPRDRNGPHERYHLEVEA GNTLVRNESHKNCDFRVKDLQYSTDYTFKAYFHNGDYPGEPFILHHSTSYNSKALIAFLAFLIIVTSI ALLVVLYKIYDLHKKRGSGSGSGSSLRVKFSRSADAPAYQQGQNQLYNELNLGRREEYDVLDKRRGRD PEMGGKPQRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQAL PPRKRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCELGGGGSYRPARVTSTSRFLNPYVV CFIVVAGVVILAVTIALLVYFLAFDQKSYFSTLEISGGGGGSGGGGSGGGGSDIQMTQTTSSLSASLG DRVTISCRASQDISKYLNWYQQKPDGTVKLLIYHTSRLHSGVPSRFSGSGSGTDYSLTISNLEQEDIA TYFCQQGNTLPYTFGGGTKLEITGSTSGSGKPGSGEGSTKGEVKLQESGPGLVAPSQSLSVTCTVSGV SLPDYGVSWIRQPPRKGLEWLGVIWGSETTYYNSALKSRLTI IKDNSKSQVFLKMNSLQTDDTAIYYC AKHYYYGGSYAMDYWGQGTSVTVSSAAADYKDDDDKRAKRSGSGQCTNYALLKLAGDVESNPGPMGAG ATGRAMDGPRLLLLLLLGVSLGGAKEACPTGLYTHSGECCKACNLGEGVAQPCGANQTVCEPCLDSVT FSDVVSATEPCKPCTECVGLQSMSAPCVEADDAVCRCAYGYYQDETTGRCEACRVCEAGSGLVFSCQD KQNTVCEECPDGTYSDEANHVDPCLPCTVCEDTERQLRECTRWADAECEEIPGRWITRSTPPEGSDST APSTQEPEAPPEQDLIASTVAGVVTTVMGSSQPVVTRGTTDNLIPVYCSILAAVVVGLVAYIAFKRWNS*(SEQ ID NO:23)Nucleic Acid Sequence for CAR-2 ATGGCTCTGCCTGTGACAGCTCTGCTGCTGCCTCTGGCTCTGCTTCTGCATGCCGCTAGACCTGAGCA GAAGCTGATCTCCGAAGAGGACCTGCAGAGCCCCACACCATCTCCAACAGGAAAGCCTACCTGCGACG AGAAGTACGCCAACATCACCGTGGACTACCTGTACAACAAAGAGACAAAGCTGTTCACGGCCAAGCTC AACGTGAACGAGAACGTGGAATGCGGCAACAATACCTGCACCAACAACGAGGTGCACAACCTGACCGA GTGCAAGAACGCCTCCGTGTCCATCAGCCACAACAGCTGCACAGCCCCTGACAAGACCCTGATCCTGG ATGTGCCTCCTGGCGTGGAAAAGTTCCAGCTGCACGATTGCACCCAGGTGGAAAAGGCCGATACCACC ATCTGCCTGAAGTGGAAGAACATCGAGACATTCACCTGTGACACCCAGAACATCACCTACCGGTTCCA GTGCGGCAATATGATCTTCGATAACAAAGAAATCAAGCTCGAGAACCTCGAGCCTGAGCACGAGTACA AGTGCGACAGCGAGATCCTGTATAACAATCACAAGTTCACCAACGCCAGCAAGATCATCAAGACCGAC TTCGGCTCTCCCGGCGAGCCCCAGATCATCTTCTGTAGATCTGAGGCCGCTCACCAGGGCGTGATCAC CTGGAATCCTCCACAGCGGAGCTTCCACAACTTCACCCTGTGCTACATCAAAGAAACCGAGAAGGACT GCCTGAACCTGGACAAGAACCTCATTAAGTACGACCTGCAGAACCTGAAGCCGTACACCAAATACGTG CTGAGCCTGCACGCCTACATCATTGCCAAGGTGCAGAGAAATGGCAGCGCCGCCATGTGCCACTTCACAttorney Docket No. 44807-0518WO1 / P18835-01CACAAAAAGCGCCCCTCCAAGCCAAGTGTGGAACATGACCGTGTCTATGACCAGCGACAACTCCATGC ACGTGAAGTGCCGGCCTCCACGGGATAGAAATGGCCCTCACGAGAGATACCACCTGGAAGTCGAGGCC GGAAATACCCTCGTGCGGAACGAGAGCCACAAGAACTGCGACTTCAGAGTGAAGGACCTGCAGTACAG CACCGACTACACCTTCAAGGCCTACTTCCACAATGGCGACTACCCTGGCGAGCCCTTCATCCTGCACC ACAGCACCAGCTACAACAGCAAGGCACTTATCGCGTTCCTCGCGTTTCTCATTATTGTTACATCCATA GCTTTGCTTGTTGTACTTTACAAGATTTATGACCTTCATAAGAAACGAGGATCTGGATCAGGCAGCGG AAGCTCTCTGCGCGTGAAGTTCAGCAGATCAGCCGACGCTCCTGCCTATCAGCAGGGCCAGAACCAGC TGTACAACGAGCTGAACCTGGGGAGAAGAGAAGAGTACGACGTGCTGGACAAGCGGAGAGGCAGAGAT CCTGAGATGGGCGGAAAGCCCCAGCGGAGAAAGAATCCTCAAGAGGGCCTGTATAATGAGCTGCAGAA AGACAAGATGGCCGAGGCCTACAGCGAGATCGGAATGAAGGGCGAGCGCAGAAGAGGCAAGGGACACG ATGGACTGTACCAGGGCCTGAGCACCGCCACCAAGGATACCTATGATGCCCTGCACATGCAGGCCCTG CCTCCAAGAAAGCGGGGCAGAAAGAAGCTGCTGTACATCTTCAAGCAGCCCTTCATGCGGCCCGTGCA GACCACACAAGAGGAAGATGGCTGCTCCTGCAGATTCCCCGAGGAAGAAGAAGGCGGCTGCGAACTTG GAGGCGGCGGATCTTATAGACCCGCCAGAGTGACCAGCACCAGCCGGTTTCTGAACCCCTACGTCGTG TGCTTCATTGTGGTGGCCGGCGTTGTGATCCTGGCCGTGACAATTGCCCTGCTGGTGTACTTCCTGGC CTTCGACCAGAAGTCCTACTTCAGCACCCTGGAAATCTCTGGCGGAGGCGGAGGATCTGGTGGCGGAG GAAGCGGTGGCGGCGGTTCTGACATCCAGATGACCCAGACCACAAGCAGCCTGTCTGCCAGCCTGGGC GATAGAGTGACCATCAGCTGTAGAGCCAGCCAGGACATCAGCAAGTACCTGAACTGGTATCAGCAAAA GCCCGACGGCACCGTGAAGCTGCTGATCTACCACACCAGCAGACTGCACAGCGGCGTGCCAAGCAGAT TTTCTGGCAGCGGCTCTGGCACCGACTACAGCCTGACAATCAGCAACCTGGAACAAGAGGATATCGCT ACCTACTTCTGCCAGCAAGGCAACACCCTGCCTTACACCTTTGGCGGAGGCACCAAGCTGGAAATCAC CGGCTCTACAAGCGGCAGCGGCAAACCTGGATCTGGCGAGGGATCTACCAAGGGCGAAGTGAAACTGC AAGAGTCTGGCCCTGGACTGGTGGCCCCATCTCAGTCTCTGAGCGTGACCTGTACAGTCAGCGGAGTG TCCCTGCCTGATTACGGCGTGTCCTGGATCAGACAGCCTCCTCGGAAAGGCCTGGAATGGCTGGGAGT GATCTGGGGCAGCGAGACAACCTACTACAACAGCGCCCTGAAGTCCCGGCTGACCATCATCAAGGACA ACTCCAAGAGCCAGGTGTTCCTGAAGATGAACAGCCTGCAGACCGACGACACCGCCATCTACTATTGC GCCAAGCACTACTACTACGGCGGCAGCTACGCCATGGATTATTGGGGCCAGGGCACCAGCGTGACCGT TTCTTCTGCCGCCGCTGACTACAAGGACGACGACGACAAGCGGGCCAAACGATCTGGCTCTGGCCAGT GTACCAACTATGCCCTGCTCAAGCTCGCTGGCGACGTCGAGTCTAACCCTGGACCAATGGGAGCTGGC GCTACAGGCAGAGCTATGGATGGACCTAGACTGCTGCTGCTCCTGCTTCTGGGAGTGTCTCTTGGCGG AGCCAAAGAGGCCTGTCCTACCGGCCTGTATACACACTCTGGCGAGTGCTGCAAGGCCTGCAATCTTG GAGAAGGCGTCGCACAGCCTTGCGGCGCTAATCAGACAGTGTGCGAGCCTTGCCTGGACAGCGTGACC TTTAGCGACGTGGTGTCAGCCACCGAGCCATGCAAGCCATGTACCGAGTGTGTGGGCCTGCAGAGCAT GTCTGCCCCTTGCGTGGAAGCTGACGATGCCGTGTGTAGATGCGCCTACGGCTACTACCAGGACGAGA CAACAGGCAGATGCGAGGCCTGTAGAGTGTGCGAAGCTGGATCTGGCCTGGTGTTCAGCTGCCAAGAC AAGCAGAACACCGTGTGCGAGGAATGCCCCGATGGCACCTATAGCGACGAGGCCAACCATGTGGATCC CTGCCTGCCTTGTACCGTGTGTGAAGATACCGAGCGGCAGCTGCGCGAGTGTACAAGATGGGCTGATG CCGAGTGCGAAGAGATCCCTGGCAGATGGATCACCAGAAGCACACCTCCAGAGGGCAGCGATAGCACA GCCCCTTCTACACAAGAGCCCGAGGCTCCTCCTGAGCAGGACCTGATTGCTTCTACAGTGGCTGGCGT CGTGACCACCGTGATGGGATCTAGTCAGCCCGTGGTCACCAGAGGCACCACCGACAATCTGATCCCCG TGTACTGTAGCATCCTGGCCGCCGTGGTTGTTGGACTGGTGGCCTATATCGCCTTCAAGCGGTGGAAC AGCTGA(SEQ ID NO: 116)45ECD-CAR-3 DesignCD8a SP - myc tag - CD45 Dl-4 - CD45 TMD - CD45 JMD - Linker 2 - CD3z Signaling - 41BB CoStim - G4S - TM1 ID JMD - TM1 ID TMD - G4Sx3 - FMC63 - FLAG tag - E2A - tNGFRAttorney Docket No. 44807-0518WO1 / P18835-01Amino Acid Sequence for 45ECD-CAR-3 MALPVTALLLPLALLLHAARPEQKLISEEDLQSPTPSPTGKPTCDEKYANITVDYLYNKETKLFTAKL NVNENVECGNNTCTNNEVHNLTECKNASVSISHNSCTAPDKTLILDVPPGVEKFQLHDCTQVEKADTT ICLKWKNIETFTCDTQNITYRFQCGNMIFDNKEIKLENLEPEHEYKCDSEILYNNHKFTNASKIIKTD FGSPGEPQIIFCRSEAAHQGVITWNPPQRSFHNFTLCYIKETEKDCLNLDKNLIKYDLQNLKPYTKYV LSLHAYIIAKVQRNGSAAMCHFTTKSAPPSQVWNMTVSMTSDNSMHVKCRPPRDRNGPHERYHLEVEA GNTLVRNESHKNCDFRVKDLQYSTDYTFKAYFHNGDYPGEPFILHHSTSYNSKALIAFLAFLIIVTSI ALLVVLYKIYDLHKKRGSGSGSGSSLRVKFSRSADAPAYQQGQNQLYNELNLGRREEYDVLDKRRGRD PEMGGKPQRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQAL PPRKRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCELGGGGSYRPARVTSTSRFLNPYVV CFIVVAGVVILAVT IALLVYFLAFDQKSYFSTLEISGGGGGSGGGGSGGGGSDIQMTQTTSSLSASLG DRVTISCRASQDISKYLNWYQQKPDGTVKLLIYHTSRLHSGVPSRFSGSGSGTDYSLTISNLEQEDIA TYFCQQGNTLPYTFGGGTKLEITGSTSGSGKPGSGEGSTKGEVKLQESGPGLVAPSQSLSVTCTVSGV SLPDYGVSWIRQPPRKGLEWLGVIWGSETTYYNSALKSRLTI IKDNSKSQVFLKMNSLQTDDTAIYYC AKHYYYGGSYAMDYWGQGTSVTVSSAAADYKDDDDKRAKRSGSGQCTNYALLKLAGDVESNPGPMGAG ATGRAMDGPRLLLLLLLGVSLGGAKEACPTGLYTHSGECCKACNLGEGVAQPCGANQTVCEPCLDSVT FSDVVSATEPCKPCTECVGLQSMSAPCVEADDAVCRCAYGYYQDETTGRCEACRVCEAGSGLVFSCQD KQNTVCEECPDGTYSDEANHVDPCLPCTVCEDTERQLRECTRWADAECEEIPGRWITRSTPPEGSDST APSTQEPEAPPEQDLIASTVAGVVTTVMGSSQPVVTRGTTDNLIPVYCSILAAVVVGLVAYIAFKRWNS*(SEQ ID NO:24)Nucleic Acid Sequence for 45ECD-CAR-3 ATGGCTCTGCCTGTGACAGCTCTGCTGCTGCCTCTGGCTCTGCTTCTGCATGCCGCTAGACCTGAGCA GAAGCTGATCTCCGAAGAGGACCTGCAGAGCCCCACACCATCTCCAACAGGAAAGCCTACCTGCGACG AGAAGTACGCCAACATCACCGTGGACTACCTGTACAACAAAGAGACAAAGCTGTTCACGGCCAAGCTC AACGTGAACGAGAACGTGGAATGCGGCAACAATACCTGCACCAACAACGAGGTGCACAACCTGACCGA GTGCAAGAACGCCTCCGTGTCCATCAGCCACAACAGCTGCACAGCCCCTGACAAGACCCTGATCCTGG ATGTGCCTCCTGGCGTGGAAAAGTTCCAGCTGCACGATTGCACCCAGGTGGAAAAGGCCGATACCACC ATCTGCCTGAAGTGGAAGAACATCGAGACATTCACCTGTGACACCCAGAACATCACCTACCGGTTCCA GTGCGGCAATATGATCTTCGATAACAAAGAAATCAAGCTCGAGAACCTCGAGCCTGAGCACGAGTACA AGTGCGACAGCGAGATCCTGTATAACAATCACAAGTTCACCAACGCCAGCAAGATCATCAAGACCGAC TTCGGCTCTCCCGGCGAGCCCCAGATCATCTTCTGTAGATCTGAGGCCGCTCACCAGGGCGTGATCAC CTGGAATCCTCCACAGCGGAGCTTCCACAACTTCACCCTGTGCTACATCAAAGAAACCGAGAAGGACT GCCTGAACCTGGACAAGAACCTCATTAAGTACGACCTGCAGAACCTGAAGCCGTACACCAAATACGTG CTGAGCCTGCACGCCTACATCATTGCCAAGGTGCAGAGAAATGGCAGCGCCGCCATGTGCCACTTCAC CACAAAAAGCGCCCCTCCAAGCCAAGTGTGGAACATGACCGTGTCTATGACCAGCGACAACTCCATGC ACGTGAAGTGCCGGCCTCCACGGGATAGAAATGGCCCTCACGAGAGATACCACCTGGAAGTCGAGGCC GGAAATACCCTCGTGCGGAACGAGAGCCACAAGAACTGCGACTTCAGAGTGAAGGACCTGCAGTACAG CACCGACTACACCTTCAAGGCCTACTTCCACAATGGCGACTACCCTGGCGAGCCCTTCATCCTGCACC ACAGCACCAGCTACAACAGCAAGGCACTTATCGCGTTCCTCGCGTTTCTCATTATTGTTACATCCATA GCTTTGCTTGTTGTACTTTACAAGATTTATGACCTTCATAAGAAACGAGGATCTGGATCAGGCAGCGG AAGCTCTCTGCGCGTGAAGTTCAGCAGATCAGCCGACGCTCCTGCCTATCAGCAGGGCCAGAACCAGC TGTACAACGAGCTGAACCTGGGGAGAAGAGAAGAGTACGACGTGCTGGACAAGCGGAGAGGCAGAGAT CCTGAGATGGGCGGAAAGCCCCAGCGGAGAAAGAATCCTCAAGAGGGCCTGTATAATGAGCTGCAGAA AGACAAGATGGCCGAGGCCTACAGCGAGATCGGAATGAAGGGCGAGCGCAGAAGAGGCAAGGGACACG ATGGACTGTACCAGGGCCTGAGCACCGCCACCAAGGATACCTATGATGCCCTGCACATGCAGGCCCTGAttorney Docket No. 44807-0518WO1 / P18835-01CCTCCAAGAAAGCGGGGCAGAAAGAAGCTGCTGTACATCTTCAAGCAGCCCTTCATGCGGCCCGTGCA GACCACACAAGAGGAAGATGGCTGCTCCTGCAGATTCCCCGAGGAAGAAGAAGGCGGCTGCGAACTTG GAGGCGGCGGATCTTATAGACCCGCCAGAGTGACCAGCACCAGCCGGTTTCTGAACCCCTACGTCGTG TGCTTCATTGTGGTGGCCGGCGTTGTGATCCTGGCCGTGACAATTGCCCTGCTGGTGTACTTCCTGGC CTTCGACCAGAAGTCCTACTTCAGCACCCTGGAAATCTCTGGCGGAGGCGGAGGATCTGGTGGCGGAG GAAGCGGTGGCGGCGGTTCTGACATCCAGATGACCCAGACCACAAGCAGCCTGTCTGCCAGCCTGGGC GATAGAGTGACCATCAGCTGTAGAGCCAGCCAGGACATCAGCAAGTACCTGAACTGGTATCAGCAAAA GCCCGACGGCACCGTGAAGCTGCTGATCTACCACACCAGCAGACTGCACAGCGGCGTGCCAAGCAGAT TTTCTGGCAGCGGCTCTGGCACCGACTACAGCCTGACAATCAGCAACCTGGAACAAGAGGATATCGCT ACCTACTTCTGCCAGCAAGGCAACACCCTGCCTTACACCTTTGGCGGAGGCACCAAGCTGGAAATCAC CGGCTCTACAAGCGGCAGCGGCAAACCTGGATCTGGCGAGGGATCTACCAAGGGCGAAGTGAAACTGC AAGAGTCTGGCCCTGGACTGGTGGCCCCATCTCAGTCTCTGAGCGTGACCTGTACAGTCAGCGGAGTG TCCCTGCCTGATTACGGCGTGTCCTGGATCAGACAGCCTCCTCGGAAAGGCCTGGAATGGCTGGGAGT GATCTGGGGCAGCGAGACAACCTACTACAACAGCGCCCTGAAGTCCCGGCTGACCATCATCAAGGACA ACTCCAAGAGCCAGGTGTTCCTGAAGATGAACAGCCTGCAGACCGACGACACCGCCATCTACTATTGC GCCAAGCACTACTACTACGGCGGCAGCTACGCCATGGATTATTGGGGCCAGGGCACCAGCGTGACCGT TTCTTCTGCCGCCGCTGACTACAAGGACGACGACGACAAGCGGGCCAAACGATCTGGCTCTGGCCAGT GTACCAACTATGCCCTGCTCAAGCTCGCTGGCGACGTCGAGTCTAACCCTGGACCAATGGGAGCTGGC GCTACAGGCAGAGCTATGGATGGACCTAGACTGCTGCTGCTCCTGCTTCTGGGAGTGTCTCTTGGCGG AGCCAAAGAGGCCTGTCCTACCGGCCTGTATACACACTCTGGCGAGTGCTGCAAGGCCTGCAATCTTG GAGAAGGCGTCGCACAGCCTTGCGGCGCTAATCAGACAGTGTGCGAGCCTTGCCTGGACAGCGTGACC TTTAGCGACGTGGTGTCAGCCACCGAGCCATGCAAGCCATGTACCGAGTGTGTGGGCCTGCAGAGCAT GTCTGCCCCTTGCGTGGAAGCTGACGATGCCGTGTGTAGATGCGCCTACGGCTACTACCAGGACGAGA CAACAGGCAGATGCGAGGCCTGTAGAGTGTGCGAAGCTGGATCTGGCCTGGTGTTCAGCTGCCAAGAC AAGCAGAACACCGTGTGCGAGGAATGCCCCGATGGCACCTATAGCGACGAGGCCAACCATGTGGATCC CTGCCTGCCTTGTACCGTGTGTGAAGATACCGAGCGGCAGCTGCGCGAGTGTACAAGATGGGCTGATG CCGAGTGCGAAGAGATCCCTGGCAGATGGATCACCAGAAGCACACCTCCAGAGGGCAGCGATAGCACA GCCCCTTCTACACAAGAGCCCGAGGCTCCTCCTGAGCAGGACCTGATTGCTTCTACAGTGGCTGGCGT CGTGACCACCGTGATGGGATCTAGTCAGCCCGTGGTCACCAGAGGCACCACCGACAATCTGATCCCCG TGTACTGTAGCATCCTGGCCGCCGTGGTTGTTGGACTGGTGGCCTATATCGCCTTCAAGCGGTGGAAC AGCTGA(SEQ ID NO: 117)19CAR DesignCD3z Signaling - 41BB CoStim - G4S - TM1 ID JMD - TM1 ID TMD - G4Sx3 - FMC63 - FLAG tag - E2A - tNGFRAmino Acid Sequence for 19CAR MRVKFSRSADAPAYQQGQNQLYNELNLGRREEYDVLDKRRGRDPEMGGKPQRRKNPQEGLYNELQKDK MAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPRKRGRKKLLYIFKQPFMRPVQTT QEEDGCSCRFPEEEEGGCELGGGGSYRPARVTSTSRFLNPYVVCFIVVAGVVILAVTIALLVYFLAFD QKSYFSTLEISGGGGGSGGGGSGGGGSDIQMTQTTSSLSASLGDRVTISCRASQDISKYLNWYQQKPD GTVKLLIYHTSRLHSGVPSRFSGSGSGTDYSLTISNLEQEDIATYFCQQGNTLPYTFGGGTKLEITGS TSGSGKPGSGEGSTKGEVKLQESGPGLVAPSQSLSVTCTVSGVSLPDYGVSWIRQPPRKGLEWLGVIW GSETTYYNSALKSRLTIIKDNSKSQVFLKMNSLQTDDTAIYYCAKHYYYGGSYAMDYWGQGTSVTVSS AAADYKDDDDKRAKRSGSGQCTNYALLKLAGDVESNPGPMGAGATGRAMDGPRLLLLLLLGVSLGGAK EACPTGLYTHSGECCKACNLGEGVAQPCGANQTVCEPCLDSVTFSDVVSATEPCKPCTECVGLQSMSAAttorney Docket No. 44807-0518WO1 / P18835-01PCVEADDAVCRCAYGYYQDETTGRCEACRVCEAGSGLVFSCQDKQNTVCEECPDGTYSDEANHVDPCL PCTVCEDTERQLRECTRWADAECEEIPGRWITRSTPPEGSDSTAPSTQEPEAPPEQDLIASTVAGVVT TVMGSSQPVVTRGTTDNLIPVYCSILAAVVVGLVAYIAFKRWNS*(SEQ ID NO:25)Nucleic Acid Sequence for 19CAR ATGCGCGTGAAGTTCAGCAGATCAGCCGACGCTCCTGCCTATCAGCAGGGCCAGAACCAGCTGTACAA CGAGCTGAACCTGGGGAGAAGAGAAGAGTACGACGTGCTGGACAAGCGGAGAGGCAGAGATCCTGAGA TGGGCGGAAAGCCCCAGCGGAGAAAGAATCCTCAAGAGGGCCTGTATAATGAGCTGCAGAAAGACAAG ATGGCCGAGGCCTACAGCGAGATCGGAATGAAGGGCGAGCGCAGAAGAGGCAAGGGACACGATGGACT GTACCAGGGCCTGAGCACCGCCACCAAGGATACCTATGATGCCCTGCACATGCAGGCCCTGCCTCCAA GAAAGCGGGGCAGAAAGAAGCTGCTGTACATCTTCAAGCAGCCCTTCATGCGGCCCGTGCAGACCACA CAAGAGGAAGATGGCTGCTCCTGCAGATTCCCCGAGGAAGAAGAAGGCGGCTGCGAACTTGGAGGCGG CGGATCTTATAGACCCGCCAGAGTGACCAGCACCAGCCGGTTTCTGAACCCCTACGTCGTGTGCTTCA TTGTGGTGGCCGGCGTTGTGATCCTGGCCGTGACAATTGCCCTGCTGGTGTACTTCCTGGCCTTCGAC CAGAAGTCCTACTTCAGCACCCTGGAAATCTCTGGCGGAGGCGGAGGATCTGGTGGCGGAGGAAGCGG TGGCGGCGGTTCTGACATCCAGATGACCCAGACCACAAGCAGCCTGTCTGCCAGCCTGGGCGATAGAG TGACCATCAGCTGTAGAGCCAGCCAGGACATCAGCAAGTACCTGAACTGGTATCAGCAAAAGCCCGAC GGCACCGTGAAGCTGCTGATCTACCACACCAGCAGACTGCACAGCGGCGTGCCAAGCAGATTTTCTGG CAGCGGCTCTGGCACCGACTACAGCCTGACAATCAGCAACCTGGAACAAGAGGATATCGCTACCTACT TCTGCCAGCAAGGCAACACCCTGCCTTACACCTTTGGCGGAGGCACCAAGCTGGAAATCACCGGCTCT ACAAGCGGCAGCGGCAAACCTGGATCTGGCGAGGGATCTACCAAGGGCGAAGTGAAACTGCAAGAGTC TGGCCCTGGACTGGTGGCCCCATCTCAGTCTCTGAGCGTGACCTGTACAGTCAGCGGAGTGTCCCTGC CTGATTACGGCGTGTCCTGGATCAGACAGCCTCCTCGGAAAGGCCTGGAATGGCTGGGAGTGATCTGG GGCAGCGAGACAACCTACTACAACAGCGCCCTGAAGTCCCGGCTGACCATCATCAAGGACAACTCCAA GAGCCAGGTGTTCCTGAAGATGAACAGCCTGCAGACCGACGACACCGCCATCTACTATTGCGCCAAGC ACTACTACTACGGCGGCAGCTACGCCATGGATTATTGGGGCCAGGGCACCAGCGTGACCGTTTCTTCT GCCGCCGCTGACTACAAGGACGACGACGACAAGCGGGCCAAACGATCTGGCTCTGGCCAGTGTACCAA CTATGCCCTGCTCAAGCTCGCTGGCGACGTCGAGTCTAACCCTGGACCAATGGGAGCTGGCGCTACAG GCAGAGCTATGGATGGACCTAGACTGCTGCTGCTCCTGCTTCTGGGAGTGTCTCTTGGCGGAGCCAAA GAGGCCTGTCCTACCGGCCTGTATACACACTCTGGCGAGTGCTGCAAGGCCTGCAATCTTGGAGAAGG CGTCGCACAGCCTTGCGGCGCTAATCAGACAGTGTGCGAGCCTTGCCTGGACAGCGTGACCTTTAGCG ACGTGGTGTCAGCCACCGAGCCATGCAAGCCATGTACCGAGTGTGTGGGCCTGCAGAGCATGTCTGCC CCTTGCGTGGAAGCTGACGATGCCGTGTGTAGATGCGCCTACGGCTACTACCAGGACGAGACAACAGG CAGATGCGAGGCCTGTAGAGTGTGCGAAGCTGGATCTGGCCTGGTGTTCAGCTGCCAAGACAAGCAGA ACACCGTGTGCGAGGAATGCCCCGATGGCACCTATAGCGACGAGGCCAACCATGTGGATCCCTGCCTG CCTTGTACCGTGTGTGAAGATACCGAGCGGCAGCTGCGCGAGTGTACAAGATGGGCTGATGCCGAGTG CGAAGAGATCCCTGGCAGATGGATCACCAGAAGCACACCTCCAGAGGGCAGCGATAGCACAGCCCCTT CTACACAAGAGCCCGAGGCTCCTCCTGAGCAGGACCTGATTGCTTCTACAGTGGCTGGCGTCGTGACC ACCGTGATGGGATCTAGTCAGCCCGTGGTCACCAGAGGCACCACCGACAATCTGATCCCCGTGTACTG