Polyclonal gamma delta t cells for immunotherapy

Abstract

Provided herein is a method of expanding clinically-relevant quantities of polyclonal γδ T cells that have anti-tumor, anti-viral, and anti-bacterial reactivity. Polyclonal γδ T cells can target a variety of tumors, including solid tumors as well as other conditions, such as viral and bacterial infections.

1 .- 20 . (canceled) 
     
     
         21 . A cell composition comprising at least about 10 9  purified γδ T cells, wherein the γδ T cells are of the Vδ1, Vδ2, and Vδ1 neg Vδ2 neg  TCR subsets, and are genetically modified to express a chimeric antigen receptor and a membrane bound IL-15. 
     
     
         22 . The cell composition of  claim 21 , wherein the composition does not contain NK cells or αβ T cells. 
     
     
         23 . The cell composition of  claim 21 , wherein the γδ T cells express CD3. 
     
     
         24 . The cell composition of  claim 21 , wherein the γδ T cells do not express CD57 or PD-1. 
     
     
         25 . A pharmaceutical composition comprising a cell composition according to  claim 21  and a pharmaceutically acceptable carrier. 
     
     
         26 . A method of treating a disease in a patient comprising administering an effective amount of a cell composition according to  claim 21 . 
     
     
         27 . The method of  claim 26 , wherein the disease is cancer. 
     
     
         28 . The method of  claim 27 , wherein the cancer is T-cell ALL, B-ALL, CML, colon cancer, ovarian cancer, neuroblastoma, a brain tumor, or pancreatic cancer. 
     
     
         29 . The method of  claim 26 , wherein the disease is a viral infection. 
     
     
         30 . The method of  claim 29 , wherein the viral infection is cytomegalovirus (CMV), Epstein-Barr virus (EBV), or human immunodeficiency virus (HIV). 
     
     
         31 . The method of  claim 26 , wherein the disease is a bacterial infection. 
     
     
         32 . The method of  claim 31 , wherein the disease is sepsis. 
     
     
         33 . The method of  claim 26 , wherein the cell composition is allogeneic to the patient. 
     
     
         34 . The method of  claim 26 , wherein the cell composition is autologous to the patient. 
     
     
         35 . A method of treating a disease in a patient comprising
 (a) obtaining a sample of cells comprising a first polyclonal γδ T-cell population;   (b) isolating the first polyclonal γδ T-cell population;   (c) culturing the first polyclonal γδ T-cell population with artificial antigen presenting cells (aAPCs) in the presence of interleukin-2 (IL-2) and interleukin-21 (IL-21), thereby inducing proliferation of the γδ T cells to sufficient numbers for use in therapy, wherein the aAPCs are engineered K562 cells that express CD137L, CD64, CD86, and mIL15   (d) isolating the cultured γδ T-cells and   (e) administering the cultured γδ T-cells to a patient.   
     
     
         36 . The method of  claim 35 , further comprising genetically modifying the cultured γδ T-cells to express a chimeric antigen receptor. 
     
     
         37 . The method of  claim 35 , further comprising genetically modifying the cultured γδ T-cells to express a membrane bound IL-15. 
     
     
         38 . The method of  claim 35 , wherein the disease is cancer. 
     
     
         39 . The method of  claim 38 , wherein the cancer is ALL, B-ALL, CML, colon cancer, ovarian cancer, or pancreatic cancer. 
     
     
         40 . The method of  claim 35 , wherein the disease is a viral infection. 
     
     
         41 . The method of  claim 40 , wherein the viral infection is cytomegalovirus (CMV), Epstein-Barr virus (EBV), or human immunodeficiency virus (HIV).