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US 11,401,507 B2Granted
Remnant tumor infiltrating lymphocytes and methods of preparing and using the same
AssigneeIovance Biotherapeutics, Inc.
InventorsMichelle R. Simpson-Abelson, Christopher Mosychuk, Michael T. Lotze
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Abstract
In some embodiments, methods of delivering a therapeutically effective amount of an expanded number of tumor infiltrating lymphocytes obtained from tumor remnants to a patient in need thereof, for the treatment of a cancer, are disclosed.
Claims28
A method for preparing remnant tumor infiltrating lymphocytes (rTILs) for adoptive T cell therapy, the method comprising:
- (a) obtaining tumor tissue from a patient, wherein the tumor tissue comprises tumor infiltrating lymphocytes (TILs);
- (b) fragmenting the tumor tissue to provide a fragmented tumor tissue;
- (c) treating the fragmented tumor tissue in a gas permeable container with a first cell culture medium and interleukin 2 (IL-2) to provide emergent TILs (eTILs) and tumor remnants comprising remnant TILs (rTILs);
- (d) removing at least a plurality of the eTILs;
- (e) enzymatically digesting the tumor remnants into tumor remnant cells using a digest mixture;
- and
- (f) expanding the tumor remnant cells with a second cell culture medium comprising cell culture media, irradiated feeder cells, OKT-3 antibody, and IL-2 in a gas permeable container to provide an expanded number of the rTILs;
- wherein the rTILs express reduced levels of a T cell exhaustion marker relative to the eTILs, and wherein the T cell exhaustion marker is selected from the group consisting of TIM3, LAG3, TIGIT, PD-1, CTLA-4, and combinations thereof.
5 more elements
Dependencies are inferred from the claim text.