Enhanced Expansion of Tumor-Infiltrating Lymphocytes for Adoptive Cell Therapy

• US 20170044496A1
• Filed: 04/10/2015
• Published: 02/16/2017
• Est. Priority Date: 04/10/2014
• Status: Abandoned Application

• Current Assignee: H Lee Moffitt Cancer Center & Research Institute (State University System of Florida), Board of Regents of the University of Texas System (University of Texas System)
• Original Assignee: H Lee Moffitt Cancer Center & Research Institute (State University System of Florida), Board of Regents of the University of Texas System (University of Texas System)
• Inventors: Sarnaik, Amod A., Weber, Jeffrey S., Pilon-Thomas, Shari, Radvanyi, Laszlo G., Chacon, Jessica Ann, Mule', James J.
• Application Number:
  US15/303,201
• Publication Number:
  US 20170044496A1
• Time in Patent Office: Days
• CPC Class Codes: A61K 2039/5158 Antigen-pulsed cells, e.g. T-cells
• CPC Class Codes: A61K 2239/49 Breast
• CPC Class Codes: A61K 2239/57 Skin; melanoma
• CPC Class Codes: A61K 35/17 Lymphocytes; B-cells; T-cells; Natural killer cells; Interferon-activated or cytokine-activated lymphocytes when activated by a specific antigen A61K39/00
• CPC Class Codes: A61K 39/0011 Cancer antigens
• CPC Class Codes: A61K 39/4611 T-cells, e.g. tumor infiltrating lymphocytes [TIL], lymphokine-activated killer cells [LAK] or regulatory T cells [Treg]
• CPC Class Codes: A61K 39/4636 Immune checkpoint inhibitors
• CPC Class Codes: A61K 39/4644 Cancer antigens
• CPC Class Codes: A61K 39/464417 Receptors for tumor necrosis factors [TNF], e.g. lymphotoxin receptor [LTR], CD30
• CPC Class Codes: A61K 39/464491 Melan-A/MART
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C12N 2501/2302 Interleukin-2 (IL-2)
• CPC Class Codes: C12N 2501/25 Tumour necrosing factors [TNF]
• CPC Class Codes: C12N 2501/599 with CD designations not provided for elsewhere
• CPC Class Codes: C12N 2501/998 Proteins not provided for elsewhere
• CPC Class Codes: C12N 5/0638 Cytotoxic T lymphocytes [CTL] or lymphokine activated killer cells [LAK]

Abstract

Disclosed herein is a method for ex vivo expanding tumor-infiltrating lymphocytes for use in adoptive cell therapy (ACT). The method involves culturing tumor fragments from the subject in a culture medium containing IL-2 and a 41BB agonist in an amount effective to expand tumor-infiltrating lymphocytes with enriched tumor-reactivity and specificity. Also disclosed is a method for treating a tumor in a subject that involves treating the subject with nonmyeloablative lymphodepleting chemotherapy, and administering tumor-infiltrating lymphocytes expanded by the disclosed methods.

Claims

5-1. The method of claim 1, wherein the cancer is a solid tumor.

6-1. The method of claim 1, wherein the cancer is selected from the group consisting of melanoma, ovarian cancer, breast cancer, and colorectal cancer.