# US 10,478,481 B2 · Peptides and combination of peptides and scaffolds for use in immunotherapy against renal cell carcinoma (RCC) and other cancers

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- Number: US 10,478,481 B2
- Document ID: US10478481B2
- Status: Granted
- Kind: B2
- Application number: 16/415,753
- Filed: 2019-05-17
- Published: 2019-10-17
- Granted: 2019-11-19
- Earliest claimed: 2015-03-31
- Assignees: Immatics Biotechnologies GmbH
- Applicants: Immatics Biotechnologies GmbH
- Inventors: Andrea Mahr; Toni Weinschenk; Oliver Schoor; Jens Fritsche; Harpreet Singh; Colette Song
- Web page: https://patentgrep.com/patent/US10478481B2

## CPC

- C12N 5/0636: {T lymphocytes}
- A61K 35/17: Lymphocytes; B-cells; T-cells; Natural killer cells; Interferon-activated or cytokine-activated lymphocytes (when activated by a specific antigen A61K39/00)
- A61K 39/0011: {Cancer antigens}
- A61K 39/001102: {Receptors, cell surface antigens or cell surface determinants}
- A61K 39/001111: {Immunoglobulin superfamily}
- A61K 40/11: T-cells, e.g. tumour infiltrating lymphocytes [TIL] or regulatory T [Treg] cells; Lymphokine-activated killer [LAK] cells
- A61K 40/42: Cancer antigens
- A61P 35/00: Antineoplastic agents
- C07K 14/4748: {Tumour specific antigens; Tumour rejection antigen precursors [TRAP], e.g. MAGE}
- C07K 14/70539: {MHC-molecules, e.g. HLA-molecules}
- C07K 16/18: against material from animals or humans
- C07K 16/2833: {against MHC-molecules, e.g. HLA-molecules}
- C07K 16/3038: {Kidney, bladder}
- C12N 5/0638: {Cytotoxic T lymphocytes [CTL] or lymphokine activated killer cells [LAK]}
- C12N 15/115: Aptamers, i.e. nucleic acids binding a target molecule specifically and with high affinity without hybridising therewith {; Nucleic acids binding to non-nucleic acids, e.g. aptamers}
- G16B 25/00: ICT specially adapted for hybridisation; ICT specially adapted for gene or protein expression
- G16B 25/10: Gene or protein expression profiling; Expression-ratio estimation or normalisation
- A61K 2035/124: {the cells being hematopoietic, bone marrow derived or blood cells}
- A61K 2039/505: {comprising antibodies}
- A61K 2039/572: {cytotoxic response}
- C07K 14/705: Receptors; Cell surface antigens; Cell surface determinants {(tumour specific antigens C07K14/4748)}
- C07K 2317/73: Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
- C07K 2317/76: Antagonist effect on antigen, e.g. neutralization or inhibition of binding
- C07K 2319/33: fusions for targeting to specific cell types, e.g. tissue specific targeting, targeting of a bacterial subspecies
- C07K 2319/55: containing a fusion with a toxin, e.g. diphteria toxin
- C12N 2310/16: Aptamers
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00)
- G16B: BIOINFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR GENETIC OR PROTEIN-RELATED DATA PROCESSING IN COMPUTATIONAL MOLECULAR BIOLOGY

## Abstract

The present invention relates to peptides, proteins, nucleic acids and cells for use in immunotherapeutic methods. In particular, the present invention relates to the immunotherapy of cancer. The present invention 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.

## Claims

### Claim 1

A method of eliciting an immune response in a patient who has cancer, comprising administering to said patient a population of activated T cells that selectively recognize cells that aberrantly express a peptide consisting of the amino acid sequence selected from SEQ ID NOs: 58-60, 93, and 96;
wherein said cancer is selected from the group consisting of kidney cancer (RCC), lung cancer, brain cancer, stomach cancer, colon or rectal cancer, liver cancer, pancreatic cancer, prostate cancer, leukemias, breast cancer, melanoma, ovarian cancer, and esophageal cancer.

### Claim 2 (depends on 1)

The method of claim 1, wherein the T cells are autologous to the patient.

### Claim 3 (depends on 1)

The method of claim 1, wherein the T cells are obtained from a healthy donor.

### Claim 4 (depends on 1)

The method of claim 1, wherein the T cells are obtained from tumor infiltrating lymphocytes or peripheral blood mononuclear cells.

### Claim 5 (depends on 1)

The method of claim 1, wherein the activated T cells are expanded in vitro.