TAGCATCCTGGCCGCCGTGGTTGTTGGACTGGTGGCCTATATCGCCTTCAAGCGGTGGAACAGCTGA(SEQ ID NO: 118)A2CAR DesignCD3z Signaling - 41BB CoStim - G4S - TM1 ID JMD - TM1 ID TMD - G4Sx3 - BB7.2 - FLAG tag -E2A - tNGFRAttorney Docket No. 44807-0518WO1 / P18835-01Amino Acid Sequence for A2CAR MRVKFSRSADAPAYQQGQNQLYNELNLGRREEYDVLDKRRGRDPEMGGKPQRRKNPQEGLYNELQKDK MAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPRKRGRKKLLYIFKQPFMRPVQTT QEEDGCSCRFPEEEEGGCELGGGGSYRPARVTSTSRFLNPYVVCFIVVAGVVILAVTIALLVYFLAFD QKSYFSTLEISGGGGGSGGGGSGGGGSQVQLQQSGPELVKPGASVKMSCKASGYTFTSYHIQWVKQRP GQGLEWIGWIYPGDGSTQYNEKFKGKTTLTADKSSSTAYMLLSSLTSEDSAIYFCAREGTYYAMDYWG QGTSVTVSSGGGGSGGGGSGGGGSDIVMTQAPLSLPVSLGDQVSISCRSSQSIVHSNGNTYLEWYLQK PGQSPKLLIYKVSNRFSGVPDRFSGSGSGTDFTLKISRVEAEDLGVYYCFQGSHVPRT FGGGTKLELK RTDYKDDDDKRAKRSGSGQCTNYALLKLAGDVESNPGPMGAGATGRAMDGPRLLLLLLLGVSLGGAKE ACPTGLYTHSGECCKACNLGEGVAQPCGANQTVCEPCLDSVTFSDVVSATEPCKPCTECVGLQSMSAP CVEADDAVCRCAYGYYQDETTGRCEACRVCEAGSGLVFSCQDKQNTVCEECPDGTYSDEANHVDPCLP CTVCEDTERQLRECTRWADAECEEIPGRWITRSTPPEGSDSTAPSTQEPEAPPEQDLIASTVAGVVTT VMG S S Q P V VT RGTTDNLIPVYCSI L AAV VVGL VAY I AF KRWN S *(SEQ ID NO:26)Nucleic Acid Sequence for A2CAR ATGCGCGTGAAGTTCAGCAGATCAGCCGACGCTCCTGCCTATCAGCAGGGCCAGAACCAGCTGTACAA CGAGCTGAACCTGGGGAGAAGAGAAGAGTACGACGTGCTGGACAAGCGGAGAGGCAGAGATCCTGAGA TGGGCGGAAAGCCCCAGCGGAGAAAGAATCCTCAAGAGGGCCTGTATAATGAGCTGCAGAAAGACAAG ATGGCCGAGGCCTACAGCGAGATCGGAATGAAGGGCGAGCGCAGAAGAGGCAAGGGACACGATGGACT GTACCAGGGCCTGAGCACCGCCACCAAGGATACCTATGATGCCCTGCACATGCAGGCCCTGCCTCCAA GAAAGCGGGGCAGAAAGAAGCTGCTGTACATCTTCAAGCAGCCCTTCATGCGGCCCGTGCAGACCACA CAAGAGGAAGATGGCTGCTCCTGCAGATTCCCCGAGGAAGAAGAAGGCGGCTGCGAACTTGGAGGCGG CGGATCTTATAGACCCGCCAGAGTGACCAGCACCAGCCGGTTTCTGAACCCCTACGTCGTGTGCTTCA TTGTGGTGGCCGGCGTTGTGATCCTGGCCGTGACAATTGCCCTGCTGGTGTACTTCCTGGCCTTCGAC CAGAAGTCCTACTTCAGCACCCTGGAAATCTCTGGCGGAGGCGGAGGATCTGGTGGCGGAGGAAGCGG TGGCGGCGGTTCTCAGGTTCAGCTGCAGCAGTCTGGACCTGAGCTGGTTAAGCCTGGCGCTTCCGTGA AGATGAGCTGCAAGGCCAGCGGCTACACCTTCACCAGCTACCACATCCAGTGGGTCAAGCAGAGGCCT GGACAGGGACTCGAGTGGATCGGCTGGATCTATCCTGGCGACGGCAGCACCCAGTACAACGAGAAGTT CAAGGGCAAGACCACACTGACCGCCGACAAGAGCAGCAGCACAGCCTACATGCTGCTGAGCAGCCTGA CCAGCGAGGACAGCGCCATCTACTTTTGTGCCAGAGAGGGCACCTACTACGCCATGGATTATTGGGGC CAGGGCACCAGCGTGACAGTCTCTTCTGGTGGCGGAGGATCTGGCGGAGGTGGAAGCGGCGGAGGCGG ATCTGATATCGTGATGACACAGGCCCCTCTGAGCCTGCCTGTGTCTCTGGGAGATCAGGTGTCCATCA GCTGTCGGAGCAGCCAGAGCATCGTGCACAGCAACGGCAACACCTACCTGGAATGGTATCTGCAGAAG CCCGGACAGAGCCCCAAGCTGCTGATCTACAAGGTGTCCAACCGGTTCAGCGGCGTGCCCGATAGATT TTCTGGCTCTGGCAGCGGCACCGACTTCACCCTGAAGATCTCTAGAGTGGAAGCCGAGGACCTGGGCG TGTACTACTGCTTCCAAGGCAGCCACGTGCCAAGAACCTTTGGCGGCGGAACAAAGCTGGAACTGAAG CGGACAGACTACAAGGACGACGACGACAAGCGGGCCAAACGATCTGGCTCTGGCCAGTGTACCAACTA TGCCCTGCTCAAGCTCGCTGGCGACGTCGAGTCTAACCCTGGACCAATGGGAGCTGGCGCTACAGGCA GAGCTATGGATGGACCTAGACTGCTGCTGCTCCTGCTTCTGGGAGTGTCTCTTGGCGGAGCCAAAGAG GCCTGTCCTACCGGCCTGTATACACACTCTGGCGAGTGCTGCAAGGCCTGCAATCTTGGAGAAGGCGT CGCACAGCCTTGCGGCGCTAATCAGACAGTGTGCGAGCCTTGCCTGGACAGCGTGACCTTTAGCGACG TGGTGTCAGCCACCGAGCCATGCAAGCCATGTACCGAGTGTGTGGGCCTGCAGAGCATGTCTGCCCCT TGCGTGGAAGCTGACGATGCCGTGTGTAGATGCGCCTACGGCTACTACCAGGACGAGACAACAGGCAG ATGCGAGGCCTGTAGAGTGTGCGAAGCTGGATCTGGCCTGGTGTTCAGCTGCCAAGACAAGCAGAACA CCGTGTGCGAGGAATGCCCCGATGGCACCTATAGCGACGAGGCCAACCATGTGGATCCCTGCCTGCCT TGTACCGTGTGTGAAGATACCGAGCGGCAGCTGCGCGAGTGTACAAGATGGGCTGATGCCGAGTGCGAAttorney Docket No. 44807-0518WO1 / P18835-01AGAGATCCCTGGCAGATGGATCACCAGAAGCACACCTCCAGAGGGCAGCGATAGCACAGCCCCTTCTA CACAAGAGCCCGAGGCTCCTCCTGAGCAGGACCTGATTGCTTCTACAGTGGCTGGCGTCGTGACCACC GTGATGGGATCTAGTCAGCCCGTGGTCACCAGAGGCACCACCGACAATCTGATCCCCGTGTACTGTAG CATCCTGGCCGCCGTGGTTGTTGGACTGGTGGCCTATATCGCCTTCAAGCGGTGGAACAGCTGA(SEQ ID NO: 119)EGFRCAR DesignCD3z Signaling - CD28 CoStim - 41BB CoStim - G4S - TM1 ID JMD - TM1 ID TMD - G4Sx3 - Cetux - FLAG tag - E2A - tNGFRAmino Acid Sequence for EGFRCAR MRVKFSRSADAPAYQQGQNQLYNELNLGRREEYDVLDKRRGRDPEMGGKPQRRKNPQEGLYNELQKDK MAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPRRSKRSRLLHSDYMNMTPRRPGP TRKHYQPYAPPRDFAAYRSKRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCELGGGGSYR PARVTSTSRFLNPYVVCFIVVAGVVILAVTIALLVYFLAFDQKSYFSTLEISGGGGGSGGGGSGGGGS QVQLKQSGPGLVQPSQSLSITCTVSGFSLTNYGVHWVRQSPGKGLEWLGVIWSGGNTDYNTPFTSRLS INKDNSKSQVFFKMNSLQSNDTAIYYCARALTYYDYEFAYWGQGTLVTVSAGGGGSGGGGSGGGGSDI LLTQSPVILSVSPGERVSFSCRASQSIGTNIHWYQQRTNGSPRLLIKYASESISGIPSRFSGSGSGTD FTLSINSVESEDIADYYCQQNNNWPTTFGAGTKLELKDYKDDDDKRAKRSGSGQCTNYALLKLAGDVE SNPGPMGAGATGRAMDGPRLLLLLLLGVSLGGAKEACPTGLYTHSGECCKACNLGEGVAQPCGANQTV CEPCLDSVTFSDVVSATEPCKPCTECVGLQSMSAPCVEADDAVCRCAYGYYQDETTGRCEACRVCEAG SGLVFSCQDKQNTVCEECPDGTYSDEANHVDPCLPCTVCEDTERQLRECTRWADAECEEIPGRWITRS TPPEGSDSTAPSTQEPEAPPEQDLIASTVAGVVTTVMGSSQPVVTRGTTDNLIPVYCSILAAVVVGLV AYIAFKRWNS (SEQ ID NO: 146)Nucleic Acid Sequence for EGFRCAR ATGCGCGTGAAGTTCAGCAGATCAGCCGACGCTCCTGCCTATCAGCAGGGCCAGAACCAGCTGTACAA CGAGCTGAACCTGGGGAGAAGAGAAGAGTACGACGTGCTGGACAAGCGGAGAGGCAGAGATCCTGAGA TGGGCGGAAAGCCCCAGCGGAGAAAGAATCCTCAAGAGGGCCTGTATAATGAGCTGCAGAAAGACAAG ATGGCCGAGGCCTACAGCGAGATCGGAATGAAGGGCGAGCGCAGAAGAGGCAAGGGACACGATGGACT GTACCAGGGCCTGAGCACCGCCACCAAGGATACCTATGATGCCCTGCACATGCAGGCCCTGCCTCCAA GACGAAGCAAGCGGAGCCGGCTGCTGCACAGCGACTACATGAACATGACCCCTAGACGGCCCGGACCT ACCAGAAAGCACTACCAGCCTTACGCTCCTCCTAGAGATTTCGCCGCCTACCGGTCCAAGCGGGGCAG AAAGAAGCTGCTGTACATCTTCAAGCAGCCCTTCATGCGGCCCGTGCAGACCACACAAGAGGAAGATG GCTGCTCCTGCAGATTCCCCGAGGAAGAAGAAGGCGGCTGCGAACTTGGAGGCGGCGGATCTTATAGA CCCGCCAGAGTGACCAGCACCAGCCGGTTTCTGAACCCCTACGTCGTGTGCTTCATTGTGGTGGCCGG CGTTGTGATCCTGGCCGTGACAATTGCCCTGCTGGTGTACTTCCTGGCCTTCGACCAGAAGTCCTACT TCAGCACCCTGGAAATCTCTGGCGGAGGCGGAGGATCTGGTGGCGGAGGAAGCGGTGGCGGCGGTTCT CAAGTTCAGCTCAAGCAGTCTGGCCCTGGCCTGGTTCAGCCTAGCCAGAGCCTGAGCATCACCTGTAC CGTGTCCGGCTTCAGCCTGACCAATTACGGCGTGCACTGGGTCCGACAGAGCCCTGGAAAAGGACTGGAttorney Docket No. 44807-0518WO1 / P18835-01AATGGCTGGGAGTGATTTGGAGCGGCGGCAACACCGACTACAACACCCCATTCACCAGCAGACTGTCC ATCAACAAGGACAACAGCAAGAGCCAGGTGTTCTTCAAGATGAACAGCCTGCAGAGCAACGACACCGC CATCTACTACTGCGCTAGAGCCCTGACCTACTACGACTACGAGTTCGCCTATTGGGGCCAGGGCACAC TGGTTACAGTTTCTGCAGGCGGCGGTGGTAGTGGCGGTGGTGGTTCAGGCGGTGGCGGATCTGATATC CTGCTGACACAGAGCCCCGTGATCCTGTCTGTGTCTCCTGGCGAGAGAGTGTCCTTCAGCTGTAGAGC CAGCCAGTCCATCGGCACCAACATCCACTGGTATCAGCAGCGGACCAACGGCAGCCCTCGGCTGCTGA TTAAGTACGCCAGCGAGAGCATCAGCGGCATCCCCAGCAGATTTTCTGGCAGCGGCTCTGGCACCGAC TTCACCCTGTCTATCAACAGCGTGGAAAGCGAGGATATCGCCGATTACTACTGCCAGCAGAACAACAA CTGGCCCACCACCTTTGGAGCCGGCACCAAGCTGGAACTGAAGGACTACAAGGACGACGACGACAAGC GGGCCAAACGATCTGGCTCTGGCCAGTGTACCAACTATGCCCTGCTCAAGCTCGCTGGCGACGTCGAG TCTAACCCTGGACCAATGGGAGCTGGCGCTACAGGCAGAGCTATGGATGGACCTAGACTGCTGCTGCT CCTGCTTCTGGGAGTGTCTCTTGGCGGAGCCAAAGAGGCCTGTCCTACCGGCCTGTATACACACTCTG GCGAGTGCTGCAAGGCCTGCAATCTTGGAGAAGGCGTCGCACAGCCTTGCGGCGCTAATCAGACAGTG TGCGAGCCTTGCCTGGACAGCGTGACCTTTAGCGACGTGGTGTCAGCCACCGAGCCATGCAAGCCATG TACCGAGTGTGTGGGCCTGCAGAGCATGTCTGCCCCTTGCGTGGAAGCTGACGATGCCGTGTGTAGAT GCGCCTACGGCTACTACCAGGACGAGACAACAGGCAGATGCGAGGCCTGTAGAGTGTGCGAAGCTGGA TCTGGCCTGGTGTTCAGCTGCCAAGACAAGCAGAACACCGTGTGCGAGGAATGCCCCGATGGCACCTA TAGCGACGAGGCCAACCATGTGGATCCCTGCCTGCCTTGTACCGTGTGTGAAGATACCGAGCGGCAGC TGCGCGAGTGTACAAGATGGGCTGATGCCGAGTGCGAAGAGATCCCTGGCAGATGGATCACCAGAAGC ACACCTCCAGAGGGCAGCGATAGCACAGCCCCTTCTACACAAGAGCCCGAGGCTCCTCCTGAGCAGGA CCTGATTGCTTCTACAGTGGCTGGCGTCGTGACCACCGTGATGGGATCTAGTCAGCCCGTGGTCACCA GAGGCACCACCGACAATCTGATCCCCGTGTACTGTAGCATCCTGGCCGCCGTGGTTGTTGGACTGGTG GCCTATATCGCCTTCAAGCGGTGGAACAGCTGA(SEQ ID NO: 147)HER2CAR DesignCD3z Signaling - CD28 CoStim - 41BB CoStim - G4S - TM1 ID JMD - TM1 ID TMD - G4Sx3 - Hl 0-2-G3 - FLAG tag - E2A - tNGFRAmino Acid Sequence for HER2CAR MRVKFSRSADAPAYQQGQNQLYNELNLGRREEYDVLDKRRGRDPEMGGKPQRRKNPQEGLYNELQKDK MAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPRRSKRSRLLHSDYMNMTPRRPGP TRKHYQPYAPPRDFAAYRSKRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCELGGGGSYR PARVTSTSRFLNPYVVCFIVVAGVVILAVTIALLVYFLAFDQKSYFSTLEISGGGGGSGGGGSGGGGS DLGKKLLEAARAGQDDEVRILMANGADVNAKDEYGLTPLYLATAHGHLEIVEVLLKNGADVNAVDAIG FTPLHLAAFIGHLEIAEVLLKHGADVNAQDKFGKTAFDISIGNGNEDLAEILQKLNDYKDDDDKRAKR SGSGQCTNYALLKLAGDVESNPGPMGAGATGRAMDGPRLLLLLLLGVSLGGAKEACPTGLYTHSGECC KACNLGEGVAQPCGANQTVCEPCLDSVTFSDVVSATEPCKPCTECVGLQSMSAPCVEADDAVCRCAYG YYQDETTGRCEACRVCEAGSGLVFSCQDKQNTVCEECPDGTYSDEANHVDPCLPCTVCEDTERQLREC TRWADAECEEIPGRWITRSTPPEGSDSTAPSTQEPEAPPEQDLIASTVAGVVTTVMGSSQPVVTRGTT DNLIPVYCSILAAVVVGLVAYIAFKRWNS (SEQ ID NO: 148)Attorney Docket No. 44807-0518WO1 / P18835-01Nucleic Acid Sequence for HER2CAR ATGCGCGTGAAGTTCAGCAGATCAGCCGACGCTCCTGCCTATCAGCAGGGCCAGAACCAGCTGTACAA CGAGCTGAACCTGGGGAGAAGAGAAGAGTACGACGTGCTGGACAAGCGGAGAGGCAGAGATCCTGAGA TGGGCGGAAAGCCCCAGCGGAGAAAGAATCCTCAAGAGGGCCTGTATAATGAGCTGCAGAAAGACAAG ATGGCCGAGGCCTACAGCGAGATCGGAATGAAGGGCGAGCGCAGAAGAGGCAAGGGACACGATGGACT GTACCAGGGCCTGAGCACCGCCACCAAGGATACCTATGATGCCCTGCACATGCAGGCCCTGCCTCCAA GACGAAGCAAGCGGAGCCGGCTGCTGCACAGCGACTACATGAACATGACCCCTAGACGGCCCGGACCT ACCAGAAAGCACTACCAGCCTTACGCTCCTCCTAGAGATTTCGCCGCCTACCGGTCCAAGCGGGGCAG AAAGAAGCTGCTGTACATCTTCAAGCAGCCCTTCATGCGGCCCGTGCAGACCACACAAGAGGAAGATG GCTGCTCCTGCAGATTCCCCGAGGAAGAAGAAGGCGGCTGCGAACTTGGAGGCGGCGGATCTTATAGA CCCGCCAGAGTGACCAGCACCAGCCGGTTTCTGAACCCCTACGTCGTGTGCTTCATTGTGGTGGCCGG CGTTGTGATCCTGGCCGTGACAATTGCCCTGCTGGTGTACTTCCTGGCCTTCGACCAGAAGTCCTACT TCAGCACCCTGGAAATCTCTGGCGGAGGCGGAGGATCTGGTGGCGGAGGAAGCGGTGGCGGCGGTTCT GATCTGGGAAAGAAGCTGCTGGAAGCCGCCAGAGCCGGACAGGATGATGAAGTGCGGATCCTGATGGC CAACGGCGCCGATGTGAATGCCAAGGACGAGTACGGACTGACCCCTCTGTATCTGGCCACAGCTCACG GCCACCTGGAAATTGTGGAAGTGCTGCTGAAGAATGGGGCCGACGTGAACGCCGTGGATGCCATCGGT TTTACCCCTCTGCACCTGGCTGCCTTCATCGGCCATCTCGAAATTGCCGAGGTCCTGCTGAAGCACGG CGCTGATGTTAACGCCCAGGATAAGTTCGGCAAGACCGCCTTCGACATCAGCATCGGCAACGGCAACG AAGATCTGGCCGAGATCCTGCAGAAACTGAACGACTACAAGGACGACGACGACAAGCGGGCCAAACGA TCTGGCTCTGGCCAGTGTACCAACTATGCCCTGCTCAAGCTCGCTGGCGACGTCGAGTCTAACCCTGG ACCAATGGGAGCTGGCGCTACAGGCAGAGCTATGGATGGACCTAGACTGCTGCTGCTCCTGCTTCTGG GAGTGTCTCTTGGCGGAGCCAAAGAGGCCTGTCCTACCGGCCTGTATACACACTCTGGCGAGTGCTGC AAGGCCTGCAATCTTGGAGAAGGCGTCGCACAGCCTTGCGGCGCTAATCAGACAGTGTGCGAGCCTTG CCTGGACAGCGTGACCTTTAGCGACGTGGTGTCAGCCACCGAGCCATGCAAGCCATGTACCGAGTGTG TGGGCCTGCAGAGCATGTCTGCCCCTTGCGTGGAAGCTGACGATGCCGTGTGTAGATGCGCCTACGGC TACTACCAGGACGAGACAACAGGCAGATGCGAGGCCTGTAGAGTGTGCGAAGCTGGATCTGGCCTGGT GTTCAGCTGCCAAGACAAGCAGAACACCGTGTGCGAGGAATGCCCCGATGGCACCTATAGCGACGAGG CCAACCATGTGGATCCCTGCCTGCCTTGTACCGTGTGTGAAGATACCGAGCGGCAGCTGCGCGAGTGT ACAAGATGGGCTGATGCCGAGTGCGAAGAGATCCCTGGCAGATGGATCACCAGAAGCACACCTCCAGA GGGCAGCGATAGCACAGCCCCTTCTACACAAGAGCCCGAGGCTCCTCCTGAGCAGGACCTGATTGCTT CTACAGTGGCTGGCGTCGTGACCACCGTGATGGGATCTAGTCAGCCCGTGGTCACCAGAGGCACCACC GACAATCTGATCCCCGTGTACTGTAGCATCCTGGCCGCCGTGGTTGTTGGACTGGTGGCCTATATCGC CTTCAAGCGGTGGAACAGCTGA(SEQ ID NO: 149)HER2CAR-MC DesignCD3z Signaling - CD28 CoStim - 41BB CoStim - G4S - TM1 ID JMD - TM1 ID TMD v2 - NZ Leucine Zipper - G4Sx3 - H10-2-G3 - FLAG tag - P2A - CD8a SP - V5 tag - CZ Leucine Zipper - LZ Hinge - CD28 TMD - MyD88CD40 CoStim CD3z - E2A - tNGFRAmino Acid Sequence for HER2CAR-MC MRVKFSRSADAPAYQQGQNQLYNELNLGRREEYDVLDKRRGRDPEMGGKPQRRKNPQEGLYNELQKDK MAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPRRSKRSRLLHSDYMNMTPRRPGP TRKHYQPYAPPRDFAAYRSKRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCELGGGGSYR PARVTSTSRFLNPYVVCFIVVAGVVILAVTIALLVYFLAFDQKSYFGSGGSGALKKELQANKKELAQLAttorney Docket No. 44807-0518WO1 / P18835-01KWELQALKKELAQGGGGSGGGGSGGGGSDLGKKLLEAARAGQDDEVRILMANGADVNAKDEYGLTPLY LATAHGHLEIVEVLLKNGADVNAVDAIGFTPLHLAAFIGHLEIAEVLLKHGADVNAQDKFGKTAFDIS IGNGNEDLAEILQKLNDYKDDDDKRAKRSGSGATNFSLLKQAGDVEENPGPMALPVTALLLPLALLLH AARPGKPIPNPLLGLDSTEQLEKKLQALEKKLAQLEWKNQALEKKLAQGSGGSGRGLDFACDFWVLVV VGGVLACYSLLVTVAFIIFWVMAAGGPGAGSAAPVSSTSSLPLAALNMRVRRRLSLFLNVRTQVAADW TALAEEMDFEYLEIRQLETQADPTGRLLDAWQGRPGASVGRLLELLTKLGRDDVLLELGPSIEEDCQK YILKQQQEEAEKPLQVAAVDSSVPRTAELAGITTLDDPLGKKVAKKPTNKAPHPKQEPQEINFPDDLP GSNTAAPVQETLHGCQPVTQEDGKESRISVQERQRVKFSRSADAPAYQQGQNQLYNELNLGRREEYDV LDKRRGRDPEMGGKPQRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTY DALHMQALPPRRAKRSGSGQCTNYALLKLAGDVESNPGPMGAGATGRAMDGPRLLLLLLLGVSLGGAK EACPTGLYTHSGECCKACNLGEGVAQPCGANQTVCEPCLDSVTFSDVVSATEPCKPCTECVGLQSMSA PCVEADDAVCRCAYGYYQDETTGRCEACRVCEAGSGLVFSCQDKQNTVCEECPDGTYSDEANHVDPCL PCTVCEDTERQLRECTRWADAECEEIPGRWITRSTPPEGSDSTAPSTQEPEAPPEQDLIASTVAGVVT TVMGSSQPVVTRGTTDNLIPVYCSILAAVVVGLVAYIAFKRWNS (SEQ ID NO: 150) Nucleic Acid Sequence for HER2CAR-MC ATGCGCGTGAAGTTCAGCAGATCAGCCGACGCTCCTGCCTATCAGCAGGGCCAGAACCAGCTGTACAA CGAGCTGAACCTGGGGAGAAGAGAAGAGTACGACGTGCTGGACAAGCGGAGAGGCAGAGATCCTGAGA TGGGCGGAAAGCCCCAGCGGAGAAAGAATCCTCAAGAGGGCCTGTATAATGAGCTGCAGAAAGACAAG ATGGCCGAGGCCTACAGCGAGATCGGAATGAAGGGCGAGCGCAGAAGAGGCAAGGGACACGATGGACT GTACCAGGGCCTGAGCACCGCCACCAAGGATACCTATGATGCCCTGCACATGCAGGCCCTGCCTCCAA GACGAAGCAAGCGGAGCCGGCTGCTGCACAGCGACTACATGAACATGACCCCTAGACGGCCCGGACCT ACCAGAAAGCACTACCAGCCTTACGCTCCTCCTAGAGATTTCGCCGCCTACCGGTCCAAGCGGGGCAG AAAGAAGCTGCTGTACATCTTCAAGCAGCCCTTCATGCGGCCCGTGCAGACCACACAAGAGGAAGATG GCTGCTCCTGCAGATTCCCCGAGGAAGAAGAAGGCGGCTGCGAACTTGGAGGCGGCGGATCTTATAGA CCCGCCAGAGTGACCAGCACCAGCCGGTTTCTGAACCCCTACGTCGTGTGCTTCATTGTGGTGGCCGG CGTTGTGATCCTGGCCGTGACAATTGCCCTGCTGGTGTACTTCCTGGCCTTCGACCAGAAGTCCTACT TCGGATCAGGCGGAAGCGGAGCCCTGAAGAAAGAACTGCAGGCCAACAAGAAAGAGCTGGCCCAGCTG AAGTGGGAGCTGCAGGCTCTGAAGAAAGAGCTTGCTCAAGGAGGCGGAGGATCTGGTGGCGGAGGAAG CGGTGGCGGCGGTTCTGATCTGGGAAAGAAGCTGCTGGAAGCCGCCAGAGCCGGACAGGATGATGAAG TGCGGATCCTGATGGCCAACGGCGCCGATGTGAATGCCAAGGACGAGTACGGACTGACCCCTCTGTAT CTGGCCACAGCTCACGGCCACCTGGAAATTGTGGAAGTGCTGCTGAAGAATGGGGCCGACGTGAACGC CGTGGATGCCATCGGTTTTACCCCTCTGCACCTGGCTGCCTTCATCGGCCATCTCGAAATTGCCGAGG TCCTGCTGAAGCACGGCGCTGATGTTAACGCCCAGGATAAGTTCGGCAAGACCGCCTTCGACATCAGC ATCGGCAACGGCAACGAAGATCTGGCCGAGATCCTGCAGAAACTGAACGACTACAAGGACGACGACGA CAAGCGGGCCAAGAGAAGTGGTAGCGGCGCCACCAATTTCAGCCTGCTGAAACAGGCTGGCGACGTGG AAGAGAATCCCGGACCTATGGCACTGCCCGTCACTGCCTTGTTGCTGCCACTTGCACTGCTGCTCCAT GCCGCCAGGCCAGGCAAGCCCATTCCTAATCCTCTGCTGGGCCTCGATAGCACCGAACAGCTGGAAAA