Tumor-infiltrating lymphocytes for adoptive cell therapy
AssigneesH. Lee Moffitt Cancer Center and Research Institute, Inc., University of South Florida
InventorsAmod A. Sarnaik, Shari Pilon-Thomas, Mark McLaughlin, Hao Liu
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Abstract
Disclosed are compositions and methods for ex vivo expansion of tumor infiltrating lymphocytes for use in adoptive cell therapy (ACT). Also disclosed are compositions and method for identifying an agent for ex vivo expansion of tumor infiltrating lymphocytes for use in ACT. Also disclosed are methods for treating cancer using tumor-infiltrating lymphocytes expanded by the disclosed methods.
Claims25
A method of producing ex vivo expanded tumor-infiltrating lymphocytes (TILs), the method comprising:
- (a) culturing TILs from a subject in a two-step process comprising:
- (i) a pre-rapid expansion (pre-REP) stage in a first culture medium in the presence of IL-2;
- and
- (ii) culturing the TILs from step (i) in a rapid expansion (REP) stage in a second culture medium, comprising reagents different from reagents of the first culture medium, in the presence of IL-2 to produce expanded TILs;
- and
- (b) adding a toll like receptor (TLR) agonist to one or more of the first culture medium and the second culture medium in an amount effective to improve the tumor-specificity of the expanded TILs, wherein the TLR agonist is a ligand for a TLR selected from the group consisting of TLR3, and TLR9.
A method for producing ex vivo expanded tumor-infiltrating lymphocytes (TILs) for use in adoptive cell therapy (ACT), comprising:
- (a) culturing autologous TILs from a subject in a two-step process comprising:
- (i) a pre-rapid expansion (pre-REP) stage in a first culture medium that comprises reagents comprising IL-2;
- and
- (ii) culturing the TILs from step (i) in a rapid expansion (REP) stage in a second culture medium that comprises reagents comprising IL-2 to produce expanded TILs, wherein the reagents from the second culture medium are different from the reagents from the first culture medium;
- and
- (b) adding a toll like receptor (TLR) agonist to one or more of the first culture medium and the second culture medium in an amount effective to improve the tumor-specificity of the expanded TILs, wherein the TLR agonist is a ligand for a TLR selected from the group consisting of TLR1, TLR2, and TLR4.
A method for treating cancer in a subject comprising the steps of:
- (a) culturing autologous tumor-infiltrating lymphocytes (TILs) from a subject in a two-step process comprising:
- (i) a pre-rapid expansion (pre-REP) stage in a first culture medium that comprises reagents comprising IL-2;
- and
- (ii) culturing the TILs from step (i) in a rapid expansion (REP) stage in a second culture medium that comprises reagents comprising IL-2 to produce expanded TILs, wherein the reagents from the second culture medium are different from the reagents from the first culture medium;
- and
- (b) adding a toll like receptor (TLR) agonist to one or more of the first culture medium and the second culture medium in an amount effective to improve the tumor-specificity of the expanded TILs, wherein the TLR agonist is a ligand for a TLR selected from the group consisting of TLR3, and TLR9;
- (c) treating the subject with nonmyeloablative lymphodepleting chemotherapy, and
- (d) administering the expanded TILs to the subject.
A method for treating cancer in a subject comprising the steps of:
- (a) culturing autologous TILs from the subject in a two-step process comprising:
- (i) a pre-rapid expansion (pre-REP) stage in a first culture medium that comprises reagents comprising IL-2;
- and
- (ii) culturing the TILs from step (i) in a rapid expansion (REP) stage in a second culture medium that comprises reagents comprising IL-2 to produce expanded TILs, wherein the reagents from the second culture medium are different from the reagents from the first culture medium;
- and
- (b) adding a toll like receptor (TLR) agonist to one or more of the first culture medium and the second culture medium in an amount effective to improve the tumor-specificity of the expanded TILs, wherein the TLR agonist is a ligand for a TLR selected from the group consisting of TLR1, TLR2, and TLR4;
- (c) treating the subject with nonmyeloablative lymphodepleting chemotherapy, and
- (d) administering the expanded TILs to the subject.
Dependencies are inferred from the claim text.