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Weight Change ) ( (51) International Patent Classification: (74) Agent: ELRIFI, Ivor R. et al.; COOLEY LLP, 1299 Penn¬ C07K 14/705 (2006.01) A61K 35/1 7 (2015.01) sylvania Avenue, NW, Suite 700, Washington, District of C07K 16/28 (2006.01) C07K 14/725 (2006.01) Columbia 20004 (US). C12N 15/62 (2006.01) (81) Designated States (unless otherwise indicated, for every (21) International Application Number: kind of national protection av ailable) . AE, AG, AL, AM, PCT/US20 18/066936 AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DJ, DK, DM, DO, (22) International Filing Date: DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, 20 December 2018 (20. 12.2018) HR, HU, ID, IL, IN, IR, IS, JO, JP, KE, KG, KH, KN, KP, (25) Filing Language: English KR, KW, KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, (26) Publication Language: English OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, (30) Priority Data: SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, 62/608,571 20 December 2017 (20. 12.2017) US TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. 62/608,894 2 1 December 2017 (21. 12.2017) US (84) Designated States (unless otherwise indicated, for every (71) Applicant: POSEIDA THERAPEUTICS, INC. kind of regional protection available) . ARIPO (BW, GH, [US/US]; 4242 Campus Point Court, Suite 700, San Diego, GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ, TZ, California 92121 (US). UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, TJ, TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, DK, (72) Inventors: OSTERTAG, Eric; 4242 CAMPUS POINT EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, LV, COURT, SUITE 700, San Diego, California 92121 (US). MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, SM, SHEDLOCK, Devon; 4242 Campus Point Court, Suite TR), OAPI (BF, BJ, CF, CG, Cl, CM, GA, GN, GQ, GW, 700, San Diego, California 92121 (US). KM, ML, MR, NE, SN, TD, TG). (54) Title: VCAR COMPOSITIONS AND METHODS FOR USE FIGURE 1 Weight Change -404 Days Post-Treatment (57) Abstract: Disclosed are VHH chimeric antigen receptors (VCARs), VCAR transposons encoding VCARs of the disclosure, cells modified to express VCARs of the disclosure, as well as methods of making and methods of using the same for adoptive cell therapy. [Continued on nextpage] ||| ||||| ||||| ||||| |||| 11| ||| ||||| ||||| ||||| ||||| ||||| |||| limn nil nil nil Declarations under Rule 4.17: as to applicant's entitlement to apply for and be granted a patent (Rule 4.17(H)) Published: with international search report (Art. 21(3)) before the expiration of the time limit for amending the claims and to be republished in the event of receipt of amendments (Rule 48.2(h)) with sequence listing part of description (Rule 5.2(a)) VCAR COMPOSITIONS AND METHODS FOR USE RELATED APPLICATIONS [01] This application claims the benefit of provisional applications USSN 62/608,571, filed December 20, 2017 and USSN 62/608,894, filed December 21, 2017, the contents of each of which are herein incorporated by reference in their entirety. FIELD OF THE DISCLOSURE [02] The disclosure is directed to molecular biology, and more, specifically, to chimeric antigen receptors, and to transposons containing one or more VCARs, as well as methods of making and using the same. INCORPORATION-BY-REFERENCE OF SEQUENCE LISTING [03] The contents of the file named “POTH-034_OOlWO_SeqListing_ST25_R.txt”, which was created on December 19, 2018, and is 54.4 MB in size are hereby incorporated by reference in their entirety. BACKGROUND [04] There has been a long-felt but unmet need in the art for a method of directing the specificity of an immune cell without using traditional antibody sequences or fragments thereof. The disclosure provides a superior chimeric antigen receptor. SUMMARY [05] The disclosure provides a chimeric antigen receptor (CAR) comprising: (a) an ectodomain comprising an antigen recognition region, wherein the antigen recognition region comprises at least one single domain antibody; (b) a transmembrane domain, and (c) an endodomain comprising at least one costimulatory domain. In some embodiments, the single domain antibody comprises a human or humanized sequence. In some embodiments, the single domain antibody comprises a non-naturally occurring sequence. In some embodiments, the single domain antibody comprises a recombinant or chimeric sequence. In some embodiments, the single domain antibody comprises a VHH or a sequence encoding a VHH. In some embodiments, the single domain antibody comprises a VH or a sequence encoding a VH. In some embodiments, the single domain antibody comprises a VH of the disclosure or a sequence encoding a VH of the disclosure. [06] The disclosure provides a chimeric antigen receptor (CAR) comprising: (a) an ectodomain comprising