GAAGCTTCAGGCCCTCGAGAAGAAGCTGGCTCAGCTCGAATGGAAGAACCAGGCTCTCGAAAAGAAAC TCGCCCAAGGCAGTGGCGGCTCTGGAAGAGGACTGGATTTCGCCTGCGACTTCTGGGTGCTCGTGGTT GTCGGCGGAGTGCTGGCCTGTTATAGCCTGCTGGTCACAGTGGCCTTCATCATCTTTTGGGTCATGGCAttorney Docket No. 44807-0518WO1 / P18835-01TGCTGGCGGACCTGGTGCTGGATCTGCTGCACCTGTGTCCAGCACATCTAGCCTGCCACTGGCCGCTC TGAACATGAGAGTCAGAAGAAGGCTGAGCCTGTTCCTGAACGTGCGCACTCAGGTGGCCGCTGATTGG ACAGCTCTGGCCGAGGAAATGGACTTCGAGTACCTGGAAATCCGGCAGCTGGAAACACAGGCCGATCC TACAGGCAGACTGCTGGATGCTTGGCAAGGCAGACCTGGCGCTTCTGTGGGGAGACTGCTTGAGCTGC TGACAAAGCTGGGCAGAGATGACGTGCTGCTGGAACTGGGACCCAGCATCGAGGAAGATTGCCAGAAG TACATCCTGAAGCAGCAACAAGAGGAAGCCGAGAAGCCTCTGCAGGTTGCCGCCGTGGATAGCAGCGT TCCAAGAACAGCTGAGCTGGCCGGCATCACCACACTGGATGATCCTCTGGGAAAGAAGGTGGCCAAGA AGCCCACAAACAAGGCCCCTCATCCTAAGCAAGAGCCCCAAGAGATCAACTTCCCCGACGATCTGCCC GGCAGCAATACTGCAGCTCCCGTGCAAGAAACCCTGCACGGTTGTCAGCCCGTGACACAAGAGGACGG CAAAGAAAGCCGGATCAGCGTGCAAGAGAGACAGAGAGTGAAGTTCTCCAGAAGCGCTGACGCCCCAG CCTACCAACAGGGACAGAATCAACTCTACAATGAACTCAACCTCGGCAGGCGCGAGGAATATGATGTG CTGGATAAGAGGCGCGGCAGGGACCCAGAAATGGGAGGAAAACCTCAGCGGCGGAAAAACCCACAAGA GGGACTCTATAACGAACTCCAAAAGGATAAGATGGCAGAAGCCTATTCCGAGATTGGCATGAAGGGCG AACGTCGGAGAGGCAAAGGCCATGACGGACTCTATCAGGGACTGTCCACTGCCACAAAGGACACATAC GACGCACTCCATATGCAGGCACTCCCACCTAGACGGGCCAAACGATCTGGCTCTGGCCAGTGTACCAA CTATGCCCTGCTCAAGCTCGCTGGCGACGTCGAGTCTAACCCTGGACCAATGGGAGCTGGCGCTACAG GCAGAGCTATGGATGGACCTAGACTGCTGCTGCTCCTGCTTCTGGGAGTGTCTCTTGGCGGAGCCAAA GAGGCCTGTCCTACCGGCCTGTATACACACTCTGGCGAGTGCTGCAAGGCCTGCAATCTTGGAGAAGG CGTCGCACAGCCTTGCGGCGCTAATCAGACAGTGTGCGAGCCTTGCCTGGACAGCGTGACCTTTAGCG ACGTGGTGTCAGCCACCGAGCCATGCAAGCCATGTACCGAGTGTGTGGGCCTGCAGAGCATGTCTGCC CCTTGCGTGGAAGCTGACGATGCCGTGTGTAGATGCGCCTACGGCTACTACCAGGACGAGACAACAGG CAGATGCGAGGCCTGTAGAGTGTGCGAAGCTGGATCTGGCCTGGTGTTCAGCTGCCAAGACAAGCAGA ACACCGTGTGCGAGGAATGCCCCGATGGCACCTATAGCGACGAGGCCAACCATGTGGATCCCTGCCTG CCTTGTACCGTGTGTGAAGATACCGAGCGGCAGCTGCGCGAGTGTACAAGATGGGCTGATGCCGAGTG CGAAGAGATCCCTGGCAGATGGATCACCAGAAGCACACCTCCAGAGGGCAGCGATAGCACAGCCCCTT CTACACAAGAGCCCGAGGCTCCTCCTGAGCAGGACCTGATTGCTTCTACAGTGGCTGGCGTCGTGACC ACCGTGATGGGATCTAGTCAGCCCGTGGTCACCAGAGGCACCACCGACAATCTGATCCCCGTGTACTG TAGCATCCTGGCCGCCGTGGTTGTTGGACTGGTGGCCTATATCGCCTTCAAGCGGTGGAACAGCTGA(SEQ ID NO: 151)LINK CAR DesignCD8a SP - FLAG tag - H10-2-G3 - CD28 C141A Hinge - CD28 C165A TMD - LAT DeltaGADS -P2A - CD8a SP - myc tag - Cetux - CD8a Hinge - CD8a TMD - SLP-76 DeltaGADs - E2A - tNGFR Amino Acid Sequence for LINK CAR MALPVTALLLPLALLLHAARPDYKDDDDKDLGKKLLEAARAGQDDEVRILMANGADVNAKDEYGLTPL YLATAHGHLEIVEVLLKNGADVNAVDAIGFTPLHLAAFIGHLEI EVLLKHGADVNAQDKFGKTAFDI SIGNGNEDLAEILQKLNAAAIEVMYPPPYLDNEKSNGTIIHVKGKHLAPSPLFPGPSKPFWVLVVVGG VLAAYSLLVTVAFIIFWVGSHCHRLPGSYDSTSSDSLYPRGIQFKRPHTVAPWPPAYPPVTSYPPLSQ PDLLPIPRSPQPLGGSHRTPSSRRDSDGANSVASYENEGASGIRGAQAGWGVWGPSWTRLTPVSLPPE PACEDADEDEDDYHNPGYLVVLPDSTPATSTAAPSAPALSTPGIRDSAFSMESIDDRAKRSGSGATNF SLLKQAGDVEENPGPMALPVTALLLPLALLLHAARPEQKLISEEDLQVQLKQSGPGLVQPSQSLSITCAttorney Docket No. 44807-0518WO1 / P18835-01TVSGFSLTNYGVHWVRQSPGKGLEWLGVIWSGGNTDYNTPFTSRLSINKDNSKSQVFFKMNSLQSNDT AIYYCARALTYYDYEFAYWGQGTLVTVSAGGGGSGGGGSGGGGSDILLTQSPVILSVSPGERVSFSCR ASQSIGTNIHWYQQRTNGSPRLLIKYASESISGIPSRFSGSGSGTDFTLSINSVESEDIADYYCQQNN NWPTTFGAGTKLELKGLSTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWA PLAGTCGVLLLSLVITLYCKGSGSGSGALRNVPFRSEVLGWDPDSLADYFKKLNYKDCEKAVKKYHID GARFLNLTENDIQKFPKLRVPILSKLSQEINKNEERRSIFTRKPQVPRFPEETESHEEDNGGWSSFEE DDYESPNDDQDGEDDGDYESPNEEEEAPVEDDADYEPPPSNDEEALQNSILPAKPFPNSNSMYIDRPP SGKTPQQPPVPPQRPMAALPPPPAGRNHSPLPPPQTNHEEPSRSRRSLAPFDREPFTLGKKPPFSDKP SIPAGRSLGEHLPKIQKPPLPPTTERHERSSPLPGKKPPVPKHGWGPDRRENDEDDVHQRPLPQPALL PMSSNTFPSRSTKPSPMNPLPSSHMPGAFSESNSSFPQSASLPPYFSQGPSNRPPIRAEGRNFPLPLP NKPRPPSPAEEENSLNEEWYVSYITRPEAEAALRKINQDGTFLVRDSSKKTTTNPYVLMVLYKDKVYN IQIRYQKESQVYLLGTGLRGKEDFLSVSDI IDYFRKMPLLLIDGKNRGSRYQCTLTHAAGYPGNSRAK RSGSGQCTNYALLKLAGDVESNPGPMGAGATGRAMDGPRLLLLLLLGVSLGGAKEACPTGLYTHSGEC CKACNLGEGVAQPCGANQTVCEPCLDSVTFSDVVSATEPCKPCTECVGLQSMSAPCVEADDAVCRCAY GYYQDETTGRCEACRVCEAGSGLVFSCQDKQNTVCEECPDGTYSDEANHVDPCLPCTVCEDTERQLRE CTRWADAECEEIPGRWITRSTPPEGSDSTAPSTQEPEAPPEQDLIASTVAGVVTTVMGSSQPVVTRGT TDNLIPVYCSILAAVVVGLVAYIAFKRWNS (SEQ ID NO: 152)Nucleic Acid Sequence for LINK CAR ATGGCTCTGCCTGTGACAGCTCTGCTGCTGCCTCTGGCTCTGCTTCTGCATGCTGCTAGACCTGACTA CAAGGACGACGACGACAAGGATCTGGGAAAGAAGCTGCTGGAAGCCGCCAGAGCCGGACAGGATGATG AAGTGCGGATCCTGATGGCCAACGGCGCCGATGTGAATGCCAAGGACGAGTACGGACTGACCCCTCTG TATCTGGCCACAGCTCACGGCCACCTGGAAATTGTGGAAGTGCTGCTGAAGAATGGGGCCGACGTGAA CGCCGTGGATGCCATCGGTTTTACCCCTCTGCACCTGGCTGCCTTCATCGGCCATCTCGAAATTGCCG AGGTCCTGCTGAAGCACGGCGCTGATGTTAACGCCCAGGATAAGTTCGGCAAGACCGCCTTCGACATC AGCATCGGCAACGGCAACGAAGATCTGGCCGAGATCCTGCAGAAACTGAACGCCGCCGCTATCGAAGT GATGTACCCTCCACCTTACCTGGACAATGAGAAGTCCAACGGCACCATCATCCACGTGAAGGGCAAGC ACCTGGCTCCATCTCCACTGTTCCCTGGACCTAGCAAGCCCTTCTGGGTGCTCGTTGTTGTTGGCGGA GTGCTGGCCGCCTATAGCCTGCTGGTTACCGTGGCCTTCATCATCTTTTGGGTGGGAAGCCACTGCCA CAGACTGCCCGGCAGCTACGATAGCACCAGCAGCGATTCTCTGTACCCCAGAGGCATCCAGTTCAAGC GGCCTCATACAGTGGCTCCCTGGCCTCCTGCTTACCCTCCTGTGACAAGCTACCCTCCACTGAGCCAG CCTGACCTGCTGCCTATTCCTAGAAGCCCTCAGCCTCTCGGCGGCAGCCATAGAACACCTAGCAGCAG AAGAGATAGCGACGGCGCCAATAGCGTGGCCAGCTACGAAAATGAAGGCGCCTCTGGCATTAGAGGCG CCCAAGCTGGATGGGGAGTTTGGGGACCTAGCTGGACAAGACTGACCCCTGTGTCTCTGCCTCCTGAA CCTGCCTGCGAAGATGCCGACGAGGACGAGGATGACTATCACAACCCTGGCTACCTGGTGGTGCTGCC TGATAGCACACCAGCCACATCTACAGCCGCTCCTAGTGCTCCTGCTCTGAGCACACCTGGCATCAGAG ACAGCGCCTTCAGCATGGAATCCATCGACGACAGAGCCAAGAGAAGCGGCAGCGGCGCCACCAATTTC AGCCTGCTTAAACAGGCCGGCGACGTGGAAGAGAACCCCGGACCTATGGCACTGCCAGTTACTGCCCT TCTGCTCCCACTGGCACTGCTGCTTCACGCCGCCAGACCTGAGCAGAAGCTGATCTCCGAAGAGGACC TGCAAGTGCAGCTGAAGCAGTCTGGACCTGGACTGGTGCAGCCTAGCCAGAGCCTGAGCATCACCTGTAttorney Docket No. 44807-0518WO1 / P18835-01ACCGTGTCCGGCTTCAGCCTGACCAATTACGGCGTGCACTGGGTCCGACAGAGCCCTGGAAAAGGACT GGAATGGCTGGGAGTGATTTGGAGCGGCGGCAACACCGACTACAACACCCCATTCACCAGCAGACTGT CCATCAACAAGGACAACAGCAAGAGCCAGGTGTTCTTCAAGATGAACAGCCTGCAGAGCAACGACACC GCCATCTACTACTGCGCTAGAGCCCTGACCTACTACGACTACGAGTTCGCCTATTGGGGCCAGGGCAC ACTGGTTACAGTTTCTGCTGGCGGCGGAGGATCTGGCGGAGGTGGAAGCGGAGGCGGTGGATCTGATA TCCTGCTGACACAGAGCCCCGTGATCCTGTCTGTGTCTCCTGGCGAGAGAGTGTCCTTCAGCTGTAGA GCCAGCCAGTCCATCGGCACCAACATCCACTGGTATCAGCAGCGGACCAACGGCAGCCCTCGGCTGCT GATTAAGTACGCCAGCGAGAGCATCAGCGGCATCCCCAGCAGATTTTCTGGCAGCGGCTCTGGCACCG ACTTCACCCTGTCTATCAACAGCGTGGAAAGCGAGGATATCGCCGATTACTACTGTCAGCAGAACAAC AACTGGCCCACCACCTTTGGAGCCGGCACCAAGCTGGAACTGAAGGGCCTGAGCACAACAACCCCTGC TCCTAGACCTCCTACACCAGCTCCTACAATCGCCAGCCAGCCTCTGTCTCTGAGGCCAGAGGCTTGTA GACCTGCTGCTGGCGGAGCCGTGCATACAAGAGGACTGGATTTCGCCTGCGATATCTATATCTGGGCT CCTCTGGCCGGCACCTGTGGTGTTCTGCTGCTGTCTCTGGTCATCACCCTGTACTGTAAGGGATCTGG ATCAGGCAGCGGAGCCCTGCGGAACGTGCCCTTCAGATCCGAAGTGCTCGGCTGGGATCCTGACAGCC TGGCCGACTACTTCAAGAAGCTGAATTACAAGGACTGCGAGAAGGCCGTGAAGAAGTACCATATCGAC GGGGCCAGATTCCTGAATCTGACCGAGAACGATATCCAGAAGTTCCCTAAGCTGCGGGTGCCCATCCT GAGCAAGCTGTCCCAAGAGATCAACAAGAACGAGGAACGGCGGAGCATCTTCACCCGGAAACCTCAGG TGCCCAGATTTCCCGAGGAAACCGAGAGCCACGAAGAGGACAATGGCGGCTGGTCCAGCTTCGAGGAA GATGATTACGAGAGCCCTAACGACGACCAGGACGGCGAGGATGATGGCGATTACGAGTCTCCCAATGA AGAGGAAGAGGCCCCTGTCGAGGACGACGCCGATTATGAACCTCCTCCTAGCAACGACGAAGAAGCCC TGCAGAACAGCATCCTGCCTGCCAAGCCTTTTCCAAACAGCAACAGCATGTACATCGACCGGCCTCCA TCCGGCAAGACACCTCAGCAACCTCCAGTTCCTCCACAGAGGCCAATGGCTGCTTTGCCTCCTCCACC AGCCGGCAGAAATCACTCTCCATTGCCTCCACCTCAGACCAACCACGAGGAACCCAGCCGGTCCAGAA GATCTCTGGCCCCTTTCGACAGAGAGCCCTTCACACTGGGCAAGAAGCCTCCATTCAGCGACAAGCCT AGCATCCCTGCCGGAAGAAGCCTGGGAGAGCATCTGCCCAAGATCCAGAAGCCACCTCTGCCACCTAC CACAGAGAGACACGAGAGAAGCAGCCCTCTGCCTGGCAAAAAGCCACCAGTGCCTAAGCACGGCTGGG GCCCTGATAGAAGAGAGAATGACGAAGATGATGTGCACCAGCGGCCTCTGCCTCAACCTGCACTGCTT CCCATGAGCAGCAACACATTCCCCAGCAGAAGCACCAAGCCTAGTCCTATGAATCCCCTGCCTAGCAG CCATATGCCAGGCGCCTTTAGCGAGAGCAACTCCAGCTTTCCTCAGAGCGCTAGCCTGCCTCCTTACT TCAGCCAGGGGCCTAGCAACCGGCCACCTATTAGAGCCGAAGGCCGGAACTTTCCCCTGCCACTGCCT AACAAGCCCAGACCACCATCTCCAGCCGAAGAAGAGAACTCCCTGAACGAAGAGTGGTACGTGTCCTA CATCACCCGGCCTGAAGCCGAAGCTGCCCTGAGAAAGATCAACCAGGATGGCACCTTCCTCGTGCGGG ACAGCTCCAAGAAAACCACCACAAATCCCTACGTGCTGATGGTGCTGTACAAGGACAAGGTCTACAAT ATCCAGATCCGGTATCAGAAAGAGAGCCAGGTCTACCTGCTCGGCACAGGCCTGAGAGGAAAAGAGGA TTTCCTGAGCGTCAGCGACATCATCGACTACTTTAGAAAGATGCCCCTGCTCCTGATCGACGGCAAGA ACAGGGGCTCCAGATACCAGTGCACTCTGACACACGCTGCCGGCTATCCTGGCAATTCCCGGGCCAAA CGATCTGGCTCTGGCCAGTGTACCAACTATGCCCTGCTCAAGCTCGCTGGCGACGTCGAGTCTAACCC TGGACCAATGGGAGCTGGCGCTACAGGCAGAGCTATGGATGGACCTAGACTGCTGCTGCTCCTGCTTC TGGGAGTGTCTCTTGGCGGAGCCAAAGAGGCCTGTCCTACCGGCCTGTATACACACTCTGGCGAGTGC TGCAAGGCCTGCAATCTTGGAGAAGGCGTCGCACAGCCTTGCGGCGCTAATCAGACAGTGTGCGAGCC TTGCCTGGACAGCGTGACCTTTAGCGACGTGGTGTCAGCCACCGAGCCATGCAAGCCATGTACCGAGT GTGTGGGCCTGCAGAGCATGTCTGCCCCTTGCGTGGAAGCTGACGATGCCGTGTGTAGATGCGCCTAC GGCTACTACCAGGACGAGACAACAGGCAGATGCGAGGCCTGTAGAGTGTGCGAAGCTGGATCTGGCCT GGTGTTCAGCTGCCAAGACAAGCAGAACACCGTGTGCGAGGAATGCCCCGATGGCACCTATAGCGACG AGGCCAACCATGTGGATCCCTGCCTGCCTTGTACCGTGTGTGAAGATACCGAGCGGCAGCTGCGCGAG TGTACAAGATGGGCTGATGCCGAGTGCGAAGAGATCCCTGGCAGATGGATCACCAGAAGCACACCTCC AGAGGGCAGCGATAGCACAGCCCCTTCTACACAAGAGCCCGAGGCTCCTCCTGAGCAGGACCTGATTG CTTCTACAGTGGCTGGCGTCGTGACCACCGTGATGGGATCTAGTCAGCCCGTGGTCACCAGAGGCACCAttorney Docket No. 44807-0518WO1 / P18835-01ACCGACAATCTGATCCCCGTGTACTGTAGCATCCTGGCCGCCGTGGTTGTTGGACTGGTGGCCTATAT CGCCTTCAAGCGGTGGAACAGCTGA(SEQ ID NO: 153)Example 5: Exemplary MANTIS SequencesThis Example provides sequences of exemplary MANTIS molecules.MANTIS-1 DesignCD8a SP - myc tag - BB7.2 - CD45 ECD - NOTCH1 TMD - NOTCH2 JMD - Linker 2 - CD3z Signaling - 41BB CoStim - G4S - TM1 ID JMD - TM1 ID TMD - G4Sx3 - FMC63 - FLAG tag - E2A - tNGFRAmino Acid Sequence for MANTIS- 1 MALPVTALLLPLALLLHAARPEQKLISEEDLQVQLQQSGPELVKPGASVKMSCKASGYTFTSYHIQWV KQRPGQGLEWIGWIYPGDGSTQYNEKFKGKTTLTADKSSSTAYMLLSSLTSEDSAIYFCAREGTYYAM DYWGQGTSVTVSSGGGGSGGGGSGGGGSDIVMTQAPLSLPVSLGDQVSISCRSSQSIVHSNGNTYLEW YLQKPGQSPKLLIYKVSNRFSGVPDRFSGSGSGTDFTLKISRVEAEDLGVYYCFQGSHVPRT FGGGTK LELKRTQSPTPSPTGLTTAKMPSVPLSSDPLPTHTTAFSPASTFERENDFSETTTSLSPDNTSTQVSP DSLDNASAFNTTGVSSVQTPHLPTHADSQTPSAGTDTQTFSGSAANAKLNPTPGSNAISDVPGERSTA STFPTDPVSPLTTTLSLAHHSSAALPARTSNTTITANTSDAYLNASETTTLSPSGSAVISTTTIATTP SKPTCDEKYANITVDYLYNKETKLFTAKLNVNENVECGNNTCTNNEVHNLTECKNASVSISHNSCTAP DKTLILDVPPGVEKFQLHDCTQVEKADTTICLKWKNIETFTCDTQNITYRFQCGNMIFDNKEIKLENL EPEHEYKCDSEILYNNHKFTNASKIIKTDFGSPGEPQIIFCRSEAAHQGVITWNPPQRSFHNFTLCYI KETEKDCLNLDKNLIKYDLQNLKPYTKYVLSLHAYIIAKVQRNGSAAMCHFTTKSAPPSQVWNMTVSM TSDNSMHVKCRPPRDRNGPHERYHLEVEAGNTLVRNESHKNCDFRVKDLQYSTDYTFKAYFHNGDYPG EPFILHHSTSYNSKFMYVAAAAFVLLFFVGCGVLLSKRKRKHGSGSGSGSSLRVKFSRSADAPAYQQG QNQLYNELNLGRREEYDVLDKRRGRDPEMGGKPQRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRG KGHDGLYQGLSTATKDTYDALHMQALPPRKRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGG CELGGGGSYRPARVTSTSRFLNPYVVCFIVVAGVVILAVTIALLVY FLAFDQKSYFSTLEISGGGGGS GGGGSGGGGSDIQMTQTTSSLSASLGDRVTISCRASQDISKYLNWYQQKPDGTVKLLIYHTSRLHSGV PSRFSGSGSGTDYSLTISNLEQEDIATYFCQQGNTLPYTFGGGTKLEITGSTSGSGKPGSGEGSTKGE VKLQESGPGLVAPSQSLSVTCTVSGVSLPDYGVSWIRQPPRKGLEWLGVIWGSETTYYNSALKSRLTI IKDNSKSQVFLKMNSLQTDDTAIYYCAKHYYYGGSYAMDYWGQGTSVTVSSAAADYKDDDDKRAKRSG SGQCTNYALLKLAGDVESNPGPMGAGATGRAMDGPRLLLLLLLGVSLGGAKEACPTGLYTHSGECCKA CNLGEGVAQPCGANQTVCEPCLDSVTFSDVVSATEPCKPCTECVGLQSMSAPCVEADDAVCRCAYGYY QDETTGRCEACRVCEAGSGLVFSCQDKQNTVCEECPDGTYSDEANHVDPCLPCTVCEDTERQLRECTR WADAECEEIPGRWITRSTPPEGSDSTAPSTQEPEAPPEQDLIASTVAGVVTTVMGSSQPVVTRGTTDNNucleic Acid Sequence for MANTIS-1 ATGGCTCTGCCTGTGACAGCTCTGCTGCTGCCTCTGGCTCTGCTTCTGCATGCCGCTAGACCTGAGCA GAAGCTGATCTCCGAAGAGGACCTGCAGGTTCAGCTGCAGCAGTCTGGACCTGAGCTGGTTAAGCCTG GCGCTTCCGTGAAGATGAGCTGCAAGGCCAGCGGCTACACCTTCACCAGCTACCACATCCAGTGGGTCAttorney Docket No. 44807-0518WO1 / P18835-01AAGCAGAGGCCTGGACAGGGACTCGAGTGGATCGGCTGGATCTATCCTGGCGACGGCAGCACCCAGTA CAACGAGAAGTTCAAGGGCAAGACCACACTGACCGCCGACAAGAGCAGCAGCACAGCCTACATGCTGC TGAGCAGCCTGACCAGCGAGGACAGCGCCATCTACTTTTGTGCCAGAGAGGGCACCTACTACGCCATG GATTATTGGGGCCAGGGCACCAGCGTGACAGTCTCTTCTGGTGGCGGAGGATCTGGCGGAGGTGGAAG CGGCGGAGGCGGATCTGATATCGTGATGACACAGGCCCCTCTGAGCCTGCCTGTGTCTCTGGGAGATC AGGTGTCCATCAGCTGTCGGAGCAGCCAGAGCATCGTGCACAGCAACGGCAACACCTACCTGGAATGG TATCTGCAGAAGCCCGGACAGAGCCCCAAGCTGCTGATCTACAAGGTGTCCAACCGGTTCAGCGGCGT GCCCGATAGATTTTCTGGCTCTGGCAGCGGCACCGACTTCACCCTGAAGATCTCTAGAGTGGAAGCCG AGGACCTGGGCGTGTACTACTGCTTCCAAGGCAGCCACGTGCCAAGAACCTTTGGCGGCGGAACAAAG CTGGAACTGAAGCGGACACAGAGCCCCACACCATCTCCAACAGGACTGACCACCGCCAAGATGCCTAG CGTGCCCCTCTCTTCTGACCCTCTGCCTACACACACCACCGCTTTTAGCCCTGCCAGCACCTTCGAGA GAGAGAACGACTTCAGCGAGACAACCACCTCTCTGAGCCCCGACAACACCAGCACACAGGTGTCCCCA GACAGCCTGGATAATGCCAGCGCCTTCAATACCACCGGCGTGTCCTCTGTGCAGACCCCTCATCTGCC AACACACGCCGATAGCCAGACACCTTCTGCCGGCACCGATACACAGACCTTTTCTGGCTCTGCCGCCA ACGCCAAGCTGAACCCTACACCTGGCAGCAACGCCATCTCTGATGTGCCTGGCGAGAGAAGCACCGCC AGCACATTTCCAACAGACCCCGTGTCTCCCCTGACCACCACACTGTCTCTGGCCCACCATAGCTCTGC TGCCCTGCCTGCCAGAACCAGCAACACCACCATCACCGCCAATACCAGCGACGCCTACCTGAACGCCA GCGAAACCACAACACTGAGCCCTAGCGGAAGCGCCGTGATCAGCACAACCACAATCGCCACCACACCT AGCAAGCCTACCTGCGACGAGAAGTACGCCAACATCACCGTGGACTACCTGTACAACAAAGAGACAAA GCTGTTCACGGCCAAGCTCAACGTGAACGAGAACGTGGAATGCGGCAACAATACCTGCACCAACAACG AGGTGCACAACCTGACCGAGTGCAAGAACGCCTCCGTGTCCATCAGCCACAACAGCTGCACAGCCCCT GACAAGACCCTGATCCTGGATGTGCCTCCTGGCGTGGAAAAGTTCCAGCTGCACGATTGCACCCAGGT GGAAAAGGCCGATACCACCATCTGCCTGAAGTGGAAGAACATCGAGACATTCACCTGTGACACCCAGA ACATCACCTACCGGTTCCAGTGCGGCAATATGATCTTCGATAACAAAGAAATCAAGCTCGAGAACCTC GAGCCTGAGCACGAGTACAAGTGCGACAGCGAGATCCTGTATAACAATCACAAGTTCACCAACGCCAG CAAGATCATCAAGACCGACTTCGGCTCTCCCGGCGAGCCCCAGATCATCTTCTGTAGATCTGAGGCCG CTCACCAGGGCGTGATCACCTGGAATCCTCCACAGCGGAGCTTCCACAACTTCACCCTGTGCTACATC AAAGAAACCGAGAAGGACTGCCTGAACCTGGACAAGAACCTCATTAAGTACGACCTGCAGAACCTGAA GCCGTACACCAAATACGTGCTGAGCCTGCACGCCTACATCATTGCCAAGGTGCAGAGAAATGGCAGCG CCGCCATGTGCCACTTCACCACAAAAAGCGCCCCTCCAAGCCAAGTGTGGAACATGACCGTGTCTATG ACCAGCGACAACTCCATGCACGTGAAGTGCCGGCCTCCACGGGATAGAAATGGCCCTCACGAGAGATA