CHIMERIC ANTIGEN RECEPTORS (CARs), COMPOSITIONS AND METHODS THEREOF

Abstract

The present disclosure relates to compositions and methods relating to chimeric antigen receptor (CAR) polypeptides and methods relating thereto. In one embodiment, the present disclosure relates to engineered cells having chimeric antigen receptor polypeptides directed to at least two targets. In another embodiment, the present disclosure relates to engineered cells having chimeric antigen receptor polypeptides and an enhancer moiety.

1 - 104 . (canceled) 
     
     
         105 . An engineered T cell or NK cell comprising a nucleotide sequence comprising from 5′ to 3′ a first polynucleotide encoding a first chimeric antigen receptor polypeptide (CAR), a nucleotide encoding a first self-cleavage peptide, and a second polynucleotide encoding a second chimeric antigen receptor polypeptide (CAR), wherein:
 (i) the first CAR comprises a first signal peptide, a first antibody binding domain, a first hinge region, a first transmembrane domain, a first co-stimulatory domain, and a first signaling domain; and 
 (ii) the second CAR comprises a second signal peptide, a second antibody binding domain, a second hinge region, a second transmembrane domain, a second co-stimulatory domain, and a second signaling domain; wherein the first antibody binding domain and the second antibody binding domain are different from each other and each bind to a different target, wherein the targets of the first and second antibody binding domains irrespective of order are CD7 and CD19, CD7 and BCMA, and CD7 and CD5, wherein the first and second co-stimulatory domains are intracellular, and wherein the cleavage site is selected from the group consisting of porcine teschovirus-1 2A (P2A), thoseaasigna virus 2A (T2A), equine rhinitis A virus (ERAV) 2A (E2A), and FMDV 2A (F2A). 
 
     
     
         106 . The engineered T cell or NK cell according to  claim 105 , wherein the T-cell is a CD4 T-cell or CD8 T-cell. 
     
     
         107 . The engineered T cell or KK cell according to  claim 105 , wherein the NK cell is a NKT cell or NK-92cell. 
     
     
         108 . The engineered T cell or NK cell according to  claim 105 , further comprising a nucleotide encoding an enhancer, wherein the enhancer is selected from the group consisting of PD-1, PD-L1, CSF1R, CTAL-4, TIM-3, TGFR beta, IL-2, IL-6, IL-7, IL-12, IL-15, IL-17, IL-18 IL-21, functional fragments thereof, and combinations thereof, and wherein the enhancer is attached to either end of the 5′ to 3′ nucleotide sequence via a nucleotide encoding a second self-cleavage peptide. 
     
     
         109 . The engineered T cell or NK cell according to  claim 108 , wherein said enhancer is IL-15 or IL-15/IL-15sushi. 
     
     
         110 . A method of reducing the number of cells having at least one cell surface antigen selected from the group consisting of CD7, CD19, BCMA (CD269) and CD5 in a patient in need thereof, said method comprising administering to said patient an engineered T cell or NK cell according to  claim 105 .