Methods of growing tumor infiltrating lymphocytes in gas-permeable containers

Abstract

An embodiment of the invention provides a method of promoting regression of cancer in a mammal comprising obtaining a tumor tissue sample from the mammal; culturing the tumor tissue sample in a first gas permeable container containing cell medium therein; obtaining tumor infiltrating lymphocytes (TIL) from the tumor tissue sample; expanding the number of TIL in a second gas permeable container containing cell medium therein using irradiated allogeneic feeder cells and/or irradiated autologous feeder cells; and administering the expanded number of TIL to the mammal. Methods of obtaining an expanded number of TIL from a mammal for adoptive cell immunotherapy are also provided.

1 . (canceled) 
     
     
         2 . A method of obtaining an expanded number of tumor infiltrating lymphocytes (TIL) from a mammal for adoptive cell immunotherapy comprising:
 (a) obtaining a tumor tissue sample from the mammal;   (b) culturing the tumor tissue sample in a first gas permeable container comprising a cell medium and IL-2;   (c) obtaining TIL from the tumor tissue sample; and   (d) expanding the number of TIL in a second gas permeable container comprising a cell medium, irradiated feeder cells, IL-2, and OKT3.   
     
     
         3 . The method of  claim 2 , wherein the first permeable container further comprises IL-15. 
     
     
         4 . The method of  claim 2 , wherein the second permeable container further comprises IL-15. 
     
     
         5 . The method of  claim 2 , wherein the irradiated feeder cells comprise allogenic feeder cells. 
     
     
         6 . The method of  claim 2 , wherein the irradiated feeder cells comprise autologous feeder cells. 
     
     
         7 . The method of  claim 2 , wherein the irradiated feeder cells comprise irradiated peripheral blood mononuclear cells (PBMCs). 
     
     
         8 . The method of  claim 2 , wherein the step of expanding the number of TIL comprises expanding the number of TIL over a period of about 10 days to about 14 days. 
     
     
         9 . The method of  claim 8 , wherein the period is about 14 days. 
     
     
         10 . The method of  claim 2 , wherein the method has a duration of about 28 days to about 42 days. 
     
     
         11 . The method of  claim 10 , wherein the duration is about 28 days. 
     
     
         12 . A method for promoting regression of cancer in a mammal comprising administering the expanded number of TIL of  claim 2  to the mammal. 
     
     
         13 . The method of  claim 12 , wherein the cancer is selected from the group consisting of acute lymphatic cancer, acute myeloid leukemia, alveolar rhabdomycosarcoma, bone cancer, brain cancer, breast cancer, cancer of the anus, anal canal or anorectum cancer, cancer of the eye, cancer of the intrahepatic bile duct cancer, cancer of the joints, cancer of the neck, gallbladder or pleura cancer, cancer of the nose, nasal cavity or middle ear, cancer of the oral cavity, cancer of the vulva, chronic lymphatic leukemia, chronic myeloid cancer, colon cancer, esophageal cancer, cervical cancer, gastrointestinal carcinoid tumor, glioma, Hodgkin lymphoma, hypopharynx cancer, kidney cancer, larynx cancer, liver cancer, lung cancer, malignant mesothelioma, melanoma, multiple myeloma, nasopharynx cancer, non-Hodgkin lymphoma, ovarian cancer, pancreatic cancer, peritoneum cancer, omentum and mesentary cancer, pharynx cancer, prostate cancer, rectal cancer, renal cancer, skin cancer, small intestine cancer, soft tissue cancer, stomach cancer, testicular cancer, thyroid cancer, ureter cancer, and urinary bladder cancer. 
     
     
         14 . The method of  claim 13 , wherein the cancer is melanoma. 
     
     
         15 . The method of  claim 12 , wherein the expanded number of TIL are administered as an intra-arterial infusion or an intravenous infusion. 
     
     
         16 . The method of  claim 12 , wherein the expanded number of TIL are administered through a route of administration selected from the group consisting of intraperitoneal administration, intrathecal administration, and intralymphatic administration. 
     
     
         17 . The method of  claim 12 , comprising administering a T-cell growth factor to the mammal, wherein the T-cell growth factor comprises one or more of IL-2 and IL-15. 
     
     
         18 . The method of  claim 17 , wherein the T-cell growth factor is IL-2. 
     
     
         19 . The method of  claim 17 , wherein the T-cell growth factor is administered to the mammal concomitantly with the expanded number of TIL. 
     
     
         20 . The method of  claim 17 , wherein the T-cell growth factor is administered to the mammal subsequently to the expanded number of TIL. 
     
     
         21 . The method of  claim 17 , wherein the T-cell growth factor is administered intravenously to the mammal.