Proteome-based Immunotherapy of Brain Metastases From Breast Cancer

Trial Hypothesis: Acute, progressing lethal neurooncological process can be transferred into chronic and non-lethal, the survival rates and life quality can be improved by of control of tumor cells (TCs) quantity and targeted regulation of effector functions of tumor stem cells (TSCs). Brief Description: The first line therapy of brain metastases of breast cancer (BMBC) involves allogeneic haploidentical hematopoietic stem cells (HSCs), dendritic vaccine (DV) and cytotoxic lymphocytes (CTLs). TCs and TSCs are isolated from BMBC sample. Dendritic cells are isolated from peripheral blood mononuclear cells and cultured. Tumor sample provides tumor specific antigens to prepare DV. CTLs are obtained from peripheral blood after DV administrations. HSCs are harvested from closely related donor after granulocyte-colony-stimulating factor (G-CSF) administration. Allogeneic HSCs are administered intrathecally 5 times every 2 weeks, at day 1, 14, 28, 42, 56. DV is given 3 times every 2 weeks (day 14, 28, 42) subcutaneously in four points. CTLs are administered every 2 weeks for 3 months, then 3 times every 1 month intrathecally. Six months after the therapy completion, the efficiency is evaluated and the cohort demonstrating efficiency continues the therapy, while cohort demonstrating no efficiency is transferred to active comparator arm. Second line therapy involves DV with recombinant proteins, CTLs and autologous HSC with modified proteome. Autologous HSCs are mobilized by G-CSF. Carcinogenesis-free intracellular pathways of signal transduction able to respond to targeted regulation of therapeutic cell systems with specific properties, are detected in TSCs using complete transcriptome profiling of gene expression, proteome mapping and profiling of proteins, bioinformation and mathematical analysis and mathematical modeling of protein profiles. To find key oncospecific proteins in TSCs and TCs, the targets for TSCs regulation are detected, as well as protein ligands able to regulate reproductive and proliferative properties of TSCs. Using these data of TCs and TSCs proteins, the cell preparations to initiate adoptive immune response are prepared: DV loaded with recombinant proteins analogous to key tumor antigens, CTLs and autologous proteome-based HSCs. Autologous HSCs, DV and CTLs are administered as in the first line therapy.

Sex

All

Minimum age

18 Years

Maximum age

70 Years

Inclusion Criteria:

* Morphologically confirmed breast cancer metastases to brain (in case of relapse and impossibility of biopsy, diagnosis based on radiological and other diagnostic methods)
* Brain metastases of breast cancer refractor to the 1-st and following conventional chemotherapies and radiotherapy, in case their removal is not possible
* Brain metastases of breast cancer relapses after no less than one course of conventional chemotherapy and radiotherapy in case their removal is not possible.
* Availability of HLA partially compatible related donor
* Life expectancy of no less than 3 months
* Absence of severe decompensated organ dysfunction
* Informed consent of the patient
* Informed consent of the donor

Exclusion Criteria:

* Failure to meet one of the inclusion criteria

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