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Personalized cancer vaccines and adoptive immune cell therapies

A cancer vaccine and cancer cell technology, applied in biochemical equipment and methods, cancer antigen components, medical raw materials derived from mammals, etc.

Inactive Publication Date: 2015-05-27
PERSIMMUNE
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] However, the identification of tumor antigens and their translation to immunotherapy still face many problems

Method used

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  • Personalized cancer vaccines and adoptive immune cell therapies
  • Personalized cancer vaccines and adoptive immune cell therapies
  • Personalized cancer vaccines and adoptive immune cell therapies

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0103] Example 1: Identification of cancer mutations from exome and transcriptome libraries using NGS

[0104] Figure 1a–c shows a schematic for identifying mutations in cancer cells that can be targeted for immune recognition. Leukemic cells (L) and Epstein-Barr virus transformed B cells (patient EBV cell line) (P) were obtained from patient #1 prior to hematopoietic stem cell transplantation (HSCT). Leukemic cells were isolated from blood (22, 27) and EBV cells were prepared using previously published methods (see, eg, Caputo JL et al., J. Tissue Culture Methods 13:39-44, 1991). EBV cell lines were similarly produced from bone marrow donors (D). Freeze cells in liquid nitrogen.

[0105] DNA exome preparation using NGS methods from Patient #1 Leukemia Cells, Patient #1 EBV Cell Line, and Donor EBV Cell Line under contract with Expression Analysis, Inc., Durham, NC library. RNA transcriptome libraries were prepared by Expression Analysis Inc. using patient leukemia cells...

Embodiment 2

[0118] Example 2: Selection of cancer-specific mutations with potential HLA-binding motifs

[0119] Further selections were performed on the mutation sets from L-seq1 and Lseq2 to identify smaller subgroups with the potential to bind cancer patient HLA antigens. To this end, each L-seq was assessed for mutations involving tyrosine gains or losses. For L-seq1, there were 15 sequences with tyrosine gains and 184 sequences with tyrosine deletions (Fig. 1b). Of the 127 sequences in L-seq2 from cancer cell expressed genes, there were 5 sequences with tyrosine gains and 10 sequences with tyrosine deletions (Fig. 2b).

[0120] Peptide sequences containing mutant sequences involving tyrosines (gains and deletions) and corresponding wild-type peptides (by in silico) were transcribed into 21-mer peptides containing 10 on both sides of the tyrosine-involving sites amino acid. This 21-mer peptide was then assessed to have an 8-11 amino acid epitope shown to bind HLA-A1 under the IEDB...

Embodiment 3

[0126] Example 3 : Identification of Cancer Mutations – Patient #2

[0127] A modified schematic for identifying mutations in cancer cells that can be used as targets for immune recognition was used for samples obtained from patient #2 and is shown in Figure 8a. Leukemic cells (L) and Epstein-Barr virus-transformed B cells (patient PHA cell line) (P) were obtained from patients before hematopoietic stem cell transplantation (HSCT). Leukemic cells were isolated from blood (22, 27) and EBV cells were prepared using previously published methods (see, eg, Caputo JL et al., J. Tissue Culture Methods 13:39-44, 1991). EBV cell lines were similarly generated from bone marrow donors (D). Freeze cells in liquid nitrogen.

[0128] DNA exome libraries were prepared using NGS methods from patient leukemia cells, patient EBV cell lines, and donor EBV cell lines under contract with Expression Analysis, Inc., Durham, NC. RNA transcriptome libraries were prepared by Expression Analysis In...

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Abstract

Cancer antigens containing mutations in an expressed gene of cancer cells from a cancer patient are identified. Sequences from cancer cells obtained using a parallel sequencing platform are selected by comparing to the patient's normal genes or to normal genes from an HLA-matched individual. Sequences are further selected by identifying an HLA supertype of the cancer patient and selecting for that HLA supertype, sequences that have a particular amino acid at the mutant position and / or corresponding wild-type position in the effected gene. Peptides containing cancer antigens (i.e., mutations—once a mutation is defined, what makes it an immunogen is its ability to induce an immune response) are optionally tested for binding to HLA antigens of the cancer patient. Peptides containing the cancer antigens are evaluated for activating T cells (e.g., helper T lymphocytes and cytotoxic T lymphocytes (CTL)) cell lines from the cancer patient or from an HLA-matched donor. The cancer antigen(s) identified for a cancer patient are used to prepare a cancer vaccine and to treat the cancer patient.

Description

[0001] Cross References to Related Applications [0002] This application claims the benefit of US Provisional Application 61 / 670,931, filed July 12, 2012, which is incorporated herein by reference. technical field [0003] The present invention relates to the identification of mutations in expressed genes of cancer cells from cancer patients and the use of the mutations in the preparation of cancer vaccines and adoptive immune cell therapy. Background of the invention [0004] Cancer is the second leading cause of death in the United States. It is estimated that in 2010, approximately 570,000 people will die from cancer and 1.5 million new cases will be diagnosed (1). For early-stage cancer (that has not spread to the lymph nodes and is non-metastatic), surgical removal is a very effective treatment. However, for more advanced cases, standard, non-specific cancer treatments (chemotherapy and radiation) are used. These treatments affect many healthy cells and lead to incr...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12Q1/68G16B20/20
CPCC12Q1/6881C12Q1/6888C12Q2535/122C12Q2600/156G16B20/00A61K39/0011A61P35/00G16B20/20A61K39/4611A61K35/17A61K39/4644C12Q1/6874G01N33/56977G01N2333/70539
Inventor M·A·维特耶罗
Owner PERSIMMUNE
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