Marrow infiltrating lymphocytes (mils) as a source of t-cells for chimeric antigen receptor (car) thereapy

Abstract

In some embodiments, marrow-infiltrating lymphocytes (“MILs”) comprising a chimeric antigen receptor (“CAR”) are provided. In some aspects, the embodiments relate to a MIL obtained from bone marrow comprising a chimeric antigen receptor. In some aspects, the embodiments relate to a method for treating a condition in a subject, comprising administering to the subject a MIL comprising a CAR.

1 - 35 . canceled 
     
     
         36 . A marrow infiltrating lymphocyte (“MIL”), comprising a chimeric antigen receptor (“CAR”), wherein the CAR comprises:
 a scFV antigen-binding domain that can bind to an extracellular domain of a ligand, 
 a transmembrane domain, and 
 an intracellular domain that can initiate an intracellular signaling cascade. 
 
     
     
         37 . The MIL of  claim 36 , wherein the MIL is selected from the group consisting of CD3+, CD4+, CD8+, CD45RO+, CD62L +, or CXCR4+, 4-1BB+, CD138+, CD33+, CD34-, interferon γ+, and combinations thereof. 
     
     
         38 . The MIL of  claim 36 , wherein the ligand is a molecule expressed on a neoplastic cell. 
     
     
         39 . The MIL of  claim 38 , wherein the ligand is tumor antigen. 
     
     
         40 . The MIL of  claim 39 , wherein the tumor antigen is CD20, CD22, ROR1, Mesothelin, CD33/IL3Ra, c-Met, Glycolipid F77, EGFRvIII, GD-2, NY-ESO-1, or MAGE-A3. 
     
     
         41 . The MIL of  claim 36 , wherein the transmembrane domain is a transmembrane region of the α, β, or ζ chain of the T-cell receptor, CD8, CD3ζ, CD45, CD4, CD5, CD8, CD9, CD16, CD22, CD33, CD37, CD64, CD80, CD86, CD137, or CD154. 
     
     
         42 . The MIL of  claim 36 , wherein the intracellular domain is the cytoplasmic region of the T-cell receptor, CD3ζ, CD28, or 4-1BB.