Proteome-based Immunotherapy of Brain Metastases From Breast Cancer

Summary

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.

Conditions

• Neoplasm Metastasis

Interventions

BIOLOGICAL

Dendritic vaccine, allogeneic hematopoietic stem cells, cytotoxic lymphocytes

BIOLOGICAL

Dendritic vaccine, autologous hematopoietic stem cells, cytotoxic lymphocytes

Sponsors & Collaborators

• Blokhin's Russian Cancer Research Center

  collaborator OTHER

• Russian Foundation of Technological Development

  collaborator OTHER

• The Serbsky State Scientific Center for Social and Forensic Psychiatry

  collaborator OTHER

• National Institute of Regenerative Medicine

  collaborator OTHER

• SRC Bioclinicum

  collaborator INDUSTRY

• NeuroVita Clinic

  lead OTHER

Principal Investigators

• Andrey S. Bryukhovetskiy, MD · ZAO "NeuroVita Clinic of Interventional and Restorative Neurology and Therapy"

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

70 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2012-12-31

Primary Completion

2018-12-31

Completion

2020-12-31

Countries

• Russia

Study Locations