Administration of Engineered T Cells for Treatment of Cancers in the Central Nervous System

Abstract

An improved method of treating cancers with engineered T cells is described.

1 . A method of treating a patient diagnosed with a malignancy of the central nervous system comprising introducing into the cerebrospinal fluid (CSF) of the patient a composition comprising an effective amount of T cells. 
     
     
         2 . The method of  claim 1  wherein the T cells are autologous or allogenic T cells. 
     
     
         3 . The method of  claim 1  wherein the T cells have been manipulated ex vivo by one or more of: expansion, fractionation or transfection with a recombinant nucleic acid molecule. 
     
     
         4 . The method of  claim 3  wherein the T cells comprise cells that have been transfected with a recombinant nucleic acid molecule encoding a polypeptide that binds to a tumor cell antigen. 
     
     
         5 . The method of  claim 4  wherein the polypeptide is a chimeric antigen receptor. 
     
     
         6 . The method of  claim 1  wherein the composition is administered intraventricularly 
     
     
         7 . The method of  claim 1  wherein the composition is administered to the central canal of the spinal cord. 
     
     
         8 . The method of  claim 6  wherein the administration is to the left ventrical or the right ventrical. 
     
     
         9 . The method of  claim 1  wherein the composition comprises at least 1×10 6  cells. 
     
     
         10 . The method of  claim 1  wherein a composition comprising T cells is administered at least two times. 
     
     
         11 . The method of  claim 10  wherein the wherein the administrations differ in the total number of T cells administered. 
     
     
         12 . The method of  claim 10  wherein the administrations escalate in dose. 
     
     
         13 . The method of  claim 10  wherein the administration de-escalate in dose. 
     
     
         14 . The method of  claim 1  wherein the T cells comprise CAR T cells expressing a chimeric antigen receptor. 
     
     
         15 . The method of  claim 1  wherein the T cells comprise autologous tumor infiltrating lymphocytes. 
     
     
         16 . The method of  claim 1  wherein the T cells comprise TCR-engineered T cells. 
     
     
         17 . The method of  claim 1  wherein the malignancy is a diffuse, infiltrating tumor. 
     
     
         18 . The method of  claim 1  wherein the malignancy is a primary brain tumor. 
     
     
         19 . The method of  claim 1  wherein one or more tumor foci decrease in size by at least 25%. 
     
     
         20 . The method of  claim 1  wherein the malignancy arose from a primary cancer selected from: breast cancer, lung cancer, head and neck cancer, and melanoma. 
     
     
         21 . The method of  claim 1  wherein the method is performed after tumor resection. 
     
     
         22 . The method of  claim 1  further comprising intratumoral administration of a composition comprising T cells. 
     
     
         23 . The method of  claim 1  wherein the malignancy is secondary brain tumor. 
     
     
         24 . The method of  claim 1  further comprising intratumoral administration of a composition comprising therapeutic T cells expressing a chimeric antigen receptor that binds a protein expressed on the surface of glioblastoma cells. 
     
     
         25 . The method of  claim 24  wherein the patient has previously undergone resection of a tumor lesion. 
     
     
         26 .- 124 . (canceled)