CCACCTGGAAGTCGAGGCCGGAAATACCCTCGTGCGGAACGAGAGCCACAAGAACTGCGACTTCAGAG TGAAGGACCTGCAGTACAGCACCGACTACACCTTCAAGGCCTACTTCCACAATGGCGACTACCCTGGC GAGCCCTTCATCCTGCACCACAGCACCAGCTACAACAGCAAGTTTATGTACGTGGCCGCTGCTGCCTT CGTGCTGCTGTTCTTTGTTGGCTGCGGAGTGCTGCTGAGCAAGCGGAAGAGAAAGCACGGATCTGGAT CAGGCAGCGGAAGCTCTCTGCGCGTGAAGTTCAGCAGATCAGCCGACGCTCCTGCCTATCAGCAGGGC CAGAACCAGCTGTACAACGAGCTGAACCTGGGGAGAAGAGAAGAGTACGACGTGCTGGACAAGCGGAG AGGCAGAGATCCTGAGATGGGCGGAAAGCCCCAGCGGAGAAAGAATCCTCAAGAGGGCCTGTATAATG AGCTGCAGAAAGACAAGATGGCCGAGGCCTACAGCGAGATCGGAATGAAGGGCGAGCGCAGAAGAGGC AAGGGACACGATGGACTGTACCAGGGCCTGAGCACCGCCACCAAGGATACCTATGATGCCCTGCACAT GCAGGCCCTGCCTCCAAGAAAGCGGGGCAGAAAGAAGCTGCTGTACATCTTCAAGCAGCCCTTCATGC GGCCCGTGCAGACCACACAAGAGGAAGATGGCTGCTCCTGCAGATTCCCCGAGGAAGAAGAAGGCGGC TGCGAACTTGGAGGCGGCGGATCTTATAGACCCGCCAGAGTGACCAGCACCAGCCGGTTTCTGAACCC CTACGTCGTGTGCTTCATTGTGGTGGCCGGCGTTGTGATCCTGGCCGTGACAATTGCCCTGCTGGTGT ACTTCCTGGCCTTCGACCAGAAGTCCTACTTCAGCACCCTGGAAATCTCTGGCGGAGGCGGAGGATCT GGTGGCGGAGGAAGCGGTGGCGGCGGTTCTGACATCCAGATGACCCAGACCACAAGCAGCCTGTCTGC CAGCCTGGGCGATAGAGTGACCATCAGCTGTAGAGCCAGCCAGGACATCAGCAAGTACCTGAACTGGT ATCAGCAAAAGCCCGACGGCACCGTGAAGCTGCTGATCTACCACACCAGCAGACTGCACAGCGGCGTG CCAAGCAGATTTTCTGGCAGCGGCTCTGGCACCGACTACAGCCTGACAATCAGCAACCTGGAACAAGAAttorney Docket No. 44807-0518WO1 / P18835-01GGATATCGCTACCTACTTCTGCCAGCAAGGCAACACCCTGCCTTACACCTTTGGCGGAGGCACCAAGC TGGAAATCACCGGCTCTACAAGCGGCAGCGGCAAACCTGGATCTGGCGAGGGATCTACCAAGGGCGAA GTGAAACTGCAAGAGTCTGGCCCTGGACTGGTGGCCCCATCTCAGTCTCTGAGCGTGACCTGTACAGT CAGCGGAGTGTCCCTGCCTGATTACGGCGTGTCCTGGATCAGACAGCCTCCTCGGAAAGGCCTGGAAT GGCTGGGAGTGATCTGGGGCAGCGAGACAACCTACTACAACAGCGCCCTGAAGTCCCGGCTGACCATC ATCAAGGACAACTCCAAGAGCCAGGTGTTCCTGAAGATGAACAGCCTGCAGACCGACGACACCGCCAT CTACTATTGCGCCAAGCACTACTACTACGGCGGCAGCTACGCCATGGATTATTGGGGCCAGGGCACCA GCGTGACCGTTTCTTCTGCCGCCGCTGACTACAAGGACGACGACGACAAGCGGGCCAAACGATCTGGC TCTGGCCAGTGTACCAACTATGCCCTGCTCAAGCTCGCTGGCGACGTCGAGTCTAACCCTGGACCAAT GGGAGCTGGCGCTACAGGCAGAGCTATGGATGGACCTAGACTGCTGCTGCTCCTGCTTCTGGGAGTGT CTCTTGGCGGAGCCAAAGAGGCCTGTCCTACCGGCCTGTATACACACTCTGGCGAGTGCTGCAAGGCC TGCAATCTTGGAGAAGGCGTCGCACAGCCTTGCGGCGCTAATCAGACAGTGTGCGAGCCTTGCCTGGA CAGCGTGACCTTTAGCGACGTGGTGTCAGCCACCGAGCCATGCAAGCCATGTACCGAGTGTGTGGGCC TGCAGAGCATGTCTGCCCCTTGCGTGGAAGCTGACGATGCCGTGTGTAGATGCGCCTACGGCTACTAC CAGGACGAGACAACAGGCAGATGCGAGGCCTGTAGAGTGTGCGAAGCTGGATCTGGCCTGGTGTTCAG CTGCCAAGACAAGCAGAACACCGTGTGCGAGGAATGCCCCGATGGCACCTATAGCGACGAGGCCAACC ATGTGGATCCCTGCCTGCCTTGTACCGTGTGTGAAGATACCGAGCGGCAGCTGCGCGAGTGTACAAGA TGGGCTGATGCCGAGTGCGAAGAGATCCCTGGCAGATGGATCACCAGAAGCACACCTCCAGAGGGCAG CGATAGCACAGCCCCTTCTACACAAGAGCCCGAGGCTCCTCCTGAGCAGGACCTGATTGCTTCTACAG TGGCTGGCGTCGTGACCACCGTGATGGGATCTAGTCAGCCCGTGGTCACCAGAGGCACCACCGACAAT CTGATCCCCGTGTACTGTAGCATCCTGGCCGCCGTGGTTGTTGGACTGGTGGCCTATATCGCCTTCAA GCGGTGGAACAGCTGA(SEQ ID NO: 120)MANTIS-2 DesignCD8a SP - myc tag - BB7.2 - CD45 ECD - human NOTCH1 NRR - NOTCH1 TMD - NOTCH2 JMD - Linker 2 - CD3z Signaling - 41BB CoStim - G4S - TM1 ID JMD - TM1 ID TMD - G4Sx3 -FMC63 - FLAG tag - E2A - tNGFRAmino Acid Sequence for MANTIS-2 MALPVTALLLPLALLLHAARPEQKLISEEDLQVQLQQSGPELVKPGASVKMSCKASGYTFTSYHIQWV KQRPGQGLEWIGWIYPGDGSTQYNEKFKGKTTLTADKSSSTAYMLLSSLTSEDSAIYFCAREGTYYAM DYWGQGTSVTVSSGGGGSGGGGSGGGGSDIVMTQAPLSLPVSLGDQVSISCRSSQSIVHSNGNTYLEW YLQKPGQSPKLLIYKVSNRFSGVPDRFSGSGSGTDFTLKISRVEAEDLGVYYCFQGSHVPRT FGGGTK LELKRTQSPTPSPTGLTTAKMPSVPLSSDPLPTHTTAFSPASTFERENDFSETTTSLSPDNTSTQVSP DSLDNASAFNTTGVSSVQTPHLPTHADSQTPSAGTDTQTFSGSAANAKLNPTPGSNAISDVPGERSTA STFPTDPVSPLTTTLSLAHHSSAALPARTSNTTITANTSDAYLNASETTTLSPSGSAVISTTTIATTP SKPTCDEKYANITVDYLYNKETKLFTAKLNVNENVECGNNTCTNNEVHNLTECKNASVSISHNSCTAP DKTLILDVPPGVEKFQLHDCTQVEKADTTICLKWKNIETFTCDTQNITYRFQCGNMIFDNKEIKLENL EPEHEYKCDSEILYNNHKFTNASKIIKTDFGSPGEPQIIFCRSEAAHQGVITWNPPQRSFHNFTLCYI KETEKDCLNLDKNLIKYDLQNLKPYTKYVLSLHAYIIAKVQRNGSAAMCHFTTKSAPPSQVWNMTVSM TSDNSMHVKCRPPRDRNGPHERYHLEVEAGNTLVRNESHKNCDFRVKDLQYSTDYTFKAYFHNGDYPG EPFILHHSTSYNSKILDYSFGGGAGRDIPPPLIEEACELPECQEDAGNKVCSLQCNNHACGWDGGDCS LNFNDPWKNCTQSLQCWKYFSDGHCDSQCNSAGCLFDGFDCQRAEGQCNPLYDQYCKDHFSDGHCDQG CNSAECEWDGLDCAEHVPERLAAGTLVVVVLMPPEQLRNSSFHFLRELSRVLHTNVVFKRDAHGQQMI FPYYGREEELRKHPIKRAAEGWAAPDALLGQVKASLLPGGSEGGRRRRELDPMDVRGSIVYLEIDNRQ CVQASSQCFQSATDVAAFLGALASLGSLNIPYKIEAVQSETVEPPPPAQLHFMYVAAAAFVLLFFVGCAttorney Docket No. 44807-0518WO1 / P18835-01GVLLSKRKRKHGSGSGSGSSLRVKFSRSADAPAYQQGQNQLYNELNLGRREEYDVLDKRRGRDPEMGG KPQRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPRKR GRKKLLYI FKQPFMRPVQTTQEEDGCSCRFPEEEEGGCELGGGGSYRPARVTSTSRFLNPYVVCFIVV AGVVILAVTIALLVYFLAFDQKSYFSTLEISGGGGGSGGGGSGGGGSDIQMTQTTSSLSASLGDRVTI SCRASQDISKYLNWYQQKPDGTVKLLIYHTSRLHSGVPSRFSGSGSGTDYSLTISNLEQEDIATYFCQ QGNTLPYTFGGGTKLEITGSTSGSGKPGSGEGSTKGEVKLQESGPGLVAPSQSLSVTCTVSGVSLPDY GVSWIRQPPRKGLEWLGVIWGSETTYYNSALKSRLTIIKDNSKSQVFLKMNSLQTDDTAIYYCAKHYY YGGSYAMDYWGQGTSVTVSSAAADYKDDDDKRAKRSGSGQCTNYALLKLAGDVESNPGPMGAGATGRA MDGPRLLLLLLLGVSLGGAKEACPTGLYTHSGECCKACNLGEGVAQPCGANQTVCEPCLDSVTFSDVV SATEPCKPCTECVGLQSMSAPCVEADDAVCRCAYGYYQDETTGRCEACRVCEAGSGLVFSCQDKQNTV CEECPDGTYSDEANHVDPCLPCTVCEDTERQLRECTRWADAECEEIPGRWITRSTPPEGSDSTAPSTQ EPEAPPEQDLIASTVAGVVTTVMGSSQPVVTRGTTDNLIPVYCSILAAVVVGLVAYIAFKRWNS* (SEQ ID NO:5)Nucleic Acid Sequence for MANTIS-2 ATGGCTCTGCCTGTGACAGCTCTGCTGCTGCCTCTGGCTCTGCTTCTGCATGCCGCTAGACCTGAGCA GAAGCTGATCTCCGAAGAGGACCTGCAGGTTCAGCTGCAGCAGTCTGGACCTGAGCTGGTTAAGCCTG GCGCTTCCGTGAAGATGAGCTGCAAGGCCAGCGGCTACACCTTCACCAGCTACCACATCCAGTGGGTC AAGCAGAGGCCTGGACAGGGACTCGAGTGGATCGGCTGGATCTATCCTGGCGACGGCAGCACCCAGTA CAACGAGAAGTTCAAGGGCAAGACCACACTGACCGCCGACAAGAGCAGCAGCACAGCCTACATGCTGC TGAGCAGCCTGACCAGCGAGGACAGCGCCATCTACTTTTGTGCCAGAGAGGGCACCTACTACGCCATG GATTATTGGGGCCAGGGCACCAGCGTGACAGTCTCTTCTGGTGGCGGAGGATCTGGCGGAGGTGGAAG CGGCGGAGGCGGATCTGATATCGTGATGACACAGGCCCCTCTGAGCCTGCCTGTGTCTCTGGGAGATC AGGTGTCCATCAGCTGTCGGAGCAGCCAGAGCATCGTGCACAGCAACGGCAACACCTACCTGGAATGG TATCTGCAGAAGCCCGGACAGAGCCCCAAGCTGCTGATCTACAAGGTGTCCAACCGGTTCAGCGGCGT GCCCGATAGATTTTCTGGCTCTGGCAGCGGCACCGACTTCACCCTGAAGATCTCTAGAGTGGAAGCCG AGGACCTGGGCGTGTACTACTGCTTCCAAGGCAGCCACGTGCCAAGAACCTTTGGCGGCGGAACAAAG CTGGAACTGAAGCGGACACAGAGCCCCACACCATCTCCAACAGGACTGACCACCGCCAAGATGCCTAG CGTGCCCCTCTCTTCTGACCCTCTGCCTACACACACCACCGCTTTTAGCCCTGCCAGCACCTTCGAGA GAGAGAACGACTTCAGCGAGACAACCACCTCTCTGAGCCCCGACAACACCAGCACACAGGTGTCCCCA GACAGCCTGGATAATGCCAGCGCCTTCAATACCACCGGCGTGTCCTCTGTGCAGACCCCTCATCTGCC AACACACGCCGATAGCCAGACACCTTCTGCCGGCACCGATACACAGACCTTTTCTGGCTCTGCCGCCA ACGCCAAGCTGAACCCTACACCTGGCAGCAACGCCATCTCTGATGTGCCTGGCGAGAGAAGCACCGCC AGCACATTTCCAACAGACCCCGTGTCTCCCCTGACCACCACACTGTCTCTGGCCCACCATAGCTCTGC TGCCCTGCCTGCCAGAACCAGCAACACCACCATCACCGCCAATACCAGCGACGCCTACCTGAACGCCA GCGAAACCACAACACTGAGCCCTAGCGGAAGCGCCGTGATCAGCACAACCACAATCGCCACCACACCT AGCAAGCCTACCTGCGACGAGAAGTACGCCAACATCACCGTGGACTACCTGTACAACAAAGAGACAAA GCTGTTCACGGCCAAGCTCAACGTGAACGAGAACGTGGAATGCGGCAACAATACCTGCACCAACAACG AGGTGCACAACCTGACCGAGTGCAAGAACGCCTCCGTGTCCATCAGCCACAACAGCTGCACAGCCCCT GACAAGACCCTGATCCTGGATGTGCCTCCTGGCGTGGAAAAGTTCCAGCTGCACGATTGCACCCAGGT GGAAAAGGCCGATACCACCATCTGCCTGAAGTGGAAGAACATCGAGACATTCACCTGTGACACCCAGA ACATCACCTACCGGTTCCAGTGCGGCAATATGATCTTCGATAACAAAGAAATCAAGCTCGAGAACCTC GAGCCTGAGCACGAGTACAAGTGCGACAGCGAGATCCTGTATAACAATCACAAGTTCACCAACGCCAG CAAGATCATCAAGACCGACTTCGGCTCTCCCGGCGAGCCCCAGATCATCTTCTGTAGATCTGAGGCCG CTCACCAGGGCGTGATCACCTGGAATCCTCCACAGCGGAGCTTCCACAACTTCACCCTGTGCTACATC AAAGAAACCGAGAAGGACTGCCTGAACCTGGACAAGAACCTCATTAAGTACGACCTGCAGAACCTGAA GCCGTACACCAAATACGTGCTGAGCCTGCACGCCTACATCATTGCCAAGGTGCAGAGAAATGGCAGCG CCGCCATGTGCCACTTCACCACAAAAAGCGCCCCTCCAAGCCAAGTGTGGAACATGACCGTGTCTATGAttorney Docket No. 44807-0518WO1 / P18835-01ACCAGCGACAACTCCATGCACGTGAAGTGCCGGCCTCCACGGGATAGAAATGGCCCTCACGAGAGATA CCACCTGGAAGTCGAGGCCGGAAATACCCTCGTGCGGAACGAGAGCCACAAGAACTGCGACTTCAGAG TGAAGGACCTGCAGTACAGCACCGACTACACCTTCAAGGCCTACTTCCACAATGGCGACTACCCTGGC GAGCCCTTCATCCTGCACCACAGCACCAGCTACAACAGCAAGATCCTGGACTACAGCTTCGGCGGAGG CGCCGGAAGAGATATTCCTCCACCTCTGATCGAGGAAGCCTGCGAGCTGCCTGAGTGTCAAGAGGACG CCGGCAACAAAGTGTGCAGCCTGCAGTGCAACAATCACGCCTGTGGATGGGATGGCGGCGACTGCAGC CTGAACTTCAACGACCCCTGGAAGAACTGCACCCAGTCTCTGCAGTGCTGGAAGTACTTTAGCGACGG CCACTGCGACAGCCAGTGTAATTCTGCCGGCTGCCTGTTCGACGGCTTCGATTGTCAGCGAGCCGAGG GCCAATGCAACCCTCTGTACGACCAGTACTGCAAGGACCACTTCTCCGATGGCCACTGTGACCAGGGC TGTAATAGCGCCGAGTGCGAGTGGGATGGACTGGATTGTGCCGAGCACGTGCCAGAAAGACTGGCCGC TGGAACACTGGTGGTGGTCGTTCTGATGCCTCCTGAGCAGCTGCGGAACAGCAGCTTCCACTTCCTGC GGGAACTGAGCAGAGTGCTGCACACCAACGTGGTGTTCAAGAGAGATGCCCACGGCCAGCAGATGATC TTCCCATATTACGGCAGAGAAGAGGAACTGCGGAAGCACCCCATTAAGAGAGCCGCTGAAGGCTGGGC TGCTCCCGATGCACTTCTGGGACAAGTGAAGGCCTCTCTGCTGCCTGGTGGATCTGAAGGCGGCAGAC GTAGAAGAGAACTGGACCCCATGGATGTGCGGGGCAGCATCGTGTACCTGGAAATCGACAACCGGCAG TGCGTGCAGGCCAGCTCTCAGTGTTTTCAGAGCGCTACAGACGTGGCCGCCTTTCTGGGAGCACTGGC TTCTCTGGGCTCCCTGAACATCCCCTACAAGATCGAGGCCGTGCAGAGCGAGACAGTGGAACCTCCTC CTCCTGCTCAACTGCACTTTATGTACGTGGCCGCTGCTGCCTTCGTGCTGCTGTTCTTTGTTGGCTGC GGAGTGCTGCTGAGCAAGCGGAAGAGAAAGCACGGATCTGGATCAGGCAGCGGAAGCTCTCTGCGCGT GAAGTTCAGCAGATCAGCCGACGCTCCTGCCTATCAGCAGGGCCAGAACCAGCTGTACAACGAGCTGA ACCTGGGGAGAAGAGAAGAGTACGACGTGCTGGACAAGCGGAGAGGCAGAGATCCTGAGATGGGCGGA AAGCCCCAGCGGAGAAAGAATCCTCAAGAGGGCCTGTATAATGAGCTGCAGAAAGACAAGATGGCCGA GGCCTACAGCGAGATCGGAATGAAGGGCGAGCGCAGAAGAGGCAAGGGACACGATGGACTGTACCAGG GCCTGAGCACCGCCACCAAGGATACCTATGATGCCCTGCACATGCAGGCCCTGCCTCCAAGAAAGCGG GGCAGAAAGAAGCTGCTGTACATCTTCAAGCAGCCCTTCATGCGGCCCGTGCAGACCACACAAGAGGA AGATGGCTGCTCCTGCAGATTCCCCGAGGAAGAAGAAGGCGGCTGCGAACTTGGAGGCGGCGGATCTT ATAGACCCGCCAGAGTGACCAGCACCAGCCGGTTTCTGAACCCCTACGTCGTGTGCTTCATTGTGGTG GCCGGCGTTGTGATCCTGGCCGTGACAATTGCCCTGCTGGTGTACTTCCTGGCCTTCGACCAGAAGTC CTACTTCAGCACCCTGGAAATCTCTGGCGGAGGCGGAGGATCTGGTGGCGGAGGAAGCGGTGGCGGCG GTTCTGACATCCAGATGACCCAGACCACAAGCAGCCTGTCTGCCAGCCTGGGCGATAGAGTGACCATC AGCTGTAGAGCCAGCCAGGACATCAGCAAGTACCTGAACTGGTATCAGCAAAAGCCCGACGGCACCGT GAAGCTGCTGATCTACCACACCAGCAGACTGCACAGCGGCGTGCCAAGCAGATTTTCTGGCAGCGGCT CTGGCACCGACTACAGCCTGACAATCAGCAACCTGGAACAAGAGGATATCGCTACCTACTTCTGCCAG CAAGGCAACACCCTGCCTTACACCTTTGGCGGAGGCACCAAGCTGGAAATCACCGGCTCTACAAGCGG CAGCGGCAAACCTGGATCTGGCGAGGGATCTACCAAGGGCGAAGTGAAACTGCAAGAGTCTGGCCCTG GACTGGTGGCCCCATCTCAGTCTCTGAGCGTGACCTGTACAGTCAGCGGAGTGTCCCTGCCTGATTAC GGCGTGTCCTGGATCAGACAGCCTCCTCGGAAAGGCCTGGAATGGCTGGGAGTGATCTGGGGCAGCGA GACAACCTACTACAACAGCGCCCTGAAGTCCCGGCTGACCATCATCAAGGACAACTCCAAGAGCCAGG TGTTCCTGAAGATGAACAGCCTGCAGACCGACGACACCGCCATCTACTATTGCGCCAAGCACTACTAC TACGGCGGCAGCTACGCCATGGATTATTGGGGCCAGGGCACCAGCGTGACCGTTTCTTCTGCCGCCGC TGACTACAAGGACGACGACGACAAGCGGGCCAAACGATCTGGCTCTGGCCAGTGTACCAACTATGCCC TGCTCAAGCTCGCTGGCGACGTCGAGTCTAACCCTGGACCAATGGGAGCTGGCGCTACAGGCAGAGCT ATGGATGGACCTAGACTGCTGCTGCTCCTGCTTCTGGGAGTGTCTCTTGGCGGAGCCAAAGAGGCCTG TCCTACCGGCCTGTATACACACTCTGGCGAGTGCTGCAAGGCCTGCAATCTTGGAGAAGGCGTCGCAC AGCCTTGCGGCGCTAATCAGACAGTGTGCGAGCCTTGCCTGGACAGCGTGACCTTTAGCGACGTGGTG TCAGCCACCGAGCCATGCAAGCCATGTACCGAGTGTGTGGGCCTGCAGAGCATGTCTGCCCCTTGCGT GGAAGCTGACGATGCCGTGTGTAGATGCGCCTACGGCTACTACCAGGACGAGACAACAGGCAGATGCG AGGCCTGTAGAGTGTGCGAAGCTGGATCTGGCCTGGTGTTCAGCTGCCAAGACAAGCAGAACACCGTG TGCGAGGAATGCCCCGATGGCACCTATAGCGACGAGGCCAACCATGTGGATCCCTGCCTGCCTTGTACAttorney Docket No. 44807-0518WO1 / P18835-01CGTGTGTGAAGATACCGAGCGGCAGCTGCGCGAGTGTACAAGATGGGCTGATGCCGAGTGCGAAGAGA TCCCTGGCAGATGGATCACCAGAAGCACACCTCCAGAGGGCAGCGATAGCACAGCCCCTTCTACACAA GAGCCCGAGGCTCCTCCTGAGCAGGACCTGATTGCTTCTACAGTGGCTGGCGTCGTGACCACCGTGAT GGGATCTAGTCAGCCCGTGGTCACCAGAGGCACCACCGACAATCTGATCCCCGTGTACTGTAGCATCC TGGCCGCCGTGGTTGTTGGACTGGTGGCCTATATCGCCTTCAAGCGGTGGAACAGCTGA(SEQ ID NO: 121)MANTIS-3 DesignCD8a SP - myc tag - BB7.2 - CD45 ECD - human NOTCH1 NRR - NOTCH1 TMD - NOTCH2 JMD - RAM7 - Linker 2 - CD3z Signaling - 41BB CoStim - G4S - TM1 ID JMD - TM1 ID TMD -G4Sx3 - FMC63 - FLAG tag - E2A - tNGFRAmino Acid Sequence for MANTIS-3 MALPVTALLLPLALLLHAARPEQKLISEEDLQVQLQQSGPELVKPGASVKMSCKASGYTFTSYHIQWV KQRPGQGLEWIGWIYPGDGSTQYNEKFKGKTTLTADKSSSTAYMLLSSLTSEDSAIYFCAREGTYYAM DYWGQGTSVTVSSGGGGSGGGGSGGGGSDIVMTQAPLSLPVSLGDQVSISCRSSQSIVHSNGNTYLEW YLQKPGQSPKLLIYKVSNRFSGVPDRFSGSGSGTDFTLKISRVEAEDLGVYYCFQGSHVPRT FGGGTK LELKRTQSPTPSPTGLTTAKMPSVPLSSDPLPTHTTAFSPASTFERENDFSETTTSLSPDNTSTQVSP DSLDNASAFNTTGVSSVQTPHLPTHADSQTPSAGTDTQTFSGSAANAKLNPTPGSNAISDVPGERSTA STFPTDPVSPLTTTLSLAHHSSAALPARTSNTTITANTSDAYLNASETTTLSPSGSAVISTTTIATTP SKPTCDEKYANITVDYLYNKETKLFTAKLNVNENVECGNNTCTNNEVHNLTECKNASVSISHNSCTAP DKTLILDVPPGVEKFQLHDCTQVEKADTTICLKWKNIETFTCDTQNITYRFQCGNMIFDNKEIKLENL EPEHEYKCDSEILYNNHKFTNASKIIKTDFGSPGEPQIIFCRSEAAHQGVITWNPPQRSFHNFTLCYI KETEKDCLNLDKNLIKYDLQNLKPYTKYVLSLHAYIIAKVQRNGSAAMCHFTTKSAPPSQVWNMTVSM TSDNSMHVKCRPPRDRNGPHERYHLEVEAGNTLVRNESHKNCDFRVKDLQYSTDYTFKAYFHNGDYPG EPFILHHSTSYNSKILDYSFGGGAGRDIPPPLIEEACELPECQEDAGNKVCSLQCNNHACGWDGGDCS LNFNDPWKNCTQSLQCWKYFSDGHCDSQCNSAGCLFDGFDCQRAEGQCNPLYDQYCKDHFSDGHCDQG CNSAECEWDGLDCAEHVPERLAAGTLVVVVLMPPEQLRNSSFHFLRELSRVLHTNVVFKRDAHGQQMI FPYYGREEELRKHPIKRAAEGWAAPDALLGQVKASLLPGGSEGGRRRRELDPMDVRGSIVYLEIDNRQ CVQASSQCFQSATDVAAFLGALASLGSLNIPYKIEAVQSETVEPPPPAQLHFMYVAAAAFVLLFFVGC GVLLSKRKRKHQHGQLWFGSGSGSGSSLRVKFSRSADAPAYQQGQNQLYNELNLGRREEYDVLDKRRG RDPEMGGKPQRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQ ALPPRKRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCELGGGGSYRPARVTSTSRFLNPY VVCFIVVAGVVILAVTIALLVY FLAFDQKSYFSTLEISGGGGGSGGGGSGGGGSDIQMTQTTSSLSAS LGDRVTISCRASQDISKYLNWYQQKPDGTVKLLIYHTSRLHSGVPSRFSGSGSGTDYSLTISNLEQED IATYFCQQGNTLPYTFGGGTKLEITGSTSGSGKPGSGEGSTKGEVKLQESGPGLVAPSQSLSVTCTVS GVSLPDYGVSWIRQPPRKGLEWLGVIWGSETTYYNSALKSRLTIIKDNSKSQVFLKMNSLQTDDTAIY YCAKHYYYGGSYAMDYWGQGTSVTVSSAAADYKDDDDKRAKRSGSGQCTNYALLKLAGDVESNPGPMG AGATGRAMDGPRLLLLLLLGVSLGGAKEACPTGLYTHSGECCKACNLGEGVAQPCGANQTVCEPCLDS VTFSDVVSATEPCKPCTECVGLQSMSAPCVEADDAVCRCAYGYYQDETTGRCEACRVCEAGSGLVFSC QDKQNTVCEECPDGTYSDEANHVDPCLPCTVCEDTERQLRECTRWADAECEEIPGRWITRSTPPEGSDAttorney Docket No. 44807-0518WO1 / P18835-01Nucleic Acid Sequence for MANTIS-3 ATGGCTCTGCCTGTGACAGCTCTGCTGCTGCCTCTGGCTCTGCTTCTGCATGCCGCTAGACCTGAGCA