Individualized vaccines for cancer

Patent metadata

Field	Value
Publication number	US-11248264-B2
Application number	US-202016920286-A
Country	US
Kind code	B2
Filing date	Jul 2, 2020
Priority date	May 24, 2011
Publication date	Feb 15, 2022
Grant date	Feb 15, 2022

Abstract

The present invention relates to the provision of vaccines which are specific for a patient's tumor and are potentially useful for immunotherapy of the primary tumor as well as tumor metastases. In one aspect, the present invention relates to a method for providing an individualized cancer vaccine comprising the steps: (a) identifying cancer specific somatic mutations in a tumor specimen of a cancer patient to provide a cancer mutation signature of the patient; and (b) providing a vaccine featuring the cancer mutation signature obtained in step (a). In a further aspect, the present invention relates to vaccines which are obtainable by said method.

First claim

The invention claimed is:

1. A method for treating cancer by:
administering to an individual with a tumor an individualized cancer vaccine comprising RNA encoding a recombinant polyepitopic polypeptide, wherein the polypeptide comprises two or more immunogenic neo-epitopes identified from a sample comprising tumor cells from the individual, wherein each immunogenic neo-epitope is characterized by each of the following characteristics:
(i) occurs in a transcript;
(ii) occurs in a protein-coding region;
(iii) introduces a change in amino acid sequence; and
(iv) is predicted to exhibit WIC binding;

wherein following the administration, the individualized cancer vaccine elicits a T cell response against the tumor of the individual.

2. The method of claim 1 , wherein the individualized cancer vaccine was produced by a process comprising steps of:
(a) obtaining nucleic acid sequence information from a sample comprising tumor cells from the individual;
(b) obtaining nucleic acid sequence information from a sample comprising non-tumor cells from the same individual;
(c) comparing the tumor cell sequence information with the non-tumor-cell sequence information so that somatic mutations present in the tumor cell sequence information are identified;
(d) classifying as immunogenic neo-epitopes at least two of the identified somatic mutations characterized by each of the characteristics; and
(e) producing a nucleic acid vaccine comprising RNA encoding a recombinant polyepitopic polypeptide, wherein the polypeptide comprises two or more immunogenic neo-epitopes identified in steps (a)-(d) and the neo-epitopes are fused together by peptide bonds or linkers.

3. The method of claim 2 , wherein the step of obtaining nucleic acid sequence information from the sample comprising tumor cells from the individual comprises single cell sequencing of one or more tumor cells from the individual.

4. The method of claim 3 , wherein the tumor cells are or comprise circulating tumor cells.

5. The method of claim 2 , wherein the tumor cell and/or non-tumor-cell sequence information is or comprises genomic, transcriptome, and/or exome sequence information.

6. The method of claim 1 , wherein the recombinant polyepitopic polypeptide encoded by the RNA comprises 10 or more neo-epitopes.

7. The method of claim 1 , wherein the recombinant polyepitopic polypeptide encoded by the RNA further comprises one or more epitopes that are expressed by that individual's tumor, which epitopes do not contain the tumor-specific somatic mutation(s) of the neo-epitopes.

8. The method of claim 1 , wherein RNA encoding a vaccine sequence of each neo-epitope is or comprises a RNA sequence encoding (i) respective somatic mutation(s) and (ii) its epitope flanking regions as present in a respective naturally occurring protein.

9. The method of claim 8 , wherein the vaccine sequence of each neo-epitope encoded by the RNA comprises 20 or more amino acids.

10. The method of claim 1 , wherein the neo-epitopes encoded by the RNA are arranged in a head-to-tail configuration.

11. The method of claim 1 , wherein the RNA encoding the recombinant polyepitopic polypeptide comprises a linker sequence between each of the encoded neo-epitopes.

12. The method of claim 11 , wherein the linker sequence encodes a peptide linker characterized in that at least 60% of amino acids of the peptide linker are glycine and serine residues.

13. The method of claim 1 , wherein one or more of the neo-epitopes comprises at least one primary basal mutation.

14. The method of claim 2 , wherein the nucleic acid sequence information from the sample comprising non-tumor cells is obtained from genomic germline DNA from peripheral blood mononuclear cells (PBMCs).

15. The method of claim 1 , wherein the RNA comprises:
an unmasked poly-A sequence; a 3′-non translated region (UTR); an MHC class I signal peptide fragment and transmembrane and cytosolic domains including the stop codon; a 5′ cap; or combinations thereof.

16. The method of claim 1 , wherein the RNA comprises an unmasked poly-A sequence having a length of approximately 120 adenosine residues.

17. The method of claim 1 , wherein the RNA comprises a 5′ cap that is or comprises:

wherein R 1 and R 2 are independently hydroxy or methoxy, and W, X, and Y are independently oxygen, sulfur, selenium or BH 3 .

18. The method of claim 17 , wherein the 5′ cap is or comprises m 2 7,2′-O Gpp s pG.

19. The method of claim 1 , wherein the individualized cancer vaccine is administered in combination with a cancer therapeutic regimen.

Assignees

• Tron Translationale Onkologie An Der Univ Der Johannes Gutenberg Univ Mainz Ggmbh
• BioNTech SE

Inventors

• Sahin Ugur
• Kreiter Sebastian
• Diken Mustafa
• Diekmann Jan
• Koslowski Michael
• Britten Cedrik
• Castle John Christopher
• Löwer Martin
• Renard Bernhard
• Omokoko Tana
• De Graaf Johannes Hendrikus

Classifications

• A61K39/00

  Medicinal preparations containing antigens or antibodies (materials for immunoassay G01N33/53) · CPC title

• A61K39/0011 Primary

  Cancer antigens · CPC title

• C12Q1/6886

  for cancer (immunoassay for cancer G01N33/575) · CPC title

• C12Q1/6881

  for tissue or cell typing, e.g. human leukocyte antigen [HLA] probes · CPC title

• C12Q1/6874

  involving nucleic acid arrays, e.g. sequencing by hybridisation · CPC title