Transfected T-cells and T-cell receptors for use in immunotherapy against cancers
The present description relates to T-cell receptors (TCRs) binding to tumor-associated antigens (TAAs) for targeting cancer cells, T-cells expressing same, methods for producing same, and methods for treating cancers using same. In particular, the present description relates to TCRs and their variants that bind to HLA class I or II molecules with a peptide, such as IGF2BP3-001 have the amino acid sequence of KIQEILTQV (SEQ ID NO:1). The present description further relates to peptides, proteins, nucleic acids and cells for use in immunotherapeutic methods. In particular, the present description relates to the immunotherapy of cancer. The present description furthermore relates to tumor-associated T-cell peptide epitopes, alone or in combination with other tumor-associated peptides that can for example serve as active pharmaceutical ingredients of vaccine compositions that stimulate anti-tumor immune responses, or to stimulate T-cells ex vivo and transfer into patients. Peptides bound to molecules of the major histocompatibility complex (MHC), or peptides as such, can also be targets of antibodies, soluble T-cell receptors, and other binding molecules.
1. A method of treating a patient who has cancer that presents on the cell surface a peptide consisting of the amino acid sequence of KIQEILTQV (SEQ ID NO: 1) in complex with HLA-A*02, comprising administering to the patient a population of transformed CD8+ T cells expressing at least one vector encoding a T cell receptor (TCR),
wherein the TCR comprises SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 13, SEQ ID NO: 14, and SEQ ID NO: 15,
wherein the TCR is capable of binding to a peptide consisting of the amino acid sequence of KIQEILTQV (SEQ ID NO: 1) in a complex with HLA-A*02, and
wherein the cancer is selected from non-small cell lung cancer, small cell lung cancer, renal cell cancer, glioblastoma, gastric cancer, colorectal cancer, hepatocellular cancer, pancreatic cancer, chronic lymphocytic leukemia, acute myeloid leukemia, non-Hodgkin's lymphoma, melanoma, ovarian cancer, uterine cancer, and esophageal cancer.
2. The method of claim 1 , wherein the population of transformed CD8+ cells are produced by a method comprising
isolating a CD8+ cell from a subject,
transforming the isolated cell with at least one vector encoding the TCR to produce a transformed cell, and
expanding the transformed cell to produce the population of transformed CD8+ cells.
3. The method of claim 2 , wherein the subject is the patient.
4. The method of claim 2 , wherein the subject is a healthy donor.
5. The method of claim 1 , wherein the TCR comprises an α chain comprising the amino acid sequence of SEQ ID NO: 2 and a β chain comprising the amino acid sequence of SEQ ID NO: 10.
6. The method of claim 1 , wherein the population of transformed cells are administered in the form of a pharmaceutical composition.
7. The method of claim 6 , wherein the pharmaceutical composition comprises a therapeutically active agent selected from the group consisting of a radionuclide, a chemotherapeutic agent, and a toxin.
8. The method of claim 1 , wherein the TCR comprises:
a CDR1α chain comprising the amino acid sequence of SEQ ID NO: 5,
a CDR2α chain comprising the amino acid sequence of SEQ ID NO: 6,
a CDR3α chain comprising the amino acid sequence of SEQ ID NO: 7,
a CDR1β chain comprising the amino acid sequences of SEQ ID NO: 13,
a CDR2β chain comprising the amino acid sequence of SEQ ID NO: 14, and
a CDR3β chain comprising the amino acid sequence of SEQ ID NO: 15.
9. The method of claim 1 , wherein the TCR comprises:
a CDR1α chain consisting of the amino acid sequence of SEQ ID NO: 5,
a CDR2α chain comprising the amino acid sequence of SEQ ID NO: 6,
a CDR3α chain comprising the amino acid sequence of SEQ ID NO: 7,
a CDR1β chain consisting of the amino acid sequences of SEQ ID NO: 13,
a CDR2β chain comprising the amino acid sequence of SEQ ID NO: 14, and
a CDR3β chain comprising the amino acid sequence of SEQ ID NO: 15.
