Cell Immunotherapy of Cancer
ALLOGENEIC ADOPTIVE IMMUNOTHERAPY OF MALIGNANCIES WITH THE COMPLEX PREPARATION OF THE BONE MARROW PRECURSORS AND THE CELLS OF THE INNATE IMMUNITY (NK CELLS, TCR Ɣ/∂ CELL AND B1-CELLS)
The project is aimed at the development of the innovative anti-tumor biotherapeutic technologies and biomedical cell products that can provide for the cure and/or prevention of the metastases of various malignancies. The unique experimental and clinical research of the team of Professor Nikolay Trapeznikov in 1982-1993 is used as the basis of the project. Using the principle of partial histocompatibility and alloreactivity of the bone marrow of the donor and host, the Russian scientists studied the immunological phenomena of the graft versus tumor effect and graft versus host effect that emerge after allogeneic transplantation of the bone marrow in cancer cases. The pioneering research of the Russian scientists and their novel results of the cancer therapy have been forgotten due to the USSR breakup, social-economic crises and premature death of the academician of the Russian Academy of Sciences and Russian Academy of Medical Sciences, Prof. Nikolay Trapeznikov.
Currently, due to the efforts of Prof. Mikhail Davydov and Trapeznikov’s former students, the research has been renewed and new evidence of immunology and cancer biology is incorporated. The project studies allogeneic adoptive immunotherapy (alloAIT) from the new molecular-biological standing point of contemporary oncology.
Usually, after the standard high-dose chemotherapy, the complete replacement of the cells of immune system is planned, but according to the project the cells of immune surveillance are only partially replaced by bone marrow precursors and the cells of innate immunity (allogeneic NK cells, TCR ɣ/∂ cell and B1-cells). These cells are active against the tumors when the donor and the host are incompatible by haplotypes, by the HLA calls I products, by KIR receptors on the NK cells and compatible by HLA class II along with the maximal expression of KIR receptors on the donor NK cells. In these cases we should not achieve complete histocompatibility but use related haploidentical compatibility of the host and the donor.
In the case of alloAIT, the less hard regimens of chemotherapy can be used. They initially imply the development of the mixed (chimeric) hemopoiesis, and namely, the effect of the graft versus tumor along with lesser number of complications. In this case the anti-tumor therapy will be more of immunotherapy kind and the cell transplantations can be combined with standard protocols of chemotherapy. In the course of the alloAIT the cancer patient receives the combined allogeneic biomedical cell product that contains the bone marrow precursors and the cells of innate immunity (allogeneic NK cells, TCR ɣ/∂-cells and B1-cells). They provide for further development of the anti-tumor immune response manifested in the elimination of the residual cancer cells. If the symptoms of the graft versus host disease appear, they are controlled by the hematologists-transplantologists with no risk to patient’s life
The best donor/host pair for the alloAIT is achieved through the partial HLA-compatibility of the main complex of the histocompatibility of class I and II, compatibility by the blood group, Rh factor and mismatch of the repertoire of KIR-receptors of the NK-cells and markers of T-lymphocytes of blood. The alloAIT implies the administration of the biomedical cell product, and the result is followed up for five years. The proposed alloAIT is an alternative component of the anti-cancer therapy that replaces or supplements chemotherapy and/or radiotherapy in the cancer cases with high risk of progress or for metastases prevention.