Cell compositions and methods for cancer therapy

Abstract

The present invention is directed to the field of immunotherapy. Specifically, the invention provides compositions and methods for improved T cell modulation ex vivo and in vivo and for the treatment of cancer and other pathologies. More specifically, embodiments of the invention are directed to the use of soluble NTB-A polypeptides or agonists thereof for the treatment of cancer patients, for preventing and treating cytopenia in susceptible patients, and for the ex vivo preparation of improved cell compositions.

1 - 66 . (canceled) 
     
     
         67 . A method for treating cancer in a subject in need thereof, comprising:
 i) obtaining a CD8 +  T cell containing population from the subject, or from a donor substantially histocompatible with said subject,   ii) incubating the T cell containing cell population ex vivo with an effective amount of an isolated NTB-A ectodomain or an agonist thereof, wherein the agonist is an antibody specific to an NTB-A ectodomain, and   iii) administering the resulting T cell containing cell population to said subject,   
       thereby treating cancer in said subject. 
     
     
         68 . The method of  claim 67 , wherein the incubation is performed in the presence of T cell receptor (TCR) stimulation and feeder cells, and without the addition of exogenous IL-2. 
     
     
         69 . The method of  claim 67 , wherein the NTB-A ectodomain is human NTB-A ectodomain. 
     
     
         70 . The method of  claim 67 , wherein the CD8 +  T cell containing population comprises tumor infiltrating lymphocytes (TIL). 
     
     
         71 . The method of  claim 68 , wherein incubation is performed in the presence of an isolated NTB-A ectodomain, an anti-CD3 antibody and allogeneic feeder cells for 8 to 15 days, in an amount and under conditions effective to reduce activation-induced T cell death without the addition of exogenous IL-2. 
     
     
         72 . The method of  claim 67 , further comprising administering an effective amount of an isolated NTB-A ectodomain or an agonist thereof to said subject. 
     
     
         73 . The method of  claim 67 , wherein said subject is afflicted with a tumor characterized by lack of substantial NTB-A surface expression. 
     
     
         74 . The method of  claim 69 , wherein the isolated ectodomain lacks the signal peptide at positions 1-21 of NTB-A. 
     
     
         75 . The method of  claim 67 , wherein said subject is a cytopenic subject, or a subject at risk of developing cytopenia. 
     
     
         76 . The method of  claim 67 , wherein IL-2 is not exogenously administered to said subject. 
     
     
         77 . A method of reducing or inhibiting T cell death, comprising contacting T cells with an effective amount of an isolated NTB-A ectodomain or an agonist thereof, wherein the agonist is an antibody specific to human NTB-A ectodomain. 
     
     
         78 . The method of  claim 77  wherein the contacting is performed in vitro. 
     
     
         79 . The method of  claim 77  wherein the contacting is performed in vivo. 
     
     
         80 . The method of  claim 77  for reducing or inhibiting T cell death in a subject suffering from or at risk of developing cytopenia. 
     
     
         81 . The method of  claim 77 , wherein the NTB-A ectodomain is human NTB-A ectodomain that lacks the signal peptide at positions 1-21 of NTB-A. 
     
     
         82 . A method of treating or preventing cytopenia in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of an isolated NTB-A ectodomain or an agonist thereof, wherein the agonist is an antibody specific to human NTB-A ectodomain, thereby treating or preventing cytopenia in said subject. 
     
     
         83 . The method of  claim 82  wherein the cytopenia is associated with radiation or chemotherapy. 
     
     
         84 . The method of  claim 82  for the treatment or prevention of lymphocytopenia. 
     
     
         85 . The method of  claim 82  wherein said subject is not afflicted with X-linked lymphoproliferative disease (XLP), or wherein said subject is not afflicted with cancer. 
     
     
         86 . The method of  claim 82 , wherein the NTB-A ectodomain is human NTB-A ectodomain that lacks the signal peptide at positions 1-21 of NTB-A.