GAAGCTGATCTCCGAAGAGGACCTGCAGGTTCAGCTGCAGCAGTCTGGACCTGAGCTGGTTAAGCCTG GCGCTTCCGTGAAGATGAGCTGCAAGGCCAGCGGCTACACCTTCACCAGCTACCACATCCAGTGGGTC AAGCAGAGGCCTGGACAGGGACTCGAGTGGATCGGCTGGATCTATCCTGGCGACGGCAGCACCCAGTA CAACGAGAAGTTCAAGGGCAAGACCACACTGACCGCCGACAAGAGCAGCAGCACAGCCTACATGCTGC TGAGCAGCCTGACCAGCGAGGACAGCGCCATCTACTTTTGTGCCAGAGAGGGCACCTACTACGCCATG GATTATTGGGGCCAGGGCACCAGCGTGACAGTCTCTTCTGGTGGCGGAGGATCTGGCGGAGGTGGAAG CGGCGGAGGCGGATCTGATATCGTGATGACACAGGCCCCTCTGAGCCTGCCTGTGTCTCTGGGAGATC AGGTGTCCATCAGCTGTCGGAGCAGCCAGAGCATCGTGCACAGCAACGGCAACACCTACCTGGAATGG TATCTGCAGAAGCCCGGACAGAGCCCCAAGCTGCTGATCTACAAGGTGTCCAACCGGTTCAGCGGCGT GCCCGATAGATTTTCTGGCTCTGGCAGCGGCACCGACTTCACCCTGAAGATCTCTAGAGTGGAAGCCG AGGACCTGGGCGTGTACTACTGCTTCCAAGGCAGCCACGTGCCAAGAACCTTTGGCGGCGGAACAAAG CTGGAACTGAAGCGGACACAGAGCCCCACACCATCTCCAACAGGACTGACCACCGCCAAGATGCCTAG CGTGCCCCTCTCTTCTGACCCTCTGCCTACACACACCACCGCTTTTAGCCCTGCCAGCACCTTCGAGA GAGAGAACGACTTCAGCGAGACAACCACCTCTCTGAGCCCCGACAACACCAGCACACAGGTGTCCCCA GACAGCCTGGATAATGCCAGCGCCTTCAATACCACCGGCGTGTCCTCTGTGCAGACCCCTCATCTGCC AACACACGCCGATAGCCAGACACCTTCTGCCGGCACCGATACACAGACCTTTTCTGGCTCTGCCGCCA ACGCCAAGCTGAACCCTACACCTGGCAGCAACGCCATCTCTGATGTGCCTGGCGAGAGAAGCACCGCC AGCACATTTCCAACAGACCCCGTGTCTCCCCTGACCACCACACTGTCTCTGGCCCACCATAGCTCTGC TGCCCTGCCTGCCAGAACCAGCAACACCACCATCACCGCCAATACCAGCGACGCCTACCTGAACGCCA GCGAAACCACAACACTGAGCCCTAGCGGAAGCGCCGTGATCAGCACAACCACAATCGCCACCACACCT AGCAAGCCTACCTGCGACGAGAAGTACGCCAACATCACCGTGGACTACCTGTACAACAAAGAGACAAA GCTGTTCACGGCCAAGCTCAACGTGAACGAGAACGTGGAATGCGGCAACAATACCTGCACCAACAACG AGGTGCACAACCTGACCGAGTGCAAGAACGCCTCCGTGTCCATCAGCCACAACAGCTGCACAGCCCCT GACAAGACCCTGATCCTGGATGTGCCTCCTGGCGTGGAAAAGTTCCAGCTGCACGATTGCACCCAGGT GGAAAAGGCCGATACCACCATCTGCCTGAAGTGGAAGAACATCGAGACATTCACCTGTGACACCCAGA ACATCACCTACCGGTTCCAGTGCGGCAATATGATCTTCGATAACAAAGAAATCAAGCTCGAGAACCTC GAGCCTGAGCACGAGTACAAGTGCGACAGCGAGATCCTGTATAACAATCACAAGTTCACCAACGCCAG CAAGATCATCAAGACCGACTTCGGCTCTCCCGGCGAGCCCCAGATCATCTTCTGTAGATCTGAGGCCG CTCACCAGGGCGTGATCACCTGGAATCCTCCACAGCGGAGCTTCCACAACTTCACCCTGTGCTACATC AAAGAAACCGAGAAGGACTGCCTGAACCTGGACAAGAACCTCATTAAGTACGACCTGCAGAACCTGAA GCCGTACACCAAATACGTGCTGAGCCTGCACGCCTACATCATTGCCAAGGTGCAGAGAAATGGCAGCG CCGCCATGTGCCACTTCACCACAAAAAGCGCCCCTCCAAGCCAAGTGTGGAACATGACCGTGTCTATG ACCAGCGACAACTCCATGCACGTGAAGTGCCGGCCTCCACGGGATAGAAATGGCCCTCACGAGAGATA CCACCTGGAAGTCGAGGCCGGAAATACCCTCGTGCGGAACGAGAGCCACAAGAACTGCGACTTCAGAG TGAAGGACCTGCAGTACAGCACCGACTACACCTTCAAGGCCTACTTCCACAATGGCGACTACCCTGGC GAGCCCTTCATCCTGCACCACAGCACCAGCTACAACAGCAAGATCCTGGACTACAGCTTCGGCGGAGG CGCCGGAAGAGATATTCCTCCACCTCTGATCGAGGAAGCCTGCGAGCTGCCTGAGTGTCAAGAGGACG CCGGCAACAAAGTGTGCAGCCTGCAGTGCAACAATCACGCCTGTGGATGGGATGGCGGCGACTGCAGC CTGAACTTCAACGACCCCTGGAAGAACTGCACCCAGTCTCTGCAGTGCTGGAAGTACTTTAGCGACGG CCACTGCGACAGCCAGTGTAATTCTGCCGGCTGCCTGTTCGACGGCTTCGATTGTCAGCGAGCCGAGG GCCAATGCAACCCTCTGTACGACCAGTACTGCAAGGACCACTTCTCCGATGGCCACTGTGACCAGGGC TGTAATAGCGCCGAGTGCGAGTGGGATGGACTGGATTGTGCCGAGCACGTGCCAGAAAGACTGGCCGC TGGAACACTGGTGGTGGTCGTTCTGATGCCTCCTGAGCAGCTGCGGAACAGCAGCTTCCACTTCCTGC GGGAACTGAGCAGAGTGCTGCACACCAACGTGGTGTTCAAGAGAGATGCCCACGGCCAGCAGATGATC TTCCCATATTACGGCAGAGAAGAGGAACTGCGGAAGCACCCCATTAAGAGAGCCGCTGAAGGCTGGGC TGCTCCCGATGCACTTCTGGGACAAGTGAAGGCCTCTCTGCTGCCTGGTGGATCTGAAGGCGGCAGAC GTAGAAGAGAACTGGACCCCATGGATGTGCGGGGCAGCATCGTGTACCTGGAAATCGACAACCGGCAGAttorney Docket No. 44807-0518WO1 / P18835-01TGCGTGCAGGCCAGCTCTCAGTGTTTTCAGAGCGCTACAGACGTGGCCGCCTTTCTGGGAGCACTGGC TTCTCTGGGCTCCCTGAACATCCCCTACAAGATCGAGGCCGTGCAGAGCGAGACAGTGGAACCTCCTC CTCCTGCTCAACTGCACTTTATGTACGTGGCCGCTGCTGCCTTCGTGCTGCTGTTCTTTGTTGGCTGC GGAGTGCTGCTGAGCAAGCGGAAGAGAAAGCACCAGCATGGCCAGCTGTGGTTCGGATCTGGATCAGG CAGCGGAAGCTCTCTGCGCGTGAAGTTCAGCAGATCAGCCGACGCTCCTGCCTATCAGCAGGGCCAGA ACCAGCTGTACAACGAGCTGAACCTGGGGAGAAGAGAAGAGTACGACGTGCTGGACAAGCGGAGAGGC AGAGATCCTGAGATGGGCGGAAAGCCCCAGCGGAGAAAGAATCCTCAAGAGGGCCTGTATAATGAGCT GCAGAAAGACAAGATGGCCGAGGCCTACAGCGAGATCGGAATGAAGGGCGAGCGCAGAAGAGGCAAGG GACACGATGGACTGTACCAGGGCCTGAGCACCGCCACCAAGGATACCTATGATGCCCTGCACATGCAG GCCCTGCCTCCAAGAAAGCGGGGCAGAAAGAAGCTGCTGTACATCTTCAAGCAGCCCTTCATGCGGCC CGTGCAGACCACACAAGAGGAAGATGGCTGCTCCTGCAGATTCCCCGAGGAAGAAGAAGGCGGCTGCG AACTTGGAGGCGGCGGATCTTATAGACCCGCCAGAGTGACCAGCACCAGCCGGTTTCTGAACCCCTAC GTCGTGTGCTTCATTGTGGTGGCCGGCGTTGTGATCCTGGCCGTGACAATTGCCCTGCTGGTGTACTT CCTGGCCTTCGACCAGAAGTCCTACTTCAGCACCCTGGAAATCTCTGGCGGAGGCGGAGGATCTGGTG GCGGAGGAAGCGGTGGCGGCGGTTCTGACATCCAGATGACCCAGACCACAAGCAGCCTGTCTGCCAGC CTGGGCGATAGAGTGACCATCAGCTGTAGAGCCAGCCAGGACATCAGCAAGTACCTGAACTGGTATCA GCAAAAGCCCGACGGCACCGTGAAGCTGCTGATCTACCACACCAGCAGACTGCACAGCGGCGTGCCAA GCAGATTTTCTGGCAGCGGCTCTGGCACCGACTACAGCCTGACAATCAGCAACCTGGAACAAGAGGAT ATCGCTACCTACTTCTGCCAGCAAGGCAACACCCTGCCTTACACCTTTGGCGGAGGCACCAAGCTGGA AATCACCGGCTCTACAAGCGGCAGCGGCAAACCTGGATCTGGCGAGGGATCTACCAAGGGCGAAGTGA AACTGCAAGAGTCTGGCCCTGGACTGGTGGCCCCATCTCAGTCTCTGAGCGTGACCTGTACAGTCAGC GGAGTGTCCCTGCCTGATTACGGCGTGTCCTGGATCAGACAGCCTCCTCGGAAAGGCCTGGAATGGCT GGGAGTGATCTGGGGCAGCGAGACAACCTACTACAACAGCGCCCTGAAGTCCCGGCTGACCATCATCA AGGACAACTCCAAGAGCCAGGTGTTCCTGAAGATGAACAGCCTGCAGACCGACGACACCGCCATCTAC TATTGCGCCAAGCACTACTACTACGGCGGCAGCTACGCCATGGATTATTGGGGCCAGGGCACCAGCGT GACCGTTTCTTCTGCCGCCGCTGACTACAAGGACGACGACGACAAGCGGGCCAAACGATCTGGCTCTG GCCAGTGTACCAACTATGCCCTGCTCAAGCTCGCTGGCGACGTCGAGTCTAACCCTGGACCAATGGGA GCTGGCGCTACAGGCAGAGCTATGGATGGACCTAGACTGCTGCTGCTCCTGCTTCTGGGAGTGTCTCT TGGCGGAGCCAAAGAGGCCTGTCCTACCGGCCTGTATACACACTCTGGCGAGTGCTGCAAGGCCTGCA ATCTTGGAGAAGGCGTCGCACAGCCTTGCGGCGCTAATCAGACAGTGTGCGAGCCTTGCCTGGACAGC GTGACCTTTAGCGACGTGGTGTCAGCCACCGAGCCATGCAAGCCATGTACCGAGTGTGTGGGCCTGCA GAGCATGTCTGCCCCTTGCGTGGAAGCTGACGATGCCGTGTGTAGATGCGCCTACGGCTACTACCAGG ACGAGACAACAGGCAGATGCGAGGCCTGTAGAGTGTGCGAAGCTGGATCTGGCCTGGTGTTCAGCTGC CAAGACAAGCAGAACACCGTGTGCGAGGAATGCCCCGATGGCACCTATAGCGACGAGGCCAACCATGT GGATCCCTGCCTGCCTTGTACCGTGTGTGAAGATACCGAGCGGCAGCTGCGCGAGTGTACAAGATGGG CTGATGCCGAGTGCGAAGAGATCCCTGGCAGATGGATCACCAGAAGCACACCTCCAGAGGGCAGCGAT AGCACAGCCCCTTCTACACAAGAGCCCGAGGCTCCTCCTGAGCAGGACCTGATTGCTTCTACAGTGGC TGGCGTCGTGACCACCGTGATGGGATCTAGTCAGCCCGTGGTCACCAGAGGCACCACCGACAATCTGA TCCCCGTGTACTGTAGCATCCTGGCCGCCGTGGTTGTTGGACTGGTGGCCTATATCGCCTTCAAGCGG TGGAACAGCTGA(SEQ ID NO: 122)MANTIS-4 DesignCD8a SP - mvc tag - BB7.2 - CD45 ECD - murine NOTCH1 NRR - NOTCH1 TMD - NOTCH2 JMD - Linker 2 - CD3z Signaling - 41BB CoStim - G4S - TM1 ID JMD - TM1 ID TMD - G4Sx3 - FMC63 - FLAG tag - E2A - tNGFRAttorney Docket No. 44807-0518WO1 / P18835-01 Amino Acid Sequence for MANTIS-4 MALPVTALLLPLALLLHAARPEQKLISEEDLQVQLQQSGPELVKPGASVKMSCKASGYTFTSYHIQWV KQRPGQGLEWIGWIYPGDGSTQYNEKFKGKTTLTADKSSSTAYMLLSSLTSEDSAIYFCAREGTYYAM DYWGQGTSVTVSSGGGGSGGGGSGGGGSDIVMTQAPLSLPVSLGDQVSISCRSSQSIVHSNGNTYLEW YLQKPGQSPKLLIYKVSNRFSGVPDRFSGSGSGTDFTLKISRVEAEDLGVYYCFQGSHVPRTFGGGTK LELKRTQSPTPSPTGLTTAKMPSVPLSSDPLPTHTTAFSPASTFERENDFSETTTSLSPDNTSTQVSP DSLDNASAFNTTGVSSVQTPHLPTHADSQTPSAGTDTQTFSGSAANAKLNPTPGSNAISDVPGERSTA STFPTDPVSPLTTTLSLAHHSSAALPARTSNTTITANTSDAYLNASETTTLSPSGSAVISTTTIATTP SKPTCDEKYANITVDYLYNKETKLFTAKLNVNENVECGNNTCTNNEVHNLTECKNASVSISHNSCTAP DKTLILDVPPGVEKFQLHDCTQVEKADTTICLKWKNIETFTCDTQNITYRFQCGNMIFDNKEIKLENL EPEHEYKCDSEILYNNHKFTNASKIIKTDFGSPGEPQIIFCRSEAAHQGVITWNPPQRSFHNFTLCYI KETEKDCLNLDKNLIKYDLQNLKPYTKYVLSLHAYIIAKVQRNGSAAMCHFTTKSAPPSQVWNMTVSM TSDNSMHVKCRPPRDRNGPHERYHLEVEAGNTLVRNESHKNCDFRVKDLQYSTDYTFKAYFHNGDYPG EPFILHHSTSYNSKILDYSFTGGAGRDIPPPQIEEACELPECQVDAGNKVCNLQCNNHACGWDGGDCS LNFNDPWKNCTQSLQCWKYFSDGHCDSQCNSAGCLFDGFDCQLTEGQCNPLYDQYCKDHFSDGHCDQG CNSAECEWDGLDCAEHVPERLAAGTLVLVVLLPPDQLRNNSFHFLRELSHVLHTNVVFKRDAQGQQMI FPYYGHEEELRKHPIKRSTVGWATSSLLPGTSGGRQRRELDPMDIRGSIVYLEIDNRQCVQSSSQCFQ SATDVAAFLGALASLGSLNIPYKIEAVKSEPVEPPLPSQFMYVAAAAFVLLFFVGCGVLLSKRKRKHG SGSGSGSSLRVKFSRSADAPAYQQGQNQLYNELNLGRREEYDVLDKRRGRDPEMGGKPQRRKNPQEGL YNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPRKRGRKKLLYIFKQP FMRPVQTTQEEDGCSCRFPEEEEGGCELGGGGSYRPARVTSTSRFLNPYVVCFIVVAGVVILAVTIAL LVYFLAFDQKSYFSTLEISGGGGGSGGGGSGGGGSDIQMTQTTSSLSASLGDRVTISCRASQDISKYL NWYQQKPDGTVKLLIYHTSRLHSGVPSRFSGSGSGTDYSLTISNLEQEDIATYFCQQGNTLPYTFGGG TKLEITGSTSGSGKPGSGEGSTKGEVKLQESGPGLVAPSQSLSVTCTVSGVSLPDYGVSWIRQPPRKG LEWLGVIWGSETTYYNSALKSRLTIIKDNSKSQVFLKMNSLQTDDTAIYYCAKHYYYGGSYAMDYWGQ GTSVTVSSAAADYKDDDDKRAKRSGSGQCTNYALLKLAGDVESNPGPMGAGATGRAMDGPRLLLLLLL GVSLGGAKEACPTGLYTHSGECCKACNLGEGVAQPCGANQTVCEPCLDSVTFSDVVSATEPCKPCTEC VGLQSMSAPCVEADDAVCRCAYGYYQDETTGRCEACRVCEAGSGLVFSCQDKQNTVCEECPDGTYSDE ANHVDPCLPCTVCEDTERQLRECTRWADAECEEIPGRWITRSTPPEGSDSTAPSTQEPEAPPEQDLIANucleic Acid Sequence for MANTIS-4 ATGGCTCTGCCTGTGACAGCTCTGCTGCTGCCTCTGGCTCTGCTTCTGCATGCCGCTAGACCTGAGCA GAAGCTGATCTCCGAAGAGGACCTGCAGGTTCAGCTGCAGCAGTCTGGACCTGAGCTGGTTAAGCCTG GCGCTTCCGTGAAGATGAGCTGCAAGGCCAGCGGCTACACCTTCACCAGCTACCACATCCAGTGGGTC AAGCAGAGGCCTGGACAGGGACTCGAGTGGATCGGCTGGATCTATCCTGGCGACGGCAGCACCCAGTA CAACGAGAAGTTCAAGGGCAAGACCACACTGACCGCCGACAAGAGCAGCAGCACAGCCTACATGCTGC TGAGCAGCCTGACCAGCGAGGACAGCGCCATCTACTTTTGTGCCAGAGAGGGCACCTACTACGCCATG GATTATTGGGGCCAGGGCACCAGCGTGACAGTCTCTTCTGGTGGCGGAGGATCTGGCGGAGGTGGAAG CGGCGGAGGCGGATCTGATATCGTGATGACACAGGCCCCTCTGAGCCTGCCTGTGTCTCTGGGAGATC AGGTGTCCATCAGCTGTCGGAGCAGCCAGAGCATCGTGCACAGCAACGGCAACACCTACCTGGAATGG TATCTGCAGAAGCCCGGACAGAGCCCCAAGCTGCTGATCTACAAGGTGTCCAACCGGTTCAGCGGCGT GCCCGATAGATTTTCTGGCTCTGGCAGCGGCACCGACTTCACCCTGAAGATCTCTAGAGTGGAAGCCG AGGACCTGGGCGTGTACTACTGCTTCCAAGGCAGCCACGTGCCAAGAACCTTTGGCGGCGGAACAAAG CTGGAACTGAAGCGGACACAGAGCCCCACACCATCTCCAACAGGACTGACCACCGCCAAGATGCCTAG CGTGCCCCTCTCTTCTGACCCTCTGCCTACACACACCACCGCTTTTAGCCCTGCCAGCACCTTCGAGAAttorney Docket No. 44807-0518WO1 / P18835-01GAGAGAACGACTTCAGCGAGACAACCACCTCTCTGAGCCCCGACAACACCAGCACACAGGTGTCCCCA GACAGCCTGGATAATGCCAGCGCCTTCAATACCACCGGCGTGTCCTCTGTGCAGACCCCTCATCTGCC AACACACGCCGATAGCCAGACACCTTCTGCCGGCACCGATACACAGACCTTTTCTGGCTCTGCCGCCA ACGCCAAGCTGAACCCTACACCTGGCAGCAACGCCATCTCTGATGTGCCTGGCGAGAGAAGCACCGCC AGCACATTTCCAACAGACCCCGTGTCTCCCCTGACCACCACACTGTCTCTGGCCCACCATAGCTCTGC TGCCCTGCCTGCCAGAACCAGCAACACCACCATCACCGCCAATACCAGCGACGCCTACCTGAACGCCA GCGAAACCACAACACTGAGCCCTAGCGGAAGCGCCGTGATCAGCACAACCACAATCGCCACCACACCT AGCAAGCCTACCTGCGACGAGAAGTACGCCAACATCACCGTGGACTACCTGTACAACAAAGAGACAAA GCTGTTCACGGCCAAGCTCAACGTGAACGAGAACGTGGAATGCGGCAACAATACCTGCACCAACAACG AGGTGCACAACCTGACCGAGTGCAAGAACGCCTCCGTGTCCATCAGCCACAACAGCTGCACAGCCCCT GACAAGACCCTGATCCTGGATGTGCCTCCTGGCGTGGAAAAGTTCCAGCTGCACGATTGCACCCAGGT GGAAAAGGCCGATACCACCATCTGCCTGAAGTGGAAGAACATCGAGACATTCACCTGTGACACCCAGA ACATCACCTACCGGTTCCAGTGCGGCAATATGATCTTCGATAACAAAGAAATCAAGCTCGAGAACCTC GAGCCTGAGCACGAGTACAAGTGCGACAGCGAGATCCTGTATAACAATCACAAGTTCACCAACGCCAG CAAGATCATCAAGACCGACTTCGGCTCTCCCGGCGAGCCCCAGATCATCTTCTGTAGATCTGAGGCCG CTCACCAGGGCGTGATCACCTGGAATCCTCCACAGCGGAGCTTCCACAACTTCACCCTGTGCTACATC AAAGAAACCGAGAAGGACTGCCTGAACCTGGACAAGAACCTCATTAAGTACGACCTGCAGAACCTGAA GCCGTACACCAAATACGTGCTGAGCCTGCACGCCTACATCATTGCCAAGGTGCAGAGAAATGGCAGCG CCGCCATGTGCCACTTCACCACAAAAAGCGCCCCTCCAAGCCAAGTGTGGAACATGACCGTGTCTATG ACCAGCGACAACTCCATGCACGTGAAGTGCCGGCCTCCACGGGATAGAAATGGCCCTCACGAGAGATA CCACCTGGAAGTCGAGGCCGGAAATACCCTCGTGCGGAACGAGAGCCACAAGAACTGCGACTTCAGAG TGAAGGACCTGCAGTACAGCACCGACTACACCTTCAAGGCCTACTTCCACAATGGCGACTACCCTGGC GAGCCCTTCATCCTGCACCACAGCACCAGCTACAACAGCAAGATCCTGGACTACAGCTTCACCGGCGG AGCCGGCAGAGATATTCCTCCACCTCAGATCGAGGAAGCCTGCGAGCTGCCTGAGTGTCAAGTGGACG CCGGCAACAAAGTGTGCAACCTGCAGTGCAACAACCACGCCTGTGGATGGGATGGCGGCGACTGCAGC CTGAACTTCAACGACCCCTGGAAGAACTGCACCCAGAGCCTGCAGTGTTGGAAGTACTTTAGCGACGG CCACTGCGACAGCCAGTGTAATTCTGCCGGATGCCTGTTCGACGGCTTCGACTGCCAACTGACAGAGG GCCAGTGCAACCCTCTGTACGACCAGTACTGCAAGGACCACTTCTCCGATGGCCACTGTGACCAGGGC TGTAATAGCGCCGAGTGCGAGTGGGATGGACTGGATTGTGCCGAGCACGTGCCAGAAAGACTGGCCGC TGGAACACTGGTGCTGGTTGTTCTGCTGCCTCCTGACCAGCTGCGGAACAACAGCTTCCACTTCCTGC GGGAACTGAGCCACGTGCTGCACACCAACGTGGTGTTCAAGAGAGATGCCCAGGGCCAGCAGATGATC TTCCCCTACTATGGCCACGAAGAGGAACTGCGGAAGCACCCCATCAAGAGAAGCACAGTTGGCTGGGC CACCAGCTCACTGCTGCCTGGAACATCTGGCGGCAGACAGAGAAGAGAACTGGACCCCATGGACATCC GGGGCAGCATCGTGTACCTGGAAATCGACAACCGGCAGTGCGTGCAGAGCAGCAGCCAGTGCTTTCAG AGCGCTACAGATGTGGCCGCCTTTCTGGGAGCACTGGCATCTCTGGGCTCCCTGAACATCCCCTACAA GATCGAGGCCGTGAAGTCCGAGCCTGTGGAACCTCCATTGCCTAGCCAGTTTATGTACGTGGCCGCTG CTGCCTTCGTGCTGCTGTTCTTTGTTGGCTGCGGAGTGCTGCTGAGCAAGCGGAAGAGAAAGCACGGA TCTGGATCAGGCAGCGGAAGCTCTCTGCGCGTGAAGTTCAGCAGATCAGCCGACGCTCCTGCCTATCA GCAGGGCCAGAACCAGCTGTACAACGAGCTGAACCTGGGGAGAAGAGAAGAGTACGACGTGCTGGACA AGCGGAGAGGCAGAGATCCTGAGATGGGCGGAAAGCCCCAGCGGAGAAAGAATCCTCAAGAGGGCCTG TATAATGAGCTGCAGAAAGACAAGATGGCCGAGGCCTACAGCGAGATCGGAATGAAGGGCGAGCGCAG AAGAGGCAAGGGACACGATGGACTGTACCAGGGCCTGAGCACCGCCACCAAGGATACCTATGATGCCC TGCACATGCAGGCCCTGCCTCCAAGAAAGCGGGGCAGAAAGAAGCTGCTGTACATCTTCAAGCAGCCC TTCATGCGGCCCGTGCAGACCACACAAGAGGAAGATGGCTGCTCCTGCAGATTCCCCGAGGAAGAAGA AGGCGGCTGCGAACTTGGAGGCGGCGGATCTTATAGACCCGCCAGAGTGACCAGCACCAGCCGGTTTC TGAACCCCTACGTCGTGTGCTTCATTGTGGTGGCCGGCGTTGTGATCCTGGCCGTGACAATTGCCCTG CTGGTGTACTTCCTGGCCTTCGACCAGAAGTCCTACTTCAGCACCCTGGAAATCTCTGGCGGAGGCGG AGGATCTGGTGGCGGAGGAAGCGGTGGCGGCGGTTCTGACATCCAGATGACCCAGACCACAAGCAGCC TGTCTGCCAGCCTGGGCGATAGAGTGACCATCAGCTGTAGAGCCAGCCAGGACATCAGCAAGTACCTGAttorney Docket No. 44807-0518WO1 / P18835-01AACTGGTATCAGCAAAAGCCCGACGGCACCGTGAAGCTGCTGATCTACCACACCAGCAGACTGCACAG CGGCGTGCCAAGCAGATTTTCTGGCAGCGGCTCTGGCACCGACTACAGCCTGACAATCAGCAACCTGG AACAAGAGGATATCGCTACCTACTTCTGCCAGCAAGGCAACACCCTGCCTTACACCTTTGGCGGAGGC ACCAAGCTGGAAATCACCGGCTCTACAAGCGGCAGCGGCAAACCTGGATCTGGCGAGGGATCTACCAA GGGCGAAGTGAAACTGCAAGAGTCTGGCCCTGGACTGGTGGCCCCATCTCAGTCTCTGAGCGTGACCT GTACAGTCAGCGGAGTGTCCCTGCCTGATTACGGCGTGTCCTGGATCAGACAGCCTCCTCGGAAAGGC CTGGAATGGCTGGGAGTGATCTGGGGCAGCGAGACAACCTACTACAACAGCGCCCTGAAGTCCCGGCT GACCATCATCAAGGACAACTCCAAGAGCCAGGTGTTCCTGAAGATGAACAGCCTGCAGACCGACGACA CCGCCATCTACTATTGCGCCAAGCACTACTACTACGGCGGCAGCTACGCCATGGATTATTGGGGCCAG GGCACCAGCGTGACCGTTTCTTCTGCCGCCGCTGACTACAAGGACGACGACGACAAGCGGGCCAAACG ATCTGGCTCTGGCCAGTGTACCAACTATGCCCTGCTCAAGCTCGCTGGCGACGTCGAGTCTAACCCTG GACCAATGGGAGCTGGCGCTACAGGCAGAGCTATGGATGGACCTAGACTGCTGCTGCTCCTGCTTCTG