10. The method of claim 1 , wherein the TCR comprises:
a CDR1α chain comprising the amino acid sequence of SEQ ID NO: 5,
a CDR2α chain consisting of the amino acid sequence of SEQ ID NO: 6,
a CDR3α chain comprising the amino acid sequence of SEQ ID NO: 7,
a CDR1β chain comprising the amino acid sequences of SEQ ID NO: 13,
a CDR2β chain consisting of the amino acid sequence of SEQ ID NO: 14, and
a CDR3β chain comprising the amino acid sequence of SEQ ID NO: 15.
11. The method of claim 1 , wherein the TCR comprises:
a CDR1α chain comprising the amino acid sequence of SEQ ID NO: 5,
a CDR2α chain comprising the amino acid sequence of SEQ ID NO: 6,
a CDR3α chain consisting of the amino acid sequence of SEQ ID NO: 7,
a CDR1β chain comprising the amino acid sequences of SEQ ID NO: 13,
a CDR2β chain comprising the amino acid sequence of SEQ ID NO: 14, and
a CDR3β chain consisting of the amino acid sequence of SEQ ID NO: 15.
12. The method of claim 1 , wherein the TCR comprises:
a CDR1α chain consisting of the amino acid sequence of SEQ ID NO: 5,
a CDR2α chain consisting of the amino acid sequence of SEQ ID NO: 6,
a CDR3α chain comprising the amino acid sequence of SEQ ID NO: 7,
a CDR1β chain consisting of the amino acid sequences of SEQ ID NO: 13,
a CDR2β chain consisting of the amino acid sequence of SEQ ID NO: 14, and
a CDR3β chain comprising the amino acid sequence of SEQ ID NO: 15.
13. The method of claim 1 , wherein the TCR comprises:
a CDR1α chain consisting of the amino acid sequence of SEQ ID NO: 5,
a CDR2α chain comprising the amino acid sequence of SEQ ID NO: 6,
a CDR3α chain consisting of the amino acid sequence of SEQ ID NO: 7,
a CDR1β chain consisting of the amino acid sequences of SEQ ID NO: 13,
a CDR2β chain comprising the amino acid sequence of SEQ ID NO: 14, and
a CDR3β chain consisting of the amino acid sequence of SEQ ID NO: 15.
14. The method of claim 1 , wherein the TCR comprises
a CDR1α chain comprising the amino acid sequence of SEQ ID NO: 5,
a CDR2α chain consisting of the amino acid sequence of SEQ ID NO: 6,
a CDR3α chain consisting of the amino acid sequence of SEQ ID NO: 7,
a CDR1β chain comprising the amino acid sequences of SEQ ID NO: 13,
a CDR2β chain consisting of the amino acid sequence of SEQ ID NO: 14, and
a CDR3β chain consisting of the amino acid sequence of SEQ ID NO: 15.
15. The method of claim 1 , wherein the TCR comprises
a CDR1α chain consisting of the amino acid sequence of SEQ ID NO: 5,
a CDR2α chain consisting of the amino acid sequence of SEQ ID NO: 6,
a CDR3α chain consisting of the amino acid sequence of SEQ ID NO: 7,
a CDR1β chain consisting of the amino acid sequences of SEQ ID NO: 13,
a CDR2β chain consisting of the amino acid sequence of SEQ ID NO: 14, and
a CDR3β chain consisting of the amino acid sequence of SEQ ID NO: 15.
16. The method of claim 1 , wherein the cancer is glioblastoma.
17. The method of claim 1 , wherein the cancer is hepatocellular cancer.
18. The method of claim 1 , wherein the cancer is non-small cell lung cancer.
19. The method of claim 1 , wherein the cancer is non-Hodgkin's lymphoma.
20. The method of claim 1 , wherein the cancer is melanoma.