TUMOR-INFILTRATING LYMPHOCYTES FOR ADOPTIVE CELL THERAPY

• US 20170081635A1
• Filed: 03/20/2015
• Published: 03/23/2017
• Est. Priority Date: 03/20/2014
• Status: Abandoned Application

• Current Assignee: H Lee Moffitt Cancer Center & Research Institute (State University System of Florida), University of South Florida (State University System of Florida)
• Original Assignee: H Lee Moffitt Cancer Center & Research Institute (State University System of Florida), University of South Florida (State University System of Florida)
• Inventors: Sarnaik, Amod A., Pilon-Thomas, Shari, McLaughlin, Mark, Liu, Hao
• Application Number:
  US15/126,436
• Publication Number:
  US 20170081635A1
• Time in Patent Office: Days
• CPC Class Codes: A61K 2039/5158 Antigen-pulsed cells, e.g. T-cells
• CPC Class Codes: A61K 2239/57 Skin; melanoma
• CPC Class Codes: A61K 35/12 Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells vaccines or medicinal preparations containing antigens or antibodies 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 39/46449 Melanoma antigens
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 15/00 Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/04 specific for metastasis
• CPC Class Codes: C12N 2501/05 Adjuvants
• CPC Class Codes: C12N 2501/056 Immunostimulating oligonucleotides, e.g. CpG
• CPC Class Codes: C12N 2501/2302 Interleukin-2 (IL-2)
• CPC Class Codes: C12N 2501/50 Cell markers; Cell surface determinants
• CPC Class Codes: C12N 2501/998 Proteins not provided for elsewhere
• CPC Class Codes: C12N 2501/999 Small molecules not provided for elsewhere
• CPC Class Codes: C12N 5/0636 T lymphocytes
• CPC Class Codes: G01N 33/505 involving T-cells

Abstract

Disclosed are compositions and methods for ex vivo expansion of tumorinfiltrating lymphocytes for use in adoptive cell therapy (ACT). Also disclosed are compositions and method for identifying an agent for ex vivo expansion of tumorinfiltrating lymphocytes for use in ACT. Also disclosed are methods for treating cancer using tumor-infiltrating lymphocytes expanded by the disclosed methods.

Claims

1. A method for ex vivo expansion of tumor-infiltrating lymphocytes for use in adoptive cell therapy (ACT), comprising culturing the lymphocytes to produce expanded lymphocytes in a culture medium comprising a toll like receptor (TLR) agonist in an amount effective to improve the tumor-specificity of the expanded lymphocytes.

3. The method of claim 1, wherein the TLR agonist is a ligand for a TLR selected from the group consisting of TLR1, TLR2, TLR3, TLR4, and TLR9.

4. The method of claim 1, wherein the TLR agonist comprises a ligand selected from the group consisting of Pam3CSK4, Pam3CSK4, poly I:

C, Ribomunyl, and CpG ODN.

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

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

7. The method of claim 1, wherein the cancer is metastatic.

8. The method of claim 1, wherein the cancer is recurrent.

9. The method of claim 1, wherein the subject is a human.

2. A method for treating cancer in a subject comprising the steps of:

a) obtaining autologous tumor-infiltrating lymphocytes from the subject,

b) culturing the lymphocytes in a culture medium comprising a toll like receptor (TLR) agonist to produce expanded lymphocytes,

c) treating the subject with nonmyeloablative lymphodepleting chemotherapy, and

d) administering the expanded lymphocytes to the mammal.

10. A method for identifying an agent for ex vivo expansion of tumor-infiltrating lymphocytes for use in adoptive cell therapy (ACT), comprising

contacting tumor-infiltrating lymphocytes with a candidate peptide or peptidomimetic from a peptide or peptidomimetic library for the ability to selectively bind the tumor-infiltrating lymphocytes;

and

screening the effect of binding peptide or peptidomimetic on the proliferation of the tumor-infiltrating lymphocytes,

wherein identification of a candidate peptide or peptidomimetic that increases proliferation of the tumor-infiltrating lymphocytes identifies an agent for ex vivo expansion of tumor-infiltrating lymphocytes for use in ACT.

13. The method of claim 10, wherein the peptidomimetic is a peptoid or peptide-peptoid hybrid.

14. The method of claim 13, wherein the peptoid or peptide-peptoid hybrid is stabilized by a hydrocarbon staple.

11. A method for ex vivo expansion of tumor-infiltrating lymphocytes for use in adoptive cell therapy (ACT), comprising culturing the lymphocytes to produce expanded lymphocytes in a culture medium comprising a peptide or peptidomimetic.

12. The method of claim 11, wherein the peptide or peptidomimetic is identified by the method of claim 9.