an antigen recognition region, wherein the antigen recognition region comprises at least one VHH; (b) a transmembrane domain, and (c) an endodomain comprising at least one costimulatory domain. As used throughout the disclosure, a CAR comprising a VHH is referred to as a VCAR. In certain embodiments, the antigen recognition region may comprise two VHHs to produce a bi-specific or tandem VCAR. In certain embodiments, the antigen recognition region may comprise three VHHs to produce a tri-specific VCAR. [07] In certain embodiments of the VCARs of the disclosure, the ectodomain may further comprise a signal peptide. Alternatively, or in addition, in certain embodiments, the ectodomain may further comprise a hinge between the antigen recognition region and the transmembrane domain. In certain embodiments, the ectodomain may further comprise a signal peptide. Alternatively, or in addition, in certain embodiments, the ectodomain may further comprise a hinge between the antigen recognition region and the transmembrane domain. [08] In certain embodiments of the VCARs of the disclosure, the VHH comprises or consists of the amino acid sequence malpvtalllplalllhaarpevqllesggglvqpggslrlscaasgftfssyamnwvrqapgkglewvagiigsggstyyadsvkgrfsi srdnskntldlqmnslraedtavyycvkdwnttmitergqgtlvtvsstttpaprpptpaptiasqplslrpeacrpaaggavhtrgldfac diyiwaplagtcgvlllslvitlyckrgrkkllyifkqpfmrpvqttqeedgcscrfpeeeeggcelrvkfsrsadapaykqgqnqlynel nlgrreeydvldkrrgrdpemggkprrknpqeglynelqkdkmaeayseigmkgerrrgkghdglyqglstatkdtydalhmqalp pr (VH-A; SEQ ID NO: 18000) or the VHH comprises or consists of the nucleic acid sequence atggctctgcctgtgacagctctgctgctgcctctggctctgcttcttcatgcggcgcgccctgaagttcagctgcttgaatctggcggaggc ctggttcaacctggcggatctctgagactgagctgtgccgccagcggcttcacctttagcagctacgccatgaactgggtccgacaggccc ctggcaaaggactggaatgggtggccggaatcatcggcagcggcggcagcacatattacgccgattctgtgaagggccgcttcagcatc agccgggacaacagcaagaacaccctggacctgcagatgaacagcctgagagccgaggataccgccgtgtactactgcgtgaaggatt ggaacaccaccatgatcaccgagagaggccagggcacactggtcaccgtgtcctctacaacaacaccggcgcctcggcctccaacacc agctcctacaatcgcgagtcagcccctgtctctcagacccgaagcctgtagacctgctgctggcggagctgtgcataccagaggactggat ttcgcctgcgacatctacatctgggctcctctggctggcacatgcggagttttgctgctgagcctggtcatcaccctgtactgtaagagaggc aggaagaagctgctgtatatcttcaagcagcccttcatgagacccgtgcagaccacacaggaggaggacggctgctcttgtaggttcccag aggaggaggagggaggatgcgagctgcgcgtgaagtttagccggtccgccgatgcacctgcatacaagcagggacagaaccagctgta taacgagctgaatctgggccggagagaggagtacgacgtgctggataagaggcggggccgggaccccgagatgggaggcaagcctc ggagaaagaacccacaggagggcctgtacaatgagctgcaaaaggacaagatggccgaggcctattctgagatcggcatgaagggaga gaggcgccggggcaagggacacgatggcctgtaccagggcctgagcaccgccacaaaggacacctatgatgccctgcacatgcaggc cctgccccctagatga (VH-A; SEQ ID NO: 18001). [09] In certain embodiments of the VCARs of the disclosure, the VHH comprises or consists of the amino acid sequence malpvtalllplalllhaarpevqllesggglvqpggsltlscaasgftfsnyamnwvrqapgkglewvsgiigsgattyyadsvkgrfti srdnskntlnlqmnslraedtaiyycvkdwnttmitergqgtlvtvsstttpaprpptpaptiasqplslrpeacrpaaggavhtrgldfac diyiwaplagtcgvlllslvitlyckrgrkkllyifkqpfmrpvqttqeedgcscrfpeeeeggcelrvkfsrsadapaykqgqnqlynel nlgrreeydvldkrrgrdpemggkprrknpqeglynelqkdkmaeayseigmkgerrrgkghdglyqglstatkdtydalhmqalp pr (VH-B; SEQ ID NO: 18002) or the VHH comprises or consists of the nucleic acid sequence atggctctgcctgtgacagctctgctgctgcctctggctctgcttcttcatgcggcgcgccctgaagttcagctgcttgaatctggcggaggc ctggttcaacctggcggatctctgacactgagctgtgccgccagcggcttcaccttcagcaactacgccatgaactgggtccgacaggccc ctggcaaaggccttgaatgggtgtccggcatcattggctctggcgccaccacctactacgccgattctgtgaagggcagattcaccatcagc cgggacaacagcaagaacaccctgaacctgcagatgaacagcctgagagccgaggacaccgccatctactactgcgtgaaggactgga acaccaccatgatcaccgagagaggccagggcacactggtcaccgtgtcctctacaacaacaccggcgcctcggcctccaacaccagct cctacaatcgcgagtcagcccctgtctctcagacccgaagcctgtagacctgctgctggcggagctgtgcataccagaggactggatttcg cctgcgacatctacatctgggctcctctggctggcacatgcggagttttgctgctgagcctggtcatcaccctgtactgtaagagaggcagg aagaagctgctgtatatcttcaagcagcccttcatgagacccgtgcagaccacacaggaggaggacggctgctcttgtaggttcccagagg aggaggagggaggatgcgagctgcgcgtgaagtttagccggtccgccgatgcacctgcatacaagcagggacagaaccagctgtataa cgagctgaatctgggccggagagaggagtacgacgtgctggataagaggcggggccgggaccccgagatgggaggcaagcctcgga gaaagaacccacaggagggcctgtacaatgagctgcaaaaggacaagatggccgaggcctattctgagatcggcatgaagggagagag gcgccggggcaagggacacgatggcctgtaccagggcctgagcaccgccacaaaggacacctatgatgccctgcacatgcaggccct gccccctagatga (VH-B; SEQ ID NO: 18003). [010] In certain embodiments of the VCARs of the disclosure, the VHH comprises or consists of the amino acid sequence malpvtalllplalllhaarpevqllesggglvqpgeslrlscaasgftfsnyamnwvrqapgkglewvsgivggggtsyyadsvrgrft isrdnskntlylqmnslraedtavyycvkdwnttmitergqgtlvtvsstttpaprpptpaptiasqplslrpeacrpaaggavhtrgldfa cdiyiwaplagtcgvlllslvitlyckrgrkkllyifkqpfmrpvqttqeedgcscrfpeeeeggcelrvkfsrsadapaykqgqnqlyne
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