GGAGTGTCTCTTGGCGGAGCCAAAGAGGCCTGTCCTACCGGCCTGTATACACACTCTGGCGAGTGCTG CAAGGCCTGCAATCTTGGAGAAGGCGTCGCACAGCCTTGCGGCGCTAATCAGACAGTGTGCGAGCCTT GCCTGGACAGCGTGACCTTTAGCGACGTGGTGTCAGCCACCGAGCCATGCAAGCCATGTACCGAGTGT GTGGGCCTGCAGAGCATGTCTGCCCCTTGCGTGGAAGCTGACGATGCCGTGTGTAGATGCGCCTACGG CTACTACCAGGACGAGACAACAGGCAGATGCGAGGCCTGTAGAGTGTGCGAAGCTGGATCTGGCCTGG TGTTCAGCTGCCAAGACAAGCAGAACACCGTGTGCGAGGAATGCCCCGATGGCACCTATAGCGACGAG GCCAACCATGTGGATCCCTGCCTGCCTTGTACCGTGTGTGAAGATACCGAGCGGCAGCTGCGCGAGTG TACAAGATGGGCTGATGCCGAGTGCGAAGAGATCCCTGGCAGATGGATCACCAGAAGCACACCTCCAG AGGGCAGCGATAGCACAGCCCCTTCTACACAAGAGCCCGAGGCTCCTCCTGAGCAGGACCTGATTGCT TCTACAGTGGCTGGCGTCGTGACCACCGTGATGGGATCTAGTCAGCCCGTGGTCACCAGAGGCACCAC CGACAATCTGATCCCCGTGTACTGTAGCATCCTGGCCGCCGTGGTTGTTGGACTGGTGGCCTATATCG CCTTCAAGCGGTGGAACAGCTGA(SEQ ID NO: 123)MANTIS-5 DesignCD8a SP - myc tag - BB7.2 - CD45 ECD - murine NOTCH1 NRR - NOTCH1 TMD - NOTCH2 JMD - RAM7 - Linker 2 - CD3z Signaling - 41BB CoStim - G4S - TM1 ID JMD - TM1 ID TMD -G4Sx3 - FMC63 - FLAG tag - E2A - tNGFRAmino Acid Sequence for MANTIS-5 MALPVTALLLPLALLLHAARPEQKLISEEDLQVQLQQSGPELVKPGASVKMSCKASGYTFTSYHIQWV KQRPGQGLEWIGWIYPGDGSTQYNEKFKGKTTLTADKSSSTAYMLLSSLTSEDSAIYFCAREGTYYAM DYWGQGTSVTVSSGGGGSGGGGSGGGGSDIVMTQAPLSLPVSLGDQVSISCRSSQSIVHSNGNTYLEW YLQKPGQSPKLLIYKVSNRFSGVPDRFSGSGSGTDFTLKISRVEAEDLGVYYCFQGSHVPRT FGGGTK LELKRTQSPTPSPTGLTTAKMPSVPLSSDPLPTHTTAFSPASTFERENDFSETTTSLSPDNTSTQVSP DSLDNASAFNTTGVSSVQTPHLPTHADSQTPSAGTDTQTFSGSAANAKLNPTPGSNAISDVPGERSTA STFPTDPVSPLTTTLSLAHHSSAALPARTSNTTITANTSDAYLNASETTTLSPSGSAVISTTTIATTP SKPTCDEKYANITVDYLYNKETKLFTAKLNVNENVECGNNTCTNNEVHNLTECKNASVSISHNSCTAP DKTLILDVPPGVEKFQLHDCTQVEKADTTICLKWKNIETFTCDTQNITYRFQCGNMIFDNKEIKLENL EPEHEYKCDSEILYNNHKFTNASKIIKTDFGSPGEPQIIFCRSEAAHQGVITWNPPQRSFHNFTLCYI KETEKDCLNLDKNLIKYDLQNLKPYTKYVLSLHAYIIAKVQRNGSAAMCHFTTKSAPPSQVWNMTVSM TSDNSMHVKCRPPRDRNGPHERYHLEVEAGNTLVRNESHKNCDFRVKDLQYSTDYTFKAYFHNGDYPG EPFILHHSTSYNSKILDYSFTGGAGRDIPPPQIEEACELPECQVDAGNKVCNLQCNNHACGWDGGDCS LNFNDPWKNCTQSLQCWKYFSDGHCDSQCNSAGCLFDGFDCQLTEGQCNPLYDQYCKDHFSDGHCDQG CNSAECEWDGLDCAEHVPERLAAGTLVLVVLLPPDQLRNNSFHFLRELSHVLHTNVVFKRDAQGQQMIAttorney Docket No. 44807-0518WO1 / P18835-01FPYYGHEEELRKHPIKRSTVGWATSSLLPGTSGGRQRRELDPMDIRGSIVYLEIDNRQCVQSSSQCFQ SATDVAAFLGALASLGSLNIPYKIEAVKSEPVEPPLPSQFMYVAAAAFVLLFFVGCGVLLSRKRRRQH GQLWFGSGSGSGSSLRVKFSRSADAPAYQQGQNQLYNELNLGRREEYDVLDKRRGRDPEMGGKPQRRK NPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPRKRGRKKLL YIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCELGGGGSYRPARVTSTSRFLNPYVVCFIVVAGVVIL AVTIALLVYFLAFDQKSYFSTLEISGGGGGSGGGGSGGGGSDIQMTQTTSSLSASLGDRVTISCRASQ DISKYLNWYQQKPDGTVKLLIYHTSRLHSGVPSRFSGSGSGTDYSLTISNLEQEDIATYFCQQGNTLP YTFGGGTKLEITGSTSGSGKPGSGEGSTKGEVKLQESGPGLVAPSQSLSVTCTVSGVSLPDYGVSWIR QPPRKGLEWLGVIWGSETTYYNSALKSRLTIIKDNSKSQVFLKMNSLQTDDTAIYYCAKHYYYGGSYA MDYWGQGTSVTVSSAAADYKDDDDKRAKRSGSGQCTNYALLKLAGDVESNPGPMGAGATGRAMDGPRL LLLLLLGVSLGGAKEACPTGLYTHSGECCKACNLGEGVAQPCGANQTVCEPCLDSVTFSDVVSATEPC KPCTECVGLQSMSAPCVEADDAVCRCAYGYYQDETTGRCEACRVCEAGSGLVFSCQDKQNTVCEECPD GTYSDEANHVDPCLPCTVCEDTERQLRECTRWADAECEEIPGRWITRSTPPEGSDSTAPSTQEPEAPP EQDLIASTVAGVVTTVMGSSQPVVTRGTTDNLIPVYCSILAAVVVGLVAYIAFKRWNS* (SEQ ID NO:8)Nucleic Acid Sequence for MANTIS-5 MALPVTALLLPLALLLHAARPEQKLISEEDLQVQLQQSGPELVKPGASVKMSCKASGYTFTSYHIQWV KQRPGQGLEWIGWIYPGDGSTQYNEKFKGKTTLTADKSSSTAYMLLSSLTSEDSAIYFCAREGTYYAM DYWGQGTSVTVSSGGGGSGGGGSGGGGSDIVMTQAPLSLPVSLGDQVSISCRSSQSIVHSNGNTYLEW YLQKPGQSPKLLIYKVSNRFSGVPDRFSGSGSGTDFTLKISRVEAEDLGVYYCFQGSHVPRT FGGGTK LELKRTQSPTPSPTGLTTAKMPSVPLSSDPLPTHTTAFSPASTFERENDFSETTTSLSPDNTSTQVSP DSLDNASAFNTTGVSSVQTPHLPTHADSQTPSAGTDTQTFSGSAANAKLNPTPGSNAISDVPGERSTA STFPTDPVSPLTTTLSLAHHSSAALPARTSNTTITANTSDAYLNASETTTLSPSGSAVISTTTIATTP SKPTCDEKYANITVDYLYNKETKLFTAKLNVNENVECGNNTCTNNEVHNLTECKNASVSISHNSCTAP DKTLILDVPPGVEKFQLHDCTQVEKADTTICLKWKNIETFTCDTQNITYRFQCGNMIFDNKEIKLENL EPEHEYKCDSEILYNNHKFTNASKIIKTDFGSPGEPQIIFCRSEAAHQGVITWNPPQRSFHNFTLCYI KETEKDCLNLDKNLIKYDLQNLKPYTKYVLSLHAYIIAKVQRNGSAAMCHFTTKSAPPSQVWNMTVSM TSDNSMHVKCRPPRDRNGPHERYHLEVEAGNTLVRNESHKNCDFRVKDLQYSTDYTFKAYFHNGDYPG EPFILHHSTSYNSKILDYSFTGGAGRDIPPPQIEEACELPECQVDAGNKVCNLQCNNHACGWDGGDCS LNFNDPWKNCTQSLQCWKYFSDGHCDSQCNSAGCLFDGFDCQLTEGQCNPLYDQYCKDHFSDGHCDQG CNSAECEWDGLDCAEHVPERLAAGTLVLVVLLPPDQLRNNSFHFLRELSHVLHTNVVFKRDAQGQQMI FPYYGHEEELRKHPIKRSTVGWATSSLLPGTSGGRQRRELDPMDIRGSIVYLEIDNRQCVQSSSQCFQ SATDVAAFLGALASLGSLNIPYKIEAVKSEPVEPPLPSQFMYVAAAAFVLLFFVGCGVLLSRKRRRQH GQLWFGSGSGSGSSLRVKFSRSADAPAYQQGQNQLYNELNLGRREEYDVLDKRRGRDPEMGGKPQRRK NPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPRKRGRKKLL YIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCELGGGGSYRPARVTSTSRFLNPYVVCFIVVAGVVIL AVTIALLVYFLAFDQKSYFSTLEISGGGGGSGGGGSGGGGSDIQMTQTTSSLSASLGDRVTISCRASQ DISKYLNWYQQKPDGTVKLLIYHTSRLHSGVPSRFSGSGSGTDYSLTISNLEQEDIATYFCQQGNTLP YTFGGGTKLEITGSTSGSGKPGSGEGSTKGEVKLQESGPGLVAPSQSLSVTCTVSGVSLPDYGVSWIR QPPRKGLEWLGVIWGSETTYYNSALKSRLTIIKDNSKSQVFLKMNSLQTDDTAIYYCAKHYYYGGSYA MDYWGQGTSVTVSSAAADYKDDDDKRAKRSGSGQCTNYALLKLAGDVESNPGPMGAGATGRAMDGPRL LLLLLLGVSLGGAKEACPTGLYTHSGECCKACNLGEGVAQPCGANQTVCEPCLDSVTFSDVVSATEPC KPCTECVGLQSMSAPCVEADDAVCRCAYGYYQDETTGRCEACRVCEAGSGLVFSCQDKQNTVCEECPD GTYSDEANHVDPCLPCTVCEDTERQLRECTRWADAECEEIPGRWITRSTPPEGSDSTAPSTQEPEAPP EQDLIASTVAGVVTTVMGSSQPVVTRGTTDNLIPVYCSILAAVVVGLVAYIAFKRWNS*(SEQ ID NO: 124)Attorney Docket No. 44807-0518WO1 / P18835-01MANTIS-6 DesignCD8a SP - myc tag - BB7.2 - CD45 ECD - human NOTCH1 NRR dSl- NOTCH1 TMD - NOTCH2 JMD - RAM7 - Linker 2 - CD3z Signaling - 41BB CoStim - G4S - TM1 ID JMD - TM1 ID TMD -G4Sx3 - FMC63 - FLAG tag - E2A - tNGFRAmino Acid Sequence for MANTIS-6 MALPVTALLLPLALLLHAARPEQKLISEEDLQVQLQQSGPELVKPGASVKMSCKASGYTFTSYHIQWV KQRPGQGLEWIGWIYPGDGSTQYNEKFKGKTTLTADKSSSTAYMLLSSLTSEDSAIYFCAREGTYYAM DYWGQGTSVTVSSGGGGSGGGGSGGGGSDIVMTQAPLSLPVSLGDQVSISCRSSQSIVHSNGNTYLEW YLQKPGQSPKLLIYKVSNRFSGVPDRFSGSGSGTDFTLKISRVEAEDLGVYYCFQGSHVPRT FGGGTK LELKRTQSPTPSPTGLTTAKMPSVPLSSDPLPTHTTAFSPASTFERENDFSETTTSLSPDNTSTQVSP DSLDNASAFNTTGVSSVQTPHLPTHADSQTPSAGTDTQTFSGSAANAKLNPTPGSNAISDVPGERSTA STFPTDPVSPLTTTLSLAHHSSAALPARTSNTTITANTSDAYLNASETTTLSPSGSAVISTTTIATTP SKPTCDEKYANITVDYLYNKETKLFT KLNVNENVECGNNTCTNNEVHNLTECKNASVSISHNSCTAP DKTLILDVPPGVEKFQLHDCTQVEKADTTICLKWKNIETFTCDTQNITYRFQCGNMIFDNKEIKLENL EPEHEYKCDSEILYNNHKFTNASKIIKTDFGSPGEPQIIFCRSEAAHQGVITWNPPQRSFHNFTLCYI KETEKDCLNLDKNLIKYDLQNLKPYTKYVLSLHAYIIAKVQRNGSAAMCHFTTKSAPPSQVWNMTVSM TSDNSMHVKCRPPRDRNGPHERYHLEVEAGNTLVRNESHKNCDFRVKDLQYSTDYTFKAYFHNGDYPG EPFILHHSTSYNSKILDYSFGGGAGRDIPPPLIEEACELPECQEDAGNKVCSLQCNNHACGWDGGDCS LNFNDPWKNCTQSLQCWKYFSDGHCDSQCNSAGCLFDGFDCQRAEGQCNPLYDQYCKDHFSDGHCDQG CNSAECEWDGLDCAEHVPERLAAGTLVVVVLMPPEQLRNSSFHFLRELSRVLHTNVVFKRDAHGQQMI FPYYGREEELELDPMDVRGSIVYLEIDNRQCVQASSQCFQSATDVAAFLGALASLGSLNIPYKIEAVQ SETVEPPPPAQLHFMYVAAAAFVLLFFVGCGVLLSKRKRKHQHGQLWFGSGSGSGSSLRVKFSRSADA PAYQQGQNQLYNELNLGRREEYDVLDKRRGRDPEMGGKPQRRKNPQEGLYNELQKDKMAEAYSEIGMK GERRRGKGHDGLYQGLSTATKDTYDALHMQALPPRKRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFP EEEEGGCELGGGGSYRPARVTSTSRFLNPYVVCFIVVAGVVILAVTIALLVYFLAFDQKSYFSTLEIS GGGGGSGGGGSGGGGSDIQMTQTTSSLSASLGDRVTISCRASQDISKYLNWYQQKPDGTVKLLIYHTS RLHSGVPSRFSGSGSGTDYSLTISNLEQEDIATYFCQQGNTLPYTFGGGTKLEITGSTSGSGKPGSGE GSTKGEVKLQESGPGLVAPSQSLSVTCTVSGVSLPDYGVSWIRQPPRKGLEWLGVIWGSETTYYNSAL KSRLTI IKDNSKSQVFLKMNSLQTDDTAIYYCAKHYYYGGSYAMDYWGQGTSVTVSSAAADYKDDDDK RAKRSGSGQCTNYALLKLAGDVESNPGPMGAGATGRAMDGPRLLLLLLLGVSLGGAKEACPTGLYTHS GECCKACNLGEGVAQPCGANQTVCEPCLDSVTFSDVVSATEPCKPCTECVGLQSMSAPCVEADDAVCR CAYGYYQDETTGRCEACRVCEAGSGLVFSCQDKQNTVCEECPDGTYSDEANHVDPCLPCTVCEDTERQ LRECTRWADAECEEIPGRWITRSTPPEGSDSTAPSTQEPEAPPEQDLIASTVAGVVTTVMGSSQPVVTNucleic Acid Sequence for MANTIS-6 ATGGCTCTGCCTGTGACAGCTCTGCTGCTGCCTCTGGCTCTGCTTCTGCATGCCGCTAGACCTGAGCA GAAGCTGATCTCCGAAGAGGACCTGCAGGTTCAGCTGCAGCAGTCTGGACCTGAGCTGGTTAAGCCTG GCGCTTCCGTGAAGATGAGCTGCAAGGCCAGCGGCTACACCTTCACCAGCTACCACATCCAGTGGGTC AAGCAGAGGCCTGGACAGGGACTCGAGTGGATCGGCTGGATCTATCCTGGCGACGGCAGCACCCAGTA CAACGAGAAGTTCAAGGGCAAGACCACACTGACCGCCGACAAGAGCAGCAGCACAGCCTACATGCTGC TGAGCAGCCTGACCAGCGAGGACAGCGCCATCTACTTTTGTGCCAGAGAGGGCACCTACTACGCCATG GATTATTGGGGCCAGGGCACCAGCGTGACAGTCTCTTCTGGTGGCGGAGGATCTGGCGGAGGTGGAAG CGGCGGAGGCGGATCTGATATCGTGATGACACAGGCCCCTCTGAGCCTGCCTGTGTCTCTGGGAGATCAttorney Docket No. 44807-0518WO1 / P18835-01AGGTGTCCATCAGCTGTCGGAGCAGCCAGAGCATCGTGCACAGCAACGGCAACACCTACCTGGAATGG TATCTGCAGAAGCCCGGACAGAGCCCCAAGCTGCTGATCTACAAGGTGTCCAACCGGTTCAGCGGCGT GCCCGATAGATTTTCTGGCTCTGGCAGCGGCACCGACTTCACCCTGAAGATCTCTAGAGTGGAAGCCG AGGACCTGGGCGTGTACTACTGCTTCCAAGGCAGCCACGTGCCAAGAACCTTTGGCGGCGGAACAAAG CTGGAACTGAAGCGGACACAGAGCCCCACACCATCTCCAACAGGACTGACCACCGCCAAGATGCCTAG CGTGCCCCTCTCTTCTGACCCTCTGCCTACACACACCACCGCTTTTAGCCCTGCCAGCACCTTCGAGA GAGAGAACGACTTCAGCGAGACAACCACCTCTCTGAGCCCCGACAACACCAGCACACAGGTGTCCCCA GACAGCCTGGATAATGCCAGCGCCTTCAATACCACCGGCGTGTCCTCTGTGCAGACCCCTCATCTGCC AACACACGCCGATAGCCAGACACCTTCTGCCGGCACCGATACACAGACCTTTTCTGGCTCTGCCGCCA ACGCCAAGCTGAACCCTACACCTGGCAGCAACGCCATCTCTGATGTGCCTGGCGAGAGAAGCACCGCC AGCACATTTCCAACAGACCCCGTGTCTCCCCTGACCACCACACTGTCTCTGGCCCACCATAGCTCTGC TGCCCTGCCTGCCAGAACCAGCAACACCACCATCACCGCCAATACCAGCGACGCCTACCTGAACGCCA GCGAAACCACAACACTGAGCCCTAGCGGAAGCGCCGTGATCAGCACAACCACAATCGCCACCACACCT AGCAAGCCTACCTGCGACGAGAAGTACGCCAACATCACCGTGGACTACCTGTACAACAAAGAGACAAA GCTGTTCACGGCCAAGCTCAACGTGAACGAGAACGTGGAATGCGGCAACAATACCTGCACCAACAACG AGGTGCACAACCTGACCGAGTGCAAGAACGCCTCCGTGTCCATCAGCCACAACAGCTGCACAGCCCCT GACAAGACCCTGATCCTGGATGTGCCTCCTGGCGTGGAAAAGTTCCAGCTGCACGATTGCACCCAGGT GGAAAAGGCCGATACCACCATCTGCCTGAAGTGGAAGAACATCGAGACATTCACCTGTGACACCCAGA ACATCACCTACCGGTTCCAGTGCGGCAATATGATCTTCGATAACAAAGAAATCAAGCTCGAGAACCTC GAGCCTGAGCACGAGTACAAGTGCGACAGCGAGATCCTGTATAACAATCACAAGTTCACCAACGCCAG CAAGATCATCAAGACCGACTTCGGCTCTCCCGGCGAGCCCCAGATCATCTTCTGTAGATCTGAGGCCG CTCACCAGGGCGTGATCACCTGGAATCCTCCACAGCGGAGCTTCCACAACTTCACCCTGTGCTACATC AAAGAAACCGAGAAGGACTGCCTGAACCTGGACAAGAACCTCATTAAGTACGACCTGCAGAACCTGAA GCCGTACACCAAATACGTGCTGAGCCTGCACGCCTACATCATTGCCAAGGTGCAGAGAAATGGCAGCG CCGCCATGTGCCACTTCACCACAAAAAGCGCCCCTCCAAGCCAAGTGTGGAACATGACCGTGTCTATG ACCAGCGACAACTCCATGCACGTGAAGTGCCGGCCTCCACGGGATAGAAATGGCCCTCACGAGAGATA CCACCTGGAAGTCGAGGCCGGAAATACCCTCGTGCGGAACGAGAGCCACAAGAACTGCGACTTCAGAG TGAAGGACCTGCAGTACAGCACCGACTACACCTTCAAGGCCTACTTCCACAATGGCGACTACCCTGGC GAGCCCTTCATCCTGCACCACAGCACCAGCTACAACAGCAAGATCCTGGACTACAGCTTCGGCGGAGG CGCCGGAAGAGATATTCCTCCACCTCTGATCGAGGAAGCCTGCGAGCTGCCTGAGTGTCAAGAGGACG CCGGCAACAAAGTGTGCAGCCTGCAGTGCAACAATCACGCCTGTGGATGGGATGGCGGCGACTGCAGC CTGAACTTCAACGACCCCTGGAAGAACTGCACCCAGTCTCTGCAGTGCTGGAAGTACTTTAGCGACGG CCACTGCGACAGCCAGTGTAATTCTGCCGGCTGCCTGTTCGACGGCTTCGATTGTCAGCGAGCCGAGG GCCAATGCAACCCTCTGTACGACCAGTACTGCAAGGACCACTTCTCCGATGGCCACTGTGACCAGGGC TGTAATAGCGCCGAGTGCGAGTGGGATGGACTGGATTGTGCCGAGCACGTGCCAGAAAGACTGGCCGC TGGAACACTGGTGGTGGTCGTTCTGATGCCTCCTGAGCAGCTGCGGAACAGCAGCTTCCACTTCCTGC GGGAACTGAGCAGAGTGCTGCACACCAACGTGGTGTTCAAGAGAGATGCCCACGGCCAGCAGATGATC TTCCCATATTACGGCAGAGAAGAGGAACTGGAACTGGACCCCATGGATGTGCGGGGCAGCATCGTGTA CCTGGAAATCGACAACCGGCAGTGCGTGCAGGCCAGCTCTCAGTGTTTTCAGAGCGCTACAGACGTGG CCGCCTTTCTGGGAGCACTGGCTTCTCTGGGCTCCCTGAACATCCCCTACAAGATCGAGGCCGTGCAG AGCGAGACAGTGGAACCTCCTCCTCCTGCTCAACTGCACTTTATGTACGTGGCCGCTGCTGCCTTCGT GCTGCTGTTCTTTGTTGGCTGCGGAGTGCTGCTGAGCAAGCGGAAGAGAAAGCACCAGCATGGCCAGC TGTGGTTCGGATCTGGATCAGGCAGCGGAAGCTCTCTGCGCGTGAAGTTCAGCAGATCAGCCGACGCT CCTGCCTATCAGCAGGGCCAGAACCAGCTGTACAACGAGCTGAACCTGGGGAGAAGAGAAGAGTACGA CGTGCTGGACAAGCGGAGAGGCAGAGATCCTGAGATGGGCGGAAAGCCCCAGCGGAGAAAGAATCCTC AAGAGGGCCTGTATAATGAGCTGCAGAAAGACAAGATGGCCGAGGCCTACAGCGAGATCGGAATGAAG GGCGAGCGCAGAAGAGGCAAGGGACACGATGGACTGTACCAGGGCCTGAGCACCGCCACCAAGGATAC CTATGATGCCCTGCACATGCAGGCCCTGCCTCCAAGAAAGCGGGGCAGAAAGAAGCTGCTGTACATCT TCAAGCAGCCCTTCATGCGGCCCGTGCAGACCACACAAGAGGAAGATGGCTGCTCCTGCAGATTCCCCAttorney Docket No. 44807-0518WO1 / P18835-01GAGGAAGAAGAAGGCGGCTGCGAACTTGGAGGCGGCGGATCTTATAGACCCGCCAGAGTGACCAGCAC CAGCCGGTTTCTGAACCCCTACGTCGTGTGCTTCATTGTGGTGGCCGGCGTTGTGATCCTGGCCGTGA CAATTGCCCTGCTGGTGTACTTCCTGGCCTTCGACCAGAAGTCCTACTTCAGCACCCTGGAAATCTCT GGCGGAGGCGGAGGATCTGGTGGCGGAGGAAGCGGTGGCGGCGGTTCTGACATCCAGATGACCCAGAC CACAAGCAGCCTGTCTGCCAGCCTGGGCGATAGAGTGACCATCAGCTGTAGAGCCAGCCAGGACATCA GCAAGTACCTGAACTGGTATCAGCAAAAGCCCGACGGCACCGTGAAGCTGCTGATCTACCACACCAGC AGACTGCACAGCGGCGTGCCAAGCAGATTTTCTGGCAGCGGCTCTGGCACCGACTACAGCCTGACAAT CAGCAACCTGGAACAAGAGGATATCGCTACCTACTTCTGCCAGCAAGGCAACACCCTGCCTTACACCT TTGGCGGAGGCACCAAGCTGGAAATCACCGGCTCTACAAGCGGCAGCGGCAAACCTGGATCTGGCGAG GGATCTACCAAGGGCGAAGTGAAACTGCAAGAGTCTGGCCCTGGACTGGTGGCCCCATCTCAGTCTCT GAGCGTGACCTGTACAGTCAGCGGAGTGTCCCTGCCTGATTACGGCGTGTCCTGGATCAGACAGCCTC CTCGGAAAGGCCTGGAATGGCTGGGAGTGATCTGGGGCAGCGAGACAACCTACTACAACAGCGCCCTG AAGTCCCGGCTGACCATCATCAAGGACAACTCCAAGAGCCAGGTGTTCCTGAAGATGAACAGCCTGCA GACCGACGACACCGCCATCTACTATTGCGCCAAGCACTACTACTACGGCGGCAGCTACGCCATGGATT ATTGGGGCCAGGGCACCAGCGTGACCGTTTCTTCTGCCGCCGCTGACTACAAGGACGACGACGACAAG CGGGCCAAACGATCTGGCTCTGGCCAGTGTACCAACTATGCCCTGCTCAAGCTCGCTGGCGACGTCGA GTCTAACCCTGGACCAATGGGAGCTGGCGCTACAGGCAGAGCTATGGATGGACCTAGACTGCTGCTGC TCCTGCTTCTGGGAGTGTCTCTTGGCGGAGCCAAAGAGGCCTGTCCTACCGGCCTGTATACACACTCT GGCGAGTGCTGCAAGGCCTGCAATCTTGGAGAAGGCGTCGCACAGCCTTGCGGCGCTAATCAGACAGT GTGCGAGCCTTGCCTGGACAGCGTGACCTTTAGCGACGTGGTGTCAGCCACCGAGCCATGCAAGCCAT GTACCGAGTGTGTGGGCCTGCAGAGCATGTCTGCCCCTTGCGTGGAAGCTGACGATGCCGTGTGTAGA TGCGCCTACGGCTACTACCAGGACGAGACAACAGGCAGATGCGAGGCCTGTAGAGTGTGCGAAGCTGG ATCTGGCCTGGTGTTCAGCTGCCAAGACAAGCAGAACACCGTGTGCGAGGAATGCCCCGATGGCACCT ATAGCGACGAGGCCAACCATGTGGATCCCTGCCTGCCTTGTACCGTGTGTGAAGATACCGAGCGGCAG CTGCGCGAGTGTACAAGATGGGCTGATGCCGAGTGCGAAGAGATCCCTGGCAGATGGATCACCAGAAG CACACCTCCAGAGGGCAGCGATAGCACAGCCCCTTCTACACAAGAGCCCGAGGCTCCTCCTGAGCAGG ACCTGATTGCTTCTACAGTGGCTGGCGTCGTGACCACCGTGATGGGATCTAGTCAGCCCGTGGTCACC AGAGGCACCACCGACAATCTGATCCCCGTGTACTGTAGCATCCTGGCCGCCGTGGTTGTTGGACTGGT GGCCTATATCGCCTTCAAGCGGTGGAACAGCTGA(SEQ ID NO: 125)MANTIS-7 DesignCD8a SP - myc tag - BB7.2 - CD45 ECD - human NOTCH1 NRR dSl- CD45 TMD - CD45 JMD -Linker 