Innovative cell immunotherapy of cancer:
ALLOGENIC ADOPTIVE IMMUNOTHERAPY OF CANCER BY THE COMPLEX PREPARATION OF BONE MARROW PRECURSORS AND CELLS OF THE INNATE IMMUNITY.
The project is already ten years old. It has been initiated by Professor Tupitsin NN of FGBU Blokhin NN Research Center of Oncology and it aims at the development of the novel anti-tumor biothherapeutic technologies and biomedical cell products (BMCPs) to treat and/or to prevent tumor relapses and metastases. The unique experimental and clinical research of Prof. NN Trapeznikov of 1982-1993 have been used as the basis for our project. Using the principles of partial histocompatibility and alloreacivity of the donor’s and host’s bone marrow, the researchers studied such immunological phenomena as graft-vs-tumor (GVT) effect and graft-versus-host disease (GVHD) that are observe after the allogenic transplantation of bone marrow in the patients. The pioneer research has been undeservingly forgotten after the collapse of the Soviet Union, social and economic crisis in the 90s and early death of the head of the team, Prof. NN Trapeznikov, the member of the Russian Academy of Science and the Russian Academy of Medical Science. Currently, thanks to the efforts of Prof. Trapeznikov followers and students and former head of the Blokhin NN Research Center of Oncology the research has been renewed at a new spiral of development of the scientific progress engaging new evidence of he immunology and biology of cancer.
This project considers allogenic adoptive Immunotherapy (alloIT) where the cells of the immune surveillance after high dose chemotherapy are partially replaced. NK, TCR ɣ/∂ and B1 cells are active against the tumors under specific mismatch of HLA and KIR receptors. In some cases, we do not aim at complete histocompatibility but use relative haploidentical compatibility of donor and host. AlloIT permits milder regimen of that imply the formation of the mixed, chimeric hemopoiesis. This, the anti-tumor therapy will be less transplantation and more like immunotherapy and in this case, the cell transplantations can be combined with standard protocols of chemotherapy. The AlloIT is performed by the transfusion of the allogenic combined BMCP that contains bone marrow precursors and cells of the innate immunity to initiate an anti-tumor immune response that eliminates residual tumor cells. In the case of GVHD, the symptoms are monitored and controlled.
The best haploidentical pair of the donor and host is selected by the specific match and mismatch of their HLA types, rhesus, KIR of NK cells and T cells of blood. The proposed AlloIT is a real alternative component of the anti-tumor therapy that can supplement or replace the chemo- and radiotherapy in cancer cases with high risk of progress.
Key words: alloreactivity, KIR, T cells, NK cells, TCR ɣ/∂ cells, B1 cells, solid tumors, bone marrow transplantation, immunotherapy
