Class I and class II HLA tumor antigen peptides for treatment of breast/breast cancer

A tumor antigen peptide, breast cancer technology, applied in the direction of cancer antigen components, breast cancer vaccines, anti-tumor drugs, etc., can solve the problem of not being applicable to other patients with the same tumor

Pending Publication Date: 2022-03-22
PMCR GMBH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0017] Therefore, in principle, these novel vaccines for cancer immunotherapy should not be administered to other patients with the same tumor, but only to a single patient whose mutational group was previously analyzed for vaccine production

Method used

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  • Class I and class II HLA tumor antigen peptides for treatment of breast/breast cancer
  • Class I and class II HLA tumor antigen peptides for treatment of breast/breast cancer
  • Class I and class II HLA tumor antigen peptides for treatment of breast/breast cancer

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0361] Example 1: Transcriptome analysis [mRNA expression]

[0362] Transcriptome analysis (sequencing) was performed on all patients using the PANTHER array analysis (44K array) from Agilent Technologies. The 44K chip used contained 44,000 gene probes, so in each case, each patient could be analyzed with the chip for the activity of more than 34,000 gene expression markers. In each case, 1000 genes with a 10-fold increase in association were identified.

[0363] Assessments were based on published gene signatures known to experts.

Embodiment 2

[0364] Example 2: EXOM sequencing

[0365] Exome sequencing is performed on standard frozen specimens from patients with tumor DNA extracted. Next-generation sequencing of the exome was performed from tumor samples, covering more than 95% of the entire human coding exonic region. To this end, more than 290,000 relevant sections of DNA were selectively amplified and sequenced by semiconductor sequencing technology, among other things.

[0366] The purpose of the analysis was to identify possible mutations in order to design individual tumor antigen peptide immunizations. To exclude germline non-tumor-associated variants (SNPs, single nucleotide polymorphisms), DNA was simultaneously isolated from nucleated blood cells of the patients and sequenced using the same method for comparison. Differentiation of potential neoantigen candidates proceeds through the following six steps:

[0367] 1) Reduced selection for tumor / somatic mutations by excluding non-tumor-specific polymorphi...

Embodiment 3

[0392] Example 3: Patient with mMC (metastatic breast cancer), type_HER2-neu

[0393] 1) The clinical history of the patient

[0394] patient, female

[0395] preliminary clinical findings : Invasive ductal bifocal breast cancer (breast CA), right side, tumor 2cm to 5cm maximum (pT2), pN1sn pN1(3 / 5)G2, NO, ER-, PR-, HER-2neu:3+, Ki-67: 55%.

[0396] Treatment procedure:

[0397] After 2 weeks: 6 cycles of neoadjuvant chemotherapy (TCH w3), trastuzumab;

[0398] ■After 6 months: irradiate the right breast + lymphatic drainage area (LAG).

[0399] The tumor was completely destroyed by radiotherapy or chemotherapy (CR=complete remission), and the result: the patient was cured and discharged.

[0400] relapse : local recurrence with additional liver metastases (4 lesions) occurred 24 months after initial diagnosis; results: ER-, PR+ (60%), HER-2neu: 3+, Ki-67: 80%.

[0401] This recurrent breast / mammary CA was accompanied by liver metastases and was significantly more ...

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PUM

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Abstract

The present invention relates to a pharmaceutical composition for the treatment or prevention of breast cancer / breast cancer, in particular locally recurrent or metastatic breast cancer, in a patient or group of patients suffering from or suspected of suffering from breast cancer, comprising: at least 4 to 8 HLA-A tumor antigen peptides corresponding to the MHC class I complex and at least 2 tumor antigen peptides corresponding to the MHC class II complex, wherein the HLA tumor antigen peptide is a tumor-specific or tumor-associated HLA antigen peptide and is directed to at least one MHC complex, including combinations thereof; pharmaceutical compositions, kits (or portions thereof); methods of determining class I and / or class II HLA peptides; a process for preparing the pharmaceutical composition according to the invention; the invention also relates to application of the pharmaceutical composition in preparation of the pharmaceutical composition for treating malignant tumors, leukemia and tumors.

Description

technical field [0001] The invention relates to a pharmaceutical composition for treating or preventing breast cancer / breast cancer in a patient or patient group suffering from or suspected of having breast cancer / breast cancer, particularly locally recurrent or metastatic breast cancer / breast cancer, according to the present invention Process for the preparation of pharmaceutical compositions comprising at least 4 to 8 human leukocyte antigens (HLA) corresponding to MHC class I complexes, and methods for determining regression, progression or occurrence of breast cancer / breast cancer disease -A tumor antigen peptide (also referred to herein as "HLA-A restricted tumor antigen peptide") and at least 2 tumor antigen peptides corresponding to MHC class II complexes (also referred to herein as "HLA-restricted tumor antigen peptide" respectively) peptide", "HLA", "amino acid sequence of the present invention", "compound of the present invention" and "polypeptide of the present inve...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K39/00A61K39/395A61K38/08A61P35/00A61P15/14C07K14/74G01N33/574G01N33/68
CPCA61K39/0011A61K39/39558A61K38/08A61P35/00A61P15/14C07K14/70539G01N33/57415G01N33/68A61K2039/812A61K2300/00A61K38/10A61P15/00C07K7/02
Inventor 沃尔夫冈·舍恩哈尔廷西比尔·乌尔班
Owner PMCR GMBH
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