Anti-tumor t cell immunity induced by high dose radiation

Abstract

Cancer treatment is provided, by irradiating an individual with a localized, high single dose or short course of doses at a primary tumor site; collecting T cells from the individual after a period of time sufficient activation of an anti-tumor response; treating the individual with an effective dose of dose of chemotherapy; and reintroducing the T cell population back to the individual.

What is claimed is: 
     
         1 . A method for treating a cancer in a subject, the method comprising:
 a. activating T cells with a high dose of localized radiation at a tumor site;   b. collecting a population of cells comprising the activated T cells and hematopoietic stem cells; and   c. administering the collected population of cells to the subject, thereby treating the cancer.   
     
     
         2 . The method of  claim 1 , wherein the high dose of localized radiation comprises a total dose of 20 to 40 Gy. 
     
     
         3 . The method of  claim 2 , wherein the high dose of localized radiation is delivered in a single dose. 
     
     
         4 . The method of  claim 2 , wherein the high dose of localized radiation is delivered in fractionated doses over a period of time of not more than one week. 
     
     
         5 . The method of  claim 1 , wherein (a) is performed over a time period from 2 to 6 weeks. 
     
     
         6 . The method of  claim 1 , further comprising purifying the activated T cells from regulatory T cells and purge tumor cells in the collected population of cells. 
     
     
         7 . The method of  claim 1 , wherein the collected population of cells comprises allogeneic cells. 
     
     
         8 . The method of  claim 1 , wherein the collected population of cells comprises autologous cells. 
     
     
         9 . The method of  claim 1 , wherein the collected population of cells comprises CD34 +  cells. 
     
     
         10 . The method of  claim 1 , wherein activated T cells comprises CD8 +  T cells, wherein the CD8 +  T cells are activated by the high dose of localized radiation at the tumor site to recognize the cancer. 
     
     
         11 . The method of  claim 1 , wherein the collected population of cells comprises at least 1×10 6  CD8 +  T cells. 
     
     
         12 . The method of  claim 11 , further comprising enriching the CD8 +  T cells from the collected population of cells. 
     
     
         13 . The method of  claim 11 , further comprising purifying the CD8 +  T cells from the collected population of cells. 
     
     
         14 . The method of  claim 1 , wherein administering the collected population of cells provides for durable remission of the cancer. 
     
     
         15 . The method of  claim 1 , wherein administering the collected population of cells prevents growth of metastases at a site other than the tumor. 
     
     
         16 . The method of  claim 1 , wherein administering the collected population of cells stimulates an immune system of the subject to target cancer cells. 
     
     
         17 . The method of  claim 1 , wherein the cancer is in an advanced state. 
     
     
         18 . The method of  claim 1 , wherein the cancer is metastatic. 
     
     
         19 . The method of  claim 1 , wherein the subject has been treated with an effective dose of chemotherapy prior to administering the collected population of cells. 
     
     
         20 . The method of  claim 19  wherein the effective dose of chemotherapy is a non-myeloablative dose. 
     
     
         21 . The method of  claim 19 , wherein the effective dose of chemotherapy is a myeloablative dose. 
     
     
         22 . The method of  claim 1 , wherein the cancer is a liver cancer, a lung cancer, a brain cancer, a pancreas cancer, a melanoma cancer, or a breast cancer. 
     
     
         23 . The method of  claim 1 , wherein the subject is a mammal.