Processes for production of tumor infiltrating lymphocytes and uses of the same in immunotherapy

Patent metadata

Field	Value
Publication number	US-12280140-B2
Application number	US-202418411991-A
Country	US
Kind code	B2
Filing date	Jan 12, 2024
Priority date	Nov 5, 2018
Publication date	Apr 22, 2025
Grant date	Apr 22, 2025

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.

First claim

What is claimed is:

1. A method for expanding tumor infiltrating lymphocytes (TILs) into a therapeutic population of TILs, the method comprising:
(a) adding into a first closed container in a closed system system a plurality of tumor fragments comprising a first population of TILs obtained by processing a sample of tumor tissue resected from a subject with endometrial cancer into the plurality of tumor fragments;
(b) performing a first expansion by culturing the 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 in the first closed container providing a first gas-permeable surface area, wherein the first expansion is performed for about 3 to 11 days to obtain the second population of TILs;
(c) performing a second expansion by supplementing the cell culture medium with additional IL-2, OKT-3, and antigen presenting cells (APCs), to produce a third population of TILs, wherein the second expansion is performed in a second closed container providing a second gas-permeable surface area, wherein the second expansion is performed for about 7 to 11 days in order to obtain the third population of TILs, wherein the third population of TILs is a therapeutic population of TILs, 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 (c), wherein the transition from step (c) to step (d) occurs without opening the system;
(e) transferring the harvested therapeutic population of TILs from step (d) into an infusion bag, wherein the transition from step (d) to step (e) occurs without opening the system; and
(f) cryopreserving the infusion bag comprising the harvested TIL population from step (e) using a cryopreservation process.

2. The method of claim 1 , wherein the second population of TILs is at least 50-fold greater in number than the first population of TILs.

3. The method according to claim 1 , wherein the therapeutic population of TILs harvested in step (d) comprises sufficient TILs for use in administering a therapeutically effective dosage to the subject.

4. The method according to claim 3 , wherein the therapeutically effective dosage comprises from about 1×10 9 to about 1×10 11 TILs.

5. The method according to claim 1 , wherein the APCs are peripheral blood mononuclear cells (PBMCs).

6. The method according to claim 5 , wherein the PBMCs are allogenic irradiated PBMCs.

7. The method according to claim 5 , wherein a ratio of TILs:PBMCs is about 1:25.

8. The method according to claim 1 , wherein the therapeutic population of TILs harvested in step (d) exhibits an increased subpopulation of CD8+ cells relative to the first and/or second population of TILs.

9. The method according to claim 1 , wherein steps (a) through (e) are performed in about 10 days to about 22 days.

10. The method according to claim 1 , wherein steps (a) through (e) are performed in about 15 days to about 22 days.

11. The method according to claim 1 , wherein steps (a) through (e) are performed in about 20 days to about 22 days.

12. The method according to claim 1 , wherein the first closed container in step (a) and step (b) is a gas-permeable bag, and/or wherein the second closed container in step (c) is a gas-permeable bag.

Assignees

• Iovance Biotherapeutics Inc

Inventors

• Wardell Seth
• Moreno Maritza Lienlaf

Classifications

• A61K40/42

  Cancer antigens · CPC title

• A61K40/11

  T-cells, e.g. tumour infiltrating lymphocytes [TIL] or regulatory T [Treg] cells; Lymphokine-activated killer [LAK] cells · CPC title

• C12N2502/11

  blood or immune system cells · CPC title

• C12N2501/2302

  Interleukin-2 (IL-2) · CPC title

• C07K16/2809

  against the T-cell receptor (TcR)-CD3 complex · CPC title