Til expansion processes using specific cytokine combinations and/or akti treatment
AssigneeIovance Biotherapeutics, Inc.
InventorsTim ERICKSON, Andrew YUHAS, Rafael CUBAS
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Abstract
Provided herein are methods of producing TILs via (i) pre-REP stimulation with a combination of interferon gamma (IFNγ) and an anti-PD-1 antibody, with or without a CD40 agonist, and with or without an anti-CTLA-4 antibody (ii) various concentrations of IL-15 and IL-21, with or without low-concentration IL-2, with or without an AKT inhibitor (AKTi) during REP expansion and/or pre-REP expansion, (iii) low-concentration IL-2 and an AKTi during REP expansion and/or pre-REP expansion, (iv) the combination of (i) and (ii), or (v) the combination of (i) and (iii).
Claims30
A method of making a population of tumor infiltrating lymphocytes (TILs), the method comprising the steps of:
- (a) performing a first expansion by culturing a tumor sample obtained from a cancer patient to generate a first population of TILs in a cell culture medium comprising IL-2 to produce a second population of TILs, wherein the first expansion is performed for about 3-14 days to obtain the second population of TILs;
- (b) performing a second expansion by culturing the second population of TILs in a cell culture medium having IL-2 at a concentration of 3000 IU/mL or lower, OKT-3, and antigen presenting cells (APCs), 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 comprises a therapeutic population of TILs;
- (c) harvesting the third population of TILs obtained from step (b);
- and
- (d) transferring the harvested third population of TILs from step (c) to an infusion bag.
Dependencies are inferred from the claim text.