2 - CD3z Signaling - 41BB CoStim - G4S - TM1 ID JMD - TM1 ID TMD - G4Sx3 - FMC63 -FLAG tag - E2A -tNGFRAmino Acid Sequence for MANTIS-7 MALPVTALLLPLALLLHAARPEQKLISEEDLQVQLQQSGPELVKPGASVKMSCKASGYTFTSYHIQWV KQRPGQGLEWIGWIYPGDGSTQYNEKFKGKTTLTADKSSSTAYMLLSSLTSEDSAIYFCAREGTYYAM DYWGQGTSVTVSSGGGGSGGGGSGGGGSDIVMTQAPLSLPVSLGDQVSISCRSSQSIVHSNGNTYLEW YLQKPGQSPKLLIYKVSNRFSGVPDRFSGSGSGTDFTLKISRVEAEDLGVYYCFQGSHVPRT FGGGTK LELKRTQSPTPSPTGLTTAKMPSVPLSSDPLPTHTTAFSPASTFERENDFSETTTSLSPDNTSTQVSP DSLDNASAFNTTGVSSVQTPHLPTHADSQTPSAGTDTQTFSGSAANAKLNPTPGSNAISDVPGERSTA STFPTDPVSPLTTTLSLAHHSSAALPARTSNTTITANTSDAYLNASETTTLSPSGSAVISTTTIATTP SKPTCDEKYANITVDYLYNKETKLFTAKLNVNENVECGNNTCTNNEVHNLTECKNASVSISHNSCTAP DKTLILDVPPGVEKFQLHDCTQVEKADTTICLKWKNIETFTCDTQNITYRFQCGNMIFDNKEIKLENL EPEHEYKCDSEILYNNHKFTNASKIIKTDFGSPGEPQIIFCRSEAAHQGVITWNPPQRSFHNFTLCYIAttorney Docket No. 44807-0518WO1 / P18835-01KETEKDCLNLDKNLIKYDLQNLKPYTKYVLSLHAYIIAKVQRNGSAAMCHFTTKSAPPSQVWNMTVSM TSDNSMHVKCRPPRDRNGPHERYHLEVEAGNTLVRNESHKNCDFRVKDLQYSTDYTFKAYFHNGDYPG EPFILHHSTSYNSKILDYSFGGGAGRDIPPPLIEEACELPECQEDAGNKVCSLQCNNHACGWDGGDCS LNFNDPWKNCTQSLQCWKYFSDGHCDSQCNSAGCLFDGFDCQRAEGQCNPLYDQYCKDHFSDGHCDQG CNSAECEWDGLDCAEHVPERLAAGTLVVVVLMPPEQLRNSSFHFLRELSRVLHTNVVFKRDAHGQQMI FPYYGREEELELDPMDVRGSIVYLEIDNRQCVQASSQCFQSATDVAAFLGALASLGSLNIPYKIEAVQ SETVEPPPPAQLHALIAFLAFLIIVTSI LLVVLYKIYDLHKKRGSGSGSGSSLRVKFSRSADAPAYQ QGQNQLYNELNLGRREEYDVLDKRRGRDPEMGGKPQRRKNPQEGLYNELQKDKMAEAYSEIGMKGERR RGKGHDGLYQGLSTATKDTYDALHMQALPPRKRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEE GGCELGGGGSYRPARVTSTSRFLNPYVVCFIVVAGVVILAVTIALLVYFLAFDQKSYFSTLEISGGGG GSGGGGSGGGGSDIQMTQTTSSLSASLGDRVTISCRASQDISKYLNWYQQKPDGTVKLLIYHTSRLHS GVPSRFSGSGSGTDYSLTISNLEQEDIATYFCQQGNTLPYTFGGGTKLEITGSTSGSGKPGSGEGSTK GEVKLQESGPGLVAPSQSLSVTCTVSGVSLPDYGVSWIRQPPRKGLEWLGVIWGSETTYYNSALKSRL TI IKDNSKSQVFLKMNSLQTDDTAIYYCAKHYYYGGSYAMDYWGQGTSVTVSSAAADYKDDDDKRAKR SGSGQCTNYALLKLAGDVESNPGPMGAGATGRAMDGPRLLLLLLLGVSLGGAKEACPTGLYTHSGECC KACNLGEGVAQPCGANQTVCEPCLDSVTFSDVVSATEPCKPCTECVGLQSMSAPCVEADDAVCRCAYG YYQDETTGRCEACRVCEAGSGLVFSCQDKQNTVCEECPDGTYSDEANHVDPCLPCTVCEDTERQLREC TRWADAECEEIPGRWITRSTPPEGSDSTAPSTQEPEAPPEQDLIASTVAGVVTTVMGSSQPVVTRGTTNucleic Acid Sequence for MANTIS-7 ATGGCTCTGCCTGTGACAGCTCTGCTGCTGCCTCTGGCTCTGCTTCTGCATGCCGCTAGACCTGAGCA GAAGCTGATCTCCGAAGAGGACCTGCAGGTTCAGCTGCAGCAGTCTGGACCTGAGCTGGTTAAGCCTG GCGCTTCCGTGAAGATGAGCTGCAAGGCCAGCGGCTACACCTTCACCAGCTACCACATCCAGTGGGTC AAGCAGAGGCCTGGACAGGGACTCGAGTGGATCGGCTGGATCTATCCTGGCGACGGCAGCACCCAGTA CAACGAGAAGTTCAAGGGCAAGACCACACTGACCGCCGACAAGAGCAGCAGCACAGCCTACATGCTGC TGAGCAGCCTGACCAGCGAGGACAGCGCCATCTACTTTTGTGCCAGAGAGGGCACCTACTACGCCATG GATTATTGGGGCCAGGGCACCAGCGTGACAGTCTCTTCTGGTGGCGGAGGATCTGGCGGAGGTGGAAG CGGCGGAGGCGGATCTGATATCGTGATGACACAGGCCCCTCTGAGCCTGCCTGTGTCTCTGGGAGATC AGGTGTCCATCAGCTGTCGGAGCAGCCAGAGCATCGTGCACAGCAACGGCAACACCTACCTGGAATGG TATCTGCAGAAGCCCGGACAGAGCCCCAAGCTGCTGATCTACAAGGTGTCCAACCGGTTCAGCGGCGT GCCCGATAGATTTTCTGGCTCTGGCAGCGGCACCGACTTCACCCTGAAGATCTCTAGAGTGGAAGCCG AGGACCTGGGCGTGTACTACTGCTTCCAAGGCAGCCACGTGCCAAGAACCTTTGGCGGCGGAACAAAG CTGGAACTGAAGCGGACACAGAGCCCCACACCATCTCCAACAGGACTGACCACCGCCAAGATGCCTAG CGTGCCCCTCTCTTCTGACCCTCTGCCTACACACACCACCGCTTTTAGCCCTGCCAGCACCTTCGAGA GAGAGAACGACTTCAGCGAGACAACCACCTCTCTGAGCCCCGACAACACCAGCACACAGGTGTCCCCA GACAGCCTGGATAATGCCAGCGCCTTCAATACCACCGGCGTGTCCTCTGTGCAGACCCCTCATCTGCC AACACACGCCGATAGCCAGACACCTTCTGCCGGCACCGATACACAGACCTTTTCTGGCTCTGCCGCCA ACGCCAAGCTGAACCCTACACCTGGCAGCAACGCCATCTCTGATGTGCCTGGCGAGAGAAGCACCGCC AGCACATTTCCAACAGACCCCGTGTCTCCCCTGACCACCACACTGTCTCTGGCCCACCATAGCTCTGC TGCCCTGCCTGCCAGAACCAGCAACACCACCATCACCGCCAATACCAGCGACGCCTACCTGAACGCCA GCGAAACCACAACACTGAGCCCTAGCGGAAGCGCCGTGATCAGCACAACCACAATCGCCACCACACCT AGCAAGCCTACCTGCGACGAGAAGTACGCCAACATCACCGTGGACTACCTGTACAACAAAGAGACAAA GCTGTTCACGGCCAAGCTCAACGTGAACGAGAACGTGGAATGCGGCAACAATACCTGCACCAACAACG AGGTGCACAACCTGACCGAGTGCAAGAACGCCTCCGTGTCCATCAGCCACAACAGCTGCACAGCCCCT GACAAGACCCTGATCCTGGATGTGCCTCCTGGCGTGGAAAAGTTCCAGCTGCACGATTGCACCCAGGT GGAAAAGGCCGATACCACCATCTGCCTGAAGTGGAAGAACATCGAGACATTCACCTGTGACACCCAGAAttorney Docket No. 44807-0518WO1 / P18835-01ACATCACCTACCGGTTCCAGTGCGGCAATATGATCTTCGATAACAAAGAAATCAAGCTCGAGAACCTC GAGCCTGAGCACGAGTACAAGTGCGACAGCGAGATCCTGTATAACAATCACAAGTTCACCAACGCCAG CAAGATCATCAAGACCGACTTCGGCTCTCCCGGCGAGCCCCAGATCATCTTCTGTAGATCTGAGGCCG CTCACCAGGGCGTGATCACCTGGAATCCTCCACAGCGGAGCTTCCACAACTTCACCCTGTGCTACATC AAAGAAACCGAGAAGGACTGCCTGAACCTGGACAAGAACCTCATTAAGTACGACCTGCAGAACCTGAA GCCGTACACCAAATACGTGCTGAGCCTGCACGCCTACATCATTGCCAAGGTGCAGAGAAATGGCAGCG CCGCCATGTGCCACTTCACCACAAAAAGCGCCCCTCCAAGCCAAGTGTGGAACATGACCGTGTCTATG ACCAGCGACAACTCCATGCACGTGAAGTGCCGGCCTCCACGGGATAGAAATGGCCCTCACGAGAGATA CCACCTGGAAGTCGAGGCCGGAAATACCCTCGTGCGGAACGAGAGCCACAAGAACTGCGACTTCAGAG TGAAGGACCTGCAGTACAGCACCGACTACACCTTCAAGGCCTACTTCCACAATGGCGACTACCCTGGC GAGCCCTTCATCCTGCACCACAGCACCAGCTACAACAGCAAGATCCTGGACTACAGCTTCGGCGGAGG CGCCGGAAGAGATATTCCTCCACCTCTGATCGAGGAAGCCTGCGAGCTGCCTGAGTGTCAAGAGGACG CCGGCAACAAAGTGTGCAGCCTGCAGTGCAACAATCACGCCTGTGGATGGGATGGCGGCGACTGCAGC CTGAACTTCAACGACCCCTGGAAGAACTGCACCCAGTCTCTGCAGTGCTGGAAGTACTTTAGCGACGG CCACTGCGACAGCCAGTGTAATTCTGCCGGCTGCCTGTTCGACGGCTTCGATTGTCAGCGAGCCGAGG GCCAATGCAACCCTCTGTACGACCAGTACTGCAAGGACCACTTCTCCGATGGCCACTGTGACCAGGGC TGTAATAGCGCCGAGTGCGAGTGGGATGGACTGGATTGTGCCGAGCACGTGCCAGAAAGACTGGCCGC TGGAACACTGGTGGTGGTCGTTCTGATGCCTCCTGAGCAGCTGCGGAACAGCAGCTTCCACTTCCTGC GGGAACTGAGCAGAGTGCTGCACACCAACGTGGTGTTCAAGAGAGATGCCCACGGCCAGCAGATGATC TTCCCATATTACGGCAGAGAAGAGGAACTGGAACTGGACCCCATGGATGTGCGGGGCAGCATCGTGTA CCTGGAAATCGACAACCGGCAGTGCGTGCAGGCCAGCTCTCAGTGTTTTCAGAGCGCTACAGACGTGG CCGCCTTTCTGGGAGCACTGGCTTCTCTGGGCTCCCTGAACATCCCCTACAAGATCGAGGCCGTGCAG AGCGAGACAGTGGAACCTCCTCCTCCTGCTCAACTGCACGCACTTATCGCGTTCCTCGCGTTTCTCAT TATTGTTACATCCATAGCTTTGCTTGTTGTACTTTACAAGATTTATGACCTTCATAAGAAACGAGGAT CTGGATCAGGCAGCGGAAGCTCTCTGCGCGTGAAGTTCAGCAGATCAGCCGACGCTCCTGCCTATCAG CAGGGCCAGAACCAGCTGTACAACGAGCTGAACCTGGGGAGAAGAGAAGAGTACGACGTGCTGGACAA GCGGAGAGGCAGAGATCCTGAGATGGGCGGAAAGCCCCAGCGGAGAAAGAATCCTCAAGAGGGCCTGT ATAATGAGCTGCAGAAAGACAAGATGGCCGAGGCCTACAGCGAGATCGGAATGAAGGGCGAGCGCAGA AGAGGCAAGGGACACGATGGACTGTACCAGGGCCTGAGCACCGCCACCAAGGATACCTATGATGCCCT GCACATGCAGGCCCTGCCTCCAAGAAAGCGGGGCAGAAAGAAGCTGCTGTACATCTTCAAGCAGCCCT TCATGCGGCCCGTGCAGACCACACAAGAGGAAGATGGCTGCTCCTGCAGATTCCCCGAGGAAGAAGAA GGCGGCTGCGAACTTGGAGGCGGCGGATCTTATAGACCCGCCAGAGTGACCAGCACCAGCCGGTTTCT GAACCCCTACGTCGTGTGCTTCATTGTGGTGGCCGGCGTTGTGATCCTGGCCGTGACAATTGCCCTGC TGGTGTACTTCCTGGCCTTCGACCAGAAGTCCTACTTCAGCACCCTGGAAATCTCTGGCGGAGGCGGA GGATCTGGTGGCGGAGGAAGCGGTGGCGGCGGTTCTGACATCCAGATGACCCAGACCACAAGCAGCCT GTCTGCCAGCCTGGGCGATAGAGTGACCATCAGCTGTAGAGCCAGCCAGGACATCAGCAAGTACCTGA ACTGGTATCAGCAAAAGCCCGACGGCACCGTGAAGCTGCTGATCTACCACACCAGCAGACTGCACAGC GGCGTGCCAAGCAGATTTTCTGGCAGCGGCTCTGGCACCGACTACAGCCTGACAATCAGCAACCTGGA ACAAGAGGATATCGCTACCTACTTCTGCCAGCAAGGCAACACCCTGCCTTACACCTTTGGCGGAGGCA CCAAGCTGGAAATCACCGGCTCTACAAGCGGCAGCGGCAAACCTGGATCTGGCGAGGGATCTACCAAG GGCGAAGTGAAACTGCAAGAGTCTGGCCCTGGACTGGTGGCCCCATCTCAGTCTCTGAGCGTGACCTG TACAGTCAGCGGAGTGTCCCTGCCTGATTACGGCGTGTCCTGGATCAGACAGCCTCCTCGGAAAGGCC TGGAATGGCTGGGAGTGATCTGGGGCAGCGAGACAACCTACTACAACAGCGCCCTGAAGTCCCGGCTG ACCATCATCAAGGACAACTCCAAGAGCCAGGTGTTCCTGAAGATGAACAGCCTGCAGACCGACGACAC CGCCATCTACTATTGCGCCAAGCACTACTACTACGGCGGCAGCTACGCCATGGATTATTGGGGCCAGG GCACCAGCGTGACCGTTTCTTCTGCCGCCGCTGACTACAAGGACGACGACGACAAGCGGGCCAAACGA TCTGGCTCTGGCCAGTGTACCAACTATGCCCTGCTCAAGCTCGCTGGCGACGTCGAGTCTAACCCTGG ACCAATGGGAGCTGGCGCTACAGGCAGAGCTATGGATGGACCTAGACTGCTGCTGCTCCTGCTTCTGG GAGTGTCTCTTGGCGGAGCCAAAGAGGCCTGTCCTACCGGCCTGTATACACACTCTGGCGAGTGCTGCAttorney Docket No. 44807-0518WO1 / P18835-01AAGGCCTGCAATCTTGGAGAAGGCGTCGCACAGCCTTGCGGCGCTAATCAGACAGTGTGCGAGCCTTG CCTGGACAGCGTGACCTTTAGCGACGTGGTGTCAGCCACCGAGCCATGCAAGCCATGTACCGAGTGTG TGGGCCTGCAGAGCATGTCTGCCCCTTGCGTGGAAGCTGACGATGCCGTGTGTAGATGCGCCTACGGC TACTACCAGGACGAGACAACAGGCAGATGCGAGGCCTGTAGAGTGTGCGAAGCTGGATCTGGCCTGGT GTTCAGCTGCCAAGACAAGCAGAACACCGTGTGCGAGGAATGCCCCGATGGCACCTATAGCGACGAGG CCAACCATGTGGATCCCTGCCTGCCTTGTACCGTGTGTGAAGATACCGAGCGGCAGCTGCGCGAGTGT ACAAGATGGGCTGATGCCGAGTGCGAAGAGATCCCTGGCAGATGGATCACCAGAAGCACACCTCCAGA GGGCAGCGATAGCACAGCCCCTTCTACACAAGAGCCCGAGGCTCCTCCTGAGCAGGACCTGATTGCTT CTACAGTGGCTGGCGTCGTGACCACCGTGATGGGATCTAGTCAGCCCGTGGTCACCAGAGGCACCACC GACAATCTGATCCCCGTGTACTGTAGCATCCTGGCCGCCGTGGTTGTTGGACTGGTGGCCTATATCGC CTTCAAGCGGTGGAACAGCTGA(SEQ ID NO: 126)MANTIS-8 DesignCD8a SP - myc tag - BB7.2 - CD45 ECD - sNRR - NOTCH1 TMD - NOTCH2 JMD - RAM7 -Linker 2 - CD3z Signaling - 41BB CoStim - G4S - TM1 ID JMD - TM1 ID TMD - G4Sx3 - FMC63 -FLAG tag - E2A - tNGFRAmino Acid Sequence for MANTIS-8 MALPVTALLLPLALLLHAARPEQKLISEEDLQVQLQQSGPELVKPGASVKMSCKASGYTFTSYHIQWV KQRPGQGLEWIGWIYPGDGSTQYNEKFKGKTTLTADKSSSTAYMLLSSLTSEDSAIYFCAREGTYYAM DYWGQGTSVTVSSGGGGSGGGGSGGGGSDIVMTQAPLSLPVSLGDQVSISCRSSQSIVHSNGNTYLEW YLQKPGQSPKLLIYKVSNRFSGVPDRFSGSGSGTDFTLKISRVEAEDLGVYYCFQGSHVPRT FGGGTK LELKRTQSPTPSPTGLTTAKMPSVPLSSDPLPTHTTAFSPASTFERENDFSETTTSLSPDNTSTQVSP DSLDNASAFNTTGVSSVQTPHLPTHADSQTPSAGTDTQTFSGSAANAKLNPTPGSNAISDVPGERSTA STFPTDPVSPLTTTLSLAHHSSAALPARTSNTTITANTSDAYLNASETTTLSPSGSAVISTTTIATTP SKPTCDEKYANITVDYLYNKETKLFTAKLNVNENVECGNNTCTNNEVHNLTECKNASVSISHNSCTAP DKTLILDVPPGVEKFQLHDCTQVEKADTTICLKWKNIETFTCDTQNITYRFQCGNMIFDNKEIKLENL EPEHEYKCDSEILYNNHKFTNASKIIKTDFGSPGEPQIIFCRSEAAHQGVITWNPPQRSFHNFTLCYI KETEKDCLNLDKNLIKYDLQNLKPYTKYVLSLHAYIIAKVQRNGSAAMCHFTTKSAPPSQVWNMTVSM TSDNSMHVKCRPPRDRNGPHERYHLEVEAGNTLVRNESHKNCDFRVKDLQYSTDYTFKAYFHNGDYPG EPFILHHSTSYNSKEVQLVESGGGLVQPGGSLRLSCAASGFTFSSYWIHWVRQAPGKGLEWVARINPP NRSNQYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGSGFRWVMDYWGQGTLVTVSSGGS SRSSSSGGGGSGGGGDIQMTQSPSSLSASVGDRVTITCRASQDVSTAVAWYQQKPGKAPKLLIYSASF LYSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQFYTTPSTFGQGTKVEIKGGGSEQKLISEEDL GGGSILDYSFGGGAGRDIPPPLIEEACELPECQEDAGNKVCSLQCNNHACGWDGGDCSLNFNDPWKNC TQSLQCWKYFSDGHCDSQCNSAGCLFDGFDCQRAEGQCNPLYDQYCKDHFSDGHCDQGCNSAECEWDG LDCAEHVPERLAAGTLVVVVLMPPEQLRNSSFHFLRELSRVLHTNVVFKRDAHGQQMI FPYYGREEEL ELDPMDVRGSIVYLEIDNRQCVQASSQCFQSATDVAAFLGALASLGSLNIPYKIEAVQSETVEPPPPA QLHFMYVAAAAFVLLFFVGCGVLLSKRKRKHQHGQLWFGSGSGSGSSLRVKFSRSADAPAYQQGQNQL YNELNLGRREEYDVLDKRRGRDPEMGGKPQRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHD GLYQGLSTATKDTYDALHMQALPPRKRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCELG GGGSYRPARVTSTSRFLNPYVVCFIVVAGVVILAVTIALLVY FLAFDQKSYFSTLEISGGGGGSGGGG SGGGGSDIQMTQTTSSLSASLGDRVTISCRASQDISKYLNWYQQKPDGTVKLLIYHTSRLHSGVPSRF SGSGSGTDYSLTISNLEQEDIATYFCQQGNTLPYTFGGGTKLEITGSTSGSGKPGSGEGSTKGEVKLQ ESGPGLVAPSQSLSVTCTVSGVSLPDYGVSWIRQPPRKGLEWLGVIWGSETTYYNSALKSRLTIIKDN SKSQVFLKMNSLQTDDTAIYYCAKHYYYGGSYAMDYWGQGTSVTVSSAAADYKDDDDKRAKRSGSGQCAttorney Docket No. 44807-0518WO1 / P18835-01TNYALLKLAGDVESNPGPMGAGATGRAMDGPRLLLLLLLGVSLGGAKEACPTGLYTHSGECCKACNLG EGVAQPCGANQTVCEPCLDSVTFSDVVSATEPCKPCTECVGLQSMSAPCVEADDAVCRCAYGYYQDET TGRCEACRVCEAGSGLVFSCQDKQNTVCEECPDGTYSDEANHVDPCLPCTVCEDTERQLRECTRWADA ECEEIPGRWITRSTPPEGSDSTAPSTQEPEAPPEQDLIASTVAGVVTTVMGSSQPVVTRGTTDNLIPV YCSILAAVVVGLVAYIAFKRWNS*(SEQ ID NO:11)Nucleic Acid Sequence for MANTIS-8 ATGGCTCTGCCTGTGACAGCTCTGCTGCTGCCTCTGGCTCTGCTTCTGCATGCCGCTAGACCTGAGCA GAAGCTGATCTCCGAAGAGGACCTGCAGGTTCAGCTGCAGCAGTCTGGACCTGAGCTGGTTAAGCCTG GCGCTTCCGTGAAGATGAGCTGCAAGGCCAGCGGCTACACCTTCACCAGCTACCACATCCAGTGGGTC AAGCAGAGGCCTGGACAGGGACTCGAGTGGATCGGCTGGATCTATCCTGGCGACGGCAGCACCCAGTA CAACGAGAAGTTCAAGGGCAAGACCACACTGACCGCCGACAAGAGCAGCAGCACAGCCTACATGCTGC TGAGCAGCCTGACCAGCGAGGACAGCGCCATCTACTTTTGTGCCAGAGAGGGCACCTACTACGCCATG GATTATTGGGGCCAGGGCACCAGCGTGACAGTCTCTTCTGGTGGCGGAGGATCTGGCGGAGGTGGAAG CGGCGGAGGCGGATCTGATATCGTGATGACACAGGCCCCTCTGAGCCTGCCTGTGTCTCTGGGAGATC AGGTGTCCATCAGCTGTCGGAGCAGCCAGAGCATCGTGCACAGCAACGGCAACACCTACCTGGAATGG TATCTGCAGAAGCCCGGACAGAGCCCCAAGCTGCTGATCTACAAGGTGTCCAACCGGTTCAGCGGCGT GCCCGATAGATTTTCTGGCTCTGGCAGCGGCACCGACTTCACCCTGAAGATCTCTAGAGTGGAAGCCG AGGACCTGGGCGTGTACTACTGCTTCCAAGGCAGCCACGTGCCAAGAACCTTTGGCGGCGGAACAAAG CTGGAACTGAAGCGGACACAGAGCCCCACACCATCTCCAACAGGACTGACCACCGCCAAGATGCCTAG CGTGCCCCTCTCTTCTGACCCTCTGCCTACACACACCACCGCTTTTAGCCCTGCCAGCACCTTCGAGA GAGAGAACGACTTCAGCGAGACAACCACCTCTCTGAGCCCCGACAACACCAGCACACAGGTGTCCCCA GACAGCCTGGATAATGCCAGCGCCTTCAATACCACCGGCGTGTCCTCTGTGCAGACCCCTCATCTGCC AACACACGCCGATAGCCAGACACCTTCTGCCGGCACCGATACACAGACCTTTTCTGGCTCTGCCGCCA ACGCCAAGCTGAACCCTACACCTGGCAGCAACGCCATCTCTGATGTGCCTGGCGAGAGAAGCACCGCC AGCACATTTCCAACAGACCCCGTGTCTCCCCTGACCACCACACTGTCTCTGGCCCACCATAGCTCTGC TGCCCTGCCTGCCAGAACCAGCAACACCACCATCACCGCCAATACCAGCGACGCCTACCTGAACGCCA GCGAAACCACAACACTGAGCCCTAGCGGAAGCGCCGTGATCAGCACAACCACAATCGCCACCACACCT AGCAAGCCTACCTGCGACGAGAAGTACGCCAACATCACCGTGGACTACCTGTACAACAAAGAGACAAA GCTGTTCACGGCCAAGCTCAACGTGAACGAGAACGTGGAATGCGGCAACAATACCTGCACCAACAACG AGGTGCACAACCTGACCGAGTGCAAGAACGCCTCCGTGTCCATCAGCCACAACAGCTGCACAGCCCCT GACAAGACCCTGATCCTGGATGTGCCTCCTGGCGTGGAAAAGTTCCAGCTGCACGATTGCACCCAGGT GGAAAAGGCCGATACCACCATCTGCCTGAAGTGGAAGAACATCGAGACATTCACCTGTGACACCCAGA ACATCACCTACCGGTTCCAGTGCGGCAATATGATCTTCGATAACAAAGAAATCAAGCTCGAGAACCTC GAGCCTGAGCACGAGTACAAGTGCGACAGCGAGATCCTGTATAACAATCACAAGTTCACCAACGCCAG CAAGATCATCAAGACCGACTTCGGCTCTCCCGGCGAGCCCCAGATCATCTTCTGTAGATCTGAGGCCG CTCACCAGGGCGTGATCACCTGGAATCCTCCACAGCGGAGCTTCCACAACTTCACCCTGTGCTACATC AAAGAAACCGAGAAGGACTGCCTGAACCTGGACAAGAACCTCATTAAGTACGACCTGCAGAACCTGAA GCCGTACACCAAATACGTGCTGAGCCTGCACGCCTACATCATTGCCAAGGTGCAGAGAAATGGCAGCG CCGCCATGTGCCACTTCACCACAAAAAGCGCCCCTCCAAGCCAAGTGTGGAACATGACCGTGTCTATG ACCAGCGACAACTCCATGCACGTGAAGTGCCGGCCTCCACGGGATAGAAATGGCCCTCACGAGAGATA CCACCTGGAAGTCGAGGCCGGAAATACCCTCGTGCGGAACGAGAGCCACAAGAACTGCGACTTCAGAG TGAAGGACCTGCAGTACAGCACCGACTACACCTTCAAGGCCTACTTCCACAATGGCGACTACCCTGGC GAGCCCTTCATCCTGCACCACAGCACCAGCTACAACAGCAAGGAGGTGCAGCTGGTTGAATCTGGCGG AGGACTGGTTCAGCCTGGCGGATCTCTGAGACTGTCTTGTGCCGCCAGCGGCTTCACCTTCAGCAGCT ATTGGATCCACTGGGTCCGACAGGCCCCTGGCAAAGGACTTGAATGGGTCGCCAGGATCAACCCTCCT AACAGAAGCAACCAGTACGCCGACAGCGTGAAGGGCAGATTCACCATCAGCGCCGACACCAGCAAG...