### Claim 6 (depends on 1)

The method of claim 1, wherein the population of activated T cells are administered in the form of a composition.

### Claim 7 (depends on 6)

The method of claim 6, wherein the composition further comprises an adjuvant.

### Claim 8 (depends on 7)

The method of claim 7, wherein the adjuvant is selected from anti-CD40 antibody, imiquimod, resiquimod, GM-CSF, cyclophosphamide, sunitinib, bevacizumab, interferon-alpha, interferon-beta, CpG oligonucleotides and derivatives, poly-(I:C) and derivatives, RNA, sildenafil, particulate formulations with poly(lactide co-glycolide) (PLG), virosomes, interleukin (IL)-1, IL-2, IL-4, IL-7, IL-12, IL-13, IL-15, IL-21, and IL-23.

### Claim 9 (depends on 1)

The method of claim 1, wherein the activated T cells are cytotoxic T cells produced by contacting T cells with an antigen presenting cell that expresses the peptide in a complex with an MHC class I molecule on the surface of the antigen presenting cell, for a period of time sufficient to activate said T cell.

### Claim 10 (depends on 9)

The method of claim 9, wherein the antigen presenting cell is infected with a recombinant virus expressing the peptide.

### Claim 11 (depends on 10)

The method of claim 10, wherein the antigen presenting cell is a dendritic cell or a macrophage.

### Claim 12 (depends on 5)

The method of claim 5, wherein the expansion is in the presence of an anti-CD28 antibody and IL-12.

### Claim 13 (depends on 1)

The method of claim 1, wherein the population of activated T cells comprises CD8-positive cells.

### Claim 14 (depends on 9)

The method of claim 9, wherein the contacting is in vitro.

### Claim 15 (depends on 1)

The method of claim 1, wherein the cancer is kidney cancer (RCC).

### Claim 16 (depends on 1)

The method of claim 1, wherein the immune response is capable of killing cancer cells that present a peptide consisting of the amino acid sequence selected from the group consisting of SEQ ID NOs: 58-60, 93, and 96.

### Claim 17

A method of treating a patient who has cancer, comprising administering to said patient a population of activated T cells that selectively recognize cells that aberrantly express a peptide consisting of the amino acid sequence selected from SEQ ID NOs: 58-60, 93, and 96;
wherein said cancer is selected from the group consisting of kidney cancer (RCC), lung cancer, brain cancer, stomach cancer, colon or rectal cancer, liver cancer, pancreatic cancer, prostate cancer, leukemias, breast cancer, melanoma, ovarian cancer, and esophageal cancer.

### Claim 18 (depends on 17)

The method of claim 17, wherein the population of activated T cells comprises CD8-positive cells.

### Claim 19 (depends on 17)

The method of claim 17, wherein the activated T cells are cytotoxic T cells produced by contacting T cells with an antigen presenting cell that expresses the peptide in a complex with an MHC class I molecule on the surface of the antigen presenting cell, for a period of time sufficient to activate said T cell.

### Claim 20 (depends on 19)

The method of claim 19, wherein the contacting is in vitro.

### Claim 21 (depends on 1)

The method of claim 1, wherein the peptide consists of the amino acid sequence of SEQ ID NO: 58.

### Claim 22 (depends on 1)

The method of claim 1, wherein the peptide consists of the amino acid sequence of SEQ ID NO: 59.

### Claim 23 (depends on 1)

The method of claim 1, wherein the peptide consists of the amino acid sequence of SEQ ID NO: 60.

### Claim 24 (depends on 1)

The method of claim 1, wherein the peptide consists of the amino acid sequence of SEQ ID NO: 93.

### Claim 25 (depends on 1)

The method of claim 1, wherein the peptide consists of the amino acid sequence of SEQ ID NO: 96.

### Claim 26 (depends on 17)

The method of claim 17, wherein the peptide consists of the amino acid sequence of SEQ ID NO: 58.

### Claim 27 (depends on 17)

The method of claim 17, wherein the peptide consists of the amino acid sequence of SEQ ID NO: 59.

### Claim 28 (depends on 17)

The method of claim 17, wherein the peptide consists of the amino acid sequence of SEQ ID NO: 60.

### Claim 29 (depends on 17)

The method of claim 17, wherein the peptide consists of the amino acid sequence of SEQ ID NO: 93.

### Claim 30 (depends on 17)

The method of claim 17, wherein the peptide consists of the amino acid sequence of SEQ ID NO: 96.