CPC C07K 16/30 (2013.01) [A61K 31/436 (2013.01); A61K 38/1774 (2013.01); A61K 38/1793 (2013.01); A61K 39/001168 (2018.08); A61K 39/39558 (2013.01); A61K 48/0058 (2013.01); C07K 14/7051 (2013.01); C07K 14/70517 (2013.01); C07K 14/7151 (2013.01); C07K 16/303 (2013.01); C07K 16/3061 (2013.01); C07K 16/3069 (2013.01); C12N 5/0638 (2013.01); C12N 15/85 (2013.01); C12N 15/86 (2013.01); A61K 38/00 (2013.01); A61K 2039/505 (2013.01); A61K 2039/5158 (2013.01); C07K 2317/565 (2013.01); C07K 2317/622 (2013.01); C07K 2317/73 (2013.01); C07K 2317/92 (2013.01); C07K 2319/00 (2013.01); C07K 2319/02 (2013.01); C07K 2319/03 (2013.01); C07K 2319/74 (2013.01); C12N 2740/15041 (2013.01)] | 21 Claims |
1. An immune effector cell comprising a nucleic acid molecule comprising a nucleic acid sequence encoding a chimeric antigen receptor (CAR) wherein the CAR comprises:
i) a human anti-mesothelin binding domain comprising:
(a) a light chain variable region comprising: a light chain complementary determining region 1 (LC CDR1) comprising the amino acid sequence of SEQ ID NO: 209; a light chain complementary determining region 2 (LC CDR2) comprising the amino acid sequence of SEQ ID NO: 233; and a light chain complementary-determining region 3 (LC CL)R3) comprising the amino acid sequence of SEQ ID NO: 257; and
(b) a heavy chain variable region comprising: a heavy chain complementary determining region 1 (HC CDR1) comprising the amino acid sequence of SEQ ID NO: 144; a heavy chain complementary determining region 2 (HC CDR2) comprising the amino acid sequence of SEQ ID NO: 162; and a heavy chain complementary determining region 3 (HC CDR3) comprising the amino acid sequence of SEQ. ID NO: 185;
ii) a transmembrane domain selected from the transmembrane domain of a protein selected from the group consisting of the alpha, beta or zeta chain of the T-cell receptor, CD28, CD3 epsilon, CD45, CD4, CD5, CD8, CD9, CD16, CD22, CD33, CD37, CD64, CD80, CD86, CD134, CD137 and CD154;
iii) a costimulatory domain; and
iv) an intracellular signaling domain comprising the amino acid sequence of SEQ ID NO: 10;
wherein the isolated nucleic acid molecule does not comprise a nucleic acid sequence encoding an inducible promoter;
wherein the CAR is not a regulatable CAR; and
wherein the immune effector cell expresses a protein comprising a first polypeptide comprising an extracellular portion of PD1, PD-L1, CEACAM, LAG3, CTLA4, VISTA, CD160, BMA, LAIR1, TIM3, 2B4 or TIGIT and a second polypeptide comprising a costimulatory domain and/or a primary signaling domain.
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