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US 2026/0144870 A1Published application
Processes for production of tumor infiltrating lymphocytes and uses of same in immunotherapy
AssigneeIovance Biotherapeutics, Inc.
InventorSeth WARDELL
Life of this patent
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Abstract
The present invention provides improved and/or shortened methods for expanding TILs and producing therapeutic populations of TILs, including novel methods for expanding TIL populations in a closed system that lead to improved efficacy, improved phenotype, and increased metabolic health of the TILs in a shorter time period, while allowing for reduced microbial contamination as well as decreased costs. Such TILs find use in therapeutic treatment regimens.
Claims24
A method for expanding tumor infiltrating lymphocytes (TILs) into a therapeutic population of TILs comprising:
- (a) optionally pre-treating a patient with a regimen comprising a kinase inhibitor or an ITK inhibitor;
- (b) obtaining a first population of TILs from a tumor resected from a patient by processing a tumor sample obtained from the patient into multiple tumor fragments or adding processed tumor fragments from a tumor resected from the patient into a closed system to obtain a first population of TILs;
- (c) adding the tumor fragments into a closed system;
- (d) performing a first expansion by culturing the first population of TILs in a cell culture medium comprising IL-2, and optionally OKT-3, to produce a second population of TILs, wherein the first expansion is performed in a closed container providing a first gas-permeable surface area, wherein the first expansion is performed for a first period of about 3-14 days to obtain the second population of TILs, and wherein the transition from step (c) to step (d) occurs without opening the system;
- (e) performing a second expansion by supplementing the cell culture medium of the second population of TILs with additional IL-2, optionally OKT-3, and antigen presenting cells (APCs), to produce a third population of TILs, wherein the second expansion is performed for a second period of about 7-14 days to obtain the third population of TILs, wherein the third population of TILs is a therapeutic population of TILs, wherein the second expansion is performed in a closed container providing a second gas-permeable surface area, and wherein the transition from step (d) to step (e) occurs without opening the system;
- (f) harvesting the therapeutic population of TILs obtained from step (e), wherein the transition from step (e) to step (f) occurs without opening the system;
- and
- (g) transferring the harvested TIL population from step (f) to an infusion bag, wherein the transfer from step (f) to (g) occurs without opening the system.
5 more elements
2-44. (canceled)
A method for treating a subject with cancer, the method comprising administering expanded tumor infiltrating lymphocytes (TILs) comprising:
- (a) pre-treating the subject with a regimen comprising a kinase inhibitor or an IL-2-inducible T-cell kinase (ITK) inhibitor;
- (b) obtaining a first population of TILs from a tumor resected from the subject by processing a tumor sample obtained from the subject into multiple tumor fragments;
- (c) adding the tumor fragments into a closed system;
- (d) performing a first expansion by culturing the first population of TILs in a cell culture medium comprising IL-2, and optionally OKT-3, to produce a second population of TILs, wherein the first expansion is performed in a closed container providing a first gas-permeable surface area, wherein the first expansion is performed for a first period of about 3-14 days to obtain the second population of TILs, and wherein the transition from step (c) to step (c) occurs without opening the system;
- (e) performing a second expansion by supplementing the cell culture medium of the second population of TILs with additional IL-2, optionally OKT-3, and antigen presenting cells (APCs), to produce a third population of TILs, wherein the second expansion is performed for a second period of about 7-14 days to obtain the third population of TILs, wherein the third population of TILs is a therapeutic population of TILs, wherein the second expansion is performed in a closed container providing a second gas-permeable surface area, and wherein the transition from step (d) to step (e) occurs without opening the system;
- (f) harvesting the therapeutic population of TILs obtained from step (e), wherein the transition from step (e) to step (f) occurs without opening the system;
- and
- (g) transferring the harvested TIL population from step (f) to an infusion bag, wherein the transfer from step (f) to (g) occurs without opening the system;
- (h) optionally cryopreserving the infusion bag comprising the harvested TIL population from step (g) using a cryopreservation process;
- and
- (i) administering a therapeutically effective dosage of the third population of TILs from the infusion bag in step (h) to the subject.
8 more elements
(canceled)
62-98. (canceled)
100-145. (canceled)
A method for treating a subject with cancer, the method comprising administering expanded tumor infiltrating lymphocytes (TILs) comprising:
- (a) pre-treating the subject with a regimen comprising a kinase inhibitor or an IL-2-inducible T-cell kinase (ITK) inhibitor;
- (b) obtaining a first population of TILs from a tumor resected from the subject by processing a tumor sample obtained from the subject into multiple tumor fragments;
- (c) adding the tumor fragments into a closed system;
- (d) performing a first expansion by culturing the first population of TILs in a cell culture medium comprising IL-2, optionally OKT-3, and optionally a tumor necrosis factor receptor superfamily (TNFRSF) agonist, to produce a second population of TILs, wherein the first expansion is performed in a closed container providing a first gas-permeable surface area, wherein the first expansion is performed for a first period of about 3-14 days to obtain the second population of TILs, and wherein the transition from step (c) to step (d) occurs without opening the system;
- (e) performing a second expansion by supplementing the cell culture medium of the second population of TILs with additional IL-2, optionally OKT-3, and optionally a tumor necrosis factor receptor superfamily (TNFRSF) agonist, and antigen presenting cells (APCs), to produce a third population of TILs, wherein the second expansion is performed for a second period of about 7-14 days to obtain the third population of TILs, wherein the third population of TILs is a therapeutic population of TILs, wherein the second expansion is performed in a closed container providing a second gas-permeable surface area, and wherein the transition from step (d) to step (e) occurs without opening the system;
- (f) harvesting the therapeutic population of TILs obtained from step (e), wherein the transition from step (f) to step (g) occurs without opening the system;
- and
- (g) transferring the harvested TIL population from step (f) to an infusion bag, wherein the transfer from step (f) to (g) occurs without opening the system;
- (h) optionally cryopreserving the infusion bag comprising the harvested TIL population from step (g) using a cryopreservation process;
- and
- (i) administering a therapeutically effective dosage of the third population of TILs from the infusion bag in step (h) to the subject.
8 more elements
Dependencies are inferred from the claim text.