Claims

Attorney Docket No. 44807-0518WO1 / P18835-01WHAT IS CLAIMED IS:

1. A logic-gated receptor comprising, from N-terminus to C-terminus:(a) an antigen-triggered proteolysis receptor (ATPR) comprising: (a-i) a first antigen binding domain, (a-ii) a large extracellular domain, and (a-iii) a type I transmembrane domain comprising a juxtamembrane domain; and(b) a chimeric antigen receptor (CAR) comprising: (b-i) one or more signaling domains, (b-ii) a type II transmembrane domain, and (b-iii) a second antigen binding domain.

2. The logic-gated receptor of claim 1, wherein the large extracellular domain is derived from CD45 (PTPRC), CD43, CEACAM5, N0TCH1, N0TCH2, N0TCH3, N0TCH4, PTPRB, PTPRD, PTPRF, PTPRG PTPRH, PTPRJ (CD 148), PTPRK, PTPRM, PTPRN, PTPRN1, PTPRO, PTPRQ, PTPRS, PTPRT, PTPRU, PTPRZ, and PTPRZ1, CD21, CD35, CD55, CD97, CD91, thrombomodulin, JAG1, JAG2, DLK1, DLL1, DLL3, orDLL4.

3. The logic-gated receptor of any one of claims 1-2, wherein said large extracellular domain blocks binding of said second antigen binding domain to its target antigen.

4. The logic-gated receptor of any one of claims 1-3, wherein the large extracellular domain comprises a proteolysis site.

5. The logic-gated receptor of claim 4, wherein the proteolysis site is a cryptic proteolysis site.

6. The logic-gated receptor of any one of claims 1-5, wherein said type I transmembrane domain comprises said juxtamembrane domain is a CD45 transmembrane comprising a CD45 juxtamembrane domain.

7. The logic-gated receptor of any one of claims 1-6, wherein said first antigen binding domain and said second antigen binding domain are each independently an antigen-bindingAttorney Docket No. 44807-0518WO1 / P18835-01fragment (Fab), a variable region of an antibody heavy chain, a variable region of a light chain, a single-domain antibody, a single chain variable fragment (scFv), an antibody, an antibody-based recognition scaffold, a non-antibody -based recognition scaffold, a receptor ligand, a receptor, a target of a non-antibody-based recognition scaffold, an extracellular matrix component, or an adhesion molecule.

8. The logic-gated receptor of any one of claims 1-7, wherein said first antigen binding domain and said second antigen binding domain target different antigens.

9. The logic-gated receptor of any one of claims 1-7, wherein said first antigen binding domain and second antigen binding domain target the same antigen.

10. The logic-gated receptor of any one of claims 1-8, wherein said ATPR comprises, consists essentially of, or consists of the amino acid set forth in any one of SEQ ID NOs:4-19 or SEQ ID NOs: 136-140.

11. The logic-gated receptor of any one of claims 1-8, wherein said CAR further comprises an accessory signaling module.

12. A nucleic acid construct comprising a nucleotide sequence encoding the logic-gated receptor of any one of claims 1-11.

13. The nucleic acid construct of claim 12, wherein said nucleic acid construct is an expression vector.

14. A cell comprising a nucleic acid construct of any one of claims 12-13, wherein said cell expresses said logic-gated receptor.

15. A cell comprising a logic-gated receptor of any one of claims 1-11.Attorney Docket No. 44807-0518WO1 / P18835-0116. The cell of any one of claims 14-15, wherein said cell is a T cell, a B cell, a monocyte, a dendiritic cell, a macrophage, a stem cell, or an NK cell.

17. A method of treating a mammal having a disease, disorder, or condition characterized by a cell-surface antigen, wherein said method comprises administering, to said mammal, a composition comprising a cell of any one of claims 14-16, wherein at least one of said first antigen binding domain and said second antigen binding domain target said cell-surface antigen.

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

19. The method of any one of claims 17-18, wherein said large extracellular domain inhibits binding of said second antigen binding domain to its target antigen.

20. The method of claim 19, wherein said inhibition is a steric inhibition.

21. The method of any one of claims 17-20, wherein binding of said first antigen binding domain to its target antigen releases said ATPR from the logic-gated receptor, thus leaving said CAR available to bind its target antigen.

22. The method of claim 21, wherein said CAR, when bound to its target antigen, activates the cell.

23. The method of any one of claims 17-22, wherein said disease is cancer.

24. The method of claim 23, wherein said cancer is selected from the group consisting of an acute lymphoblastic leukemia (ALL), an acute myeloid leukemia (AML), a T cell leukemia, an anal cancer, an astrocytoma, a tetroid / rhabdoid tumor, a skin cancer, a biliary cancer, an osteosarcoma, a breast cancer, a central nervous system (CNS) cancer, a cervical cancer, a colorectal cancer, a T cell lymphoma, a diffuse intrinsic pontine glioma (DIPG), anAttorney Docket No. 44807-0518WO1 / P18835-01endometrial cancer, an esophageal cancer, a ewing sarcoma, a retinablastoma, a gastric cancer, a head and neck cancer, a renal cancer, a liver cancer, a lung cancer, a neuroblastoma, a lung cancer, an oral cancer, an ovarian cancer, a pancreatic cancer, a rectal cancer, a small cell lung cancer (SCLC), a non-small cell lung cancer (NSCLC), a testicular cancer, and a thyroid cancer.

25. The method of any one of claims 23-24, wherein the number of cancer cells within said mammal is reduced following said administering step.

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