Expansion of tils utilizing akt pathways inhibitors

A method for treating a subject with cancer, the method comprising administering expanded tumor infiltrating lymphocytes (TILs) comprising:

• (a) obtaining a first population of TILs from a tumor obtained from the subject;
• (b) performing a first expansion by culturing the first population of TILs in a cell culture medium comprising IL-2 and one or more AKT pathway inhibitor to produce a second population of TILs, wherein the first expansion is performed in a closed system comprising a closed container providing a first gas-permeable surface area, wherein the first expansion is performed for about 3-14 days to obtain the second population of TILs, wherein the second population of TILs is at least 50-fold greater in number than the first population of TILs, and wherein the transition from step (a) to step (b) occurs without opening the system;
• (c) performing a second expansion by supplementing the cell culture medium of the second population of TILs with additional IL-2, OKT-3, and antigen presenting cells (APCs) and culturing to produce a third population of TILs, wherein the second expansion is performed for about 7-14 days to obtain the third population of TILs, wherein the third population of TILs is a therapeutic population of TILs which comprises an increased subpopulation of effector T cells and/or central memory T cells relative to the second population of TILs, wherein the second expansion is performed in the closed system in a second closed container providing a second gas-permeable surface area, and wherein the transition from step (b) to step (c) occurs without opening the system;
• (d) harvesting the therapeutic population of TILs obtained from step (b), wherein the transition from step (c) to step (d) occurs without opening the system;
• (e) administering a therapeutically effective dosage of the harvested therapeutic population of TILs from step (d) to the subject.

A method for expanding tumor infiltrating lymphocytes (TTLs) into a therapeutic population of TTLs comprising:

• (a) obtaining a first population of TILs from a tumor resected from a subject by processing a tumor sample obtained from the subject into multiple tumor fragments;
• (b) performing a priming first expansion by culturing the first population of TTLs in a cell culture medium comprising IL-2, OKT-3, one or more AKT pathway inhibitor (AKTi), and antigen presenting cells (APCs) to produce a second population of TTLs, wherein the priming first expansion is performed in a container comprising a first gas-permeable surface area, wherein the priming first expansion is performed for first period of about 1 to 7 days to obtain the second population of TTLs, wherein the second population of TILs is greater in number than the first population of TTLs;
• (c) performing a rapid second expansion by supplementing the cell culture medium of the second population of TTLs with additional IL-2, OKT-3, and APCs, to produce a third population of TTLs, wherein the number of APCs added in the rapid second expansion is at least twice the number of APCs added in step (b), wherein the rapid second expansion is performed for a second period of about 1 to 11 days to obtain the third population of TTLs, wherein the third population of TTLs is a therapeutic population of TTLs, wherein the rapid second expansion is performed in a container comprising a second gas-permeable surface area;
• (d) harvesting the therapeutic population of TILs obtained from step (c);
• and
• (e) transferring the harvested TIL population from step (d) to an infusion bag.