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US 12,637,511 B2Granted
Methods for expansion of tumor infiltrating lymphocytes and use thereof
AssigneeBoard of Regents, The University of Texas System
InventorsMarie-Andrée Forget, Chantale Bernatchez, Cara Haymaker, Michael A Curran, Patrick Hwu, Cassian Yee
Life of this patent
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Abstract
Provided herein are methods for the activation and expansion of genetically-modified Tcells, such as tumor infiltrating lymphocytes. In some cases, cells of the embodiments can be used for the therapeutic treatment of human diseases, such as cancer.
Claims18
An ex vivo method for activation and expansion of T cells comprising:
- (a) pre-activating a starting population of T cells in the presence of an agonistic 4-1BB antibody and an anti-CD3 antibody to generate pre-activated T cells;
- (b) further activating the pre-activated T cells in the presence of IL-2 and anti-CD3 antibody, wherein the activation is performed in the absence of the agonistic 4-1BB of step (a) antibody, to generate activated T cells;
- (c) genetically modifying the activated T cells to obtain genetically modified T cells;
- and
- (d) expanding the genetically modified T cells in the presence of IL-2 and feeder cells to produce a population of expanded T cells, wherein steps (a)-(d) are performed in less than 6 weeks, wherein the agonistic 4-1BB antibody is an isolated monoclonal antibody, wherein the antibody specifically binds to 4-1BB and comprises:
- (a) a first VH CDR is identical to SEQ ID NO:
- 3;
- (b) a second VH CDR is identical to SEQ ID NO:
- 5;
- (c) a third VH CDR is identical to SEQ ID NO:
- 7;
- (d) a first VL CDR is identical to SEQ ID NO:
- 11;
- (e) a second VL CDR is identical to SEQ ID NO:
- 13;
- and
- (f) a third VL CDR is identical to SEQ ID NO:
- 15;
- or
- (a) a first VH CDR is identical to SEQ ID NO:
- 19;
- (b) a second VH CDR is identical to SEQ ID NO:
- 21;
- (c) a third VH CDR is identical to SEQ ID NO:
- 23;
- (d) a first VL CDR is identical to SEQ ID NO:
- 27;
- (e) a second VL CDR is identical to SEQ ID NO:
- 29;
- and
- (f) a third VL CDR is identical to SEQ ID NO:
- 31;
- or
- (a) a first VH CDR is identical to SEQ ID NO:
- 35;
- (b) a second VH CDR is identical to SEQ ID NO:
- 37;
- (c) a third VH CDR is identical to SEQ ID NO:
- 39;
- (d) a first VL CDR is identical to SEQ ID NO:
- 43;
- (e) a second VL CDR is identical to SEQ ID NO:
- 45;
- and
- (f) a third VL CDR is identical to SEQ ID NO:
- 47;
- or
- (a) a first VH CDR is identical to SEQ ID NO:
- 51;
- (b) a second VH CDR is identical to SEQ ID NO:
- 53;
- (c) a third VH CDR is identical to SEQ ID NO:
- 55;
- (d) a first VL CDR is identical to SEQ ID NO:
- 59;
- (e) a second VL CDR is identical to SEQ ID NO:
- 61;
- and
- (f) a third VL CDR is identical to SEQ ID NO:
- 63.
57 more elements
Dependencies are inferred from the claim text.