Antitumor dendritic vaccines and cytotoxic lymphocytes.
The antitumor cell products based on the dendritic cells are known as dendritic vaccines (DVs) and model the acquired anti-tumor immunity. These cell products are obtained in the two stages of culturing of the patient’s own white blood cells (WBCs) with Il-2 and then with the dead tumor tissue that has been removed from the patient during the surgery. The first stage turns WBCs into dendritic cells and at the second sage the dendritic cells “eat” the tumor-specific proteins from tumor tissue, become a billboard for blood lymphocytes and demonstrate it as the antigen target to be eliminated. The dendritic cells that have absorbed tumor antigens from the tumor tissue start to present these tumor antigens on the cell surface for the specific cytotoxic T lymphocytes (CTLs) that will recognize such antigen presenting cells and eliminate them. To enhance the tumor antigen presentation, the proteomic mapping of the tumor cells by mass-spectrometry detects the dominating tumor-specific proteins and the artificially received dominating tumor antigens represented by recombinant proteins are “fed” to the dendritic cells. That is, the tumor specific proteins with the highest expression are detected and their recombinant analogues enhance the anti-tumor characteristics of the dendritic cells. These vaccines are named proteome-based as they are enhanced by the individual tumor specific proteins. To guarantee the emergence of the cytotoxic lymphocytes in the organism as the reaction to DVs, they also can be supplied in a prosthetic way by the culture of the leukapheresis product of the peripheral blood with tumor antigens presenting dendritic cells. As a result, the CTLs that are able to eliminate all tumor cells are cloned in vitro.
The DV and CTL based immunotherapy is much more efficient at the early stages of cancer and as the prevention measure. However, it is also very beneficial and even becomes the main anti-tumor agent when all others cannot be used due to the chemo- and radiotherapy damaged hemopoiesis and immunopoiesis. If the new method of the immunotherapy is used for stages II to IV, the disease transforms into chronic form and improves life quality. The survival median increases by two to three times. The patients receive the opportunity to keep their regular life style and the progress of the disease and metastases are prevented. The method is protected by the patent of the Russian Federation.
Practical effectiveness of these cell preparations has been already proven. So far, not all of them have been registered as the bylaws to the Federal law №180 FZ, 2016, have not been developed yet, but their efficiency is confirmed by the long-term use in the clinical practice. Our work on new preparations continues an as soon as the normative documents appear, the preparations will be approved. When the patients take part in the clinical research, they acquire no only improved quality of life but also the chance for survival.
Combined immunotherapy of chemotherapy resistant cancer cases or the cases with absolute or relative contraindications to surgical cytoreductive intervention, chemo- and radiotherapy.
Diseases include: all malignant neoplasms that are resistant to the administered chemotherapy, the patients with absolute and relative contraindications to cytoreductive surgical interventions, chemo- and radiotherapy (pace makers, artificial organs, severe ciliary arrhythmia, stage III circulation failure, severe diabetes mellitus and others).
Therapy principle: A malignant tumor is heterogeneous and consists of the tumor cells and the cells of microenvironment (macrophages, dendritic cells, lymphocytes) that constitute up to 80% of the neoplasm mass. The normal cells of the microenvironment protect the tumor cells from external factors, chemotherapy including. Also, they mask antigens on the surface of the malignant cells and reduce the effectiveness of the immunotherapy. When we administer autologous cytotoxic lymphocytes that have been isolated from the patient and underwent cell expansion in the presence antigen presenting cells loaded with tumor antigen, we are able to affect not only malignant cells but also the cells of microenvironment and induce apoptosis (cell death). Being deprived of the support and protective effect of the microenvironment, a resistant tumor frequently becomes sensitive, and sometimes even to the chemotherapy, to which it was initially resistant. It takes two to three weeks to prepare the immune product, which must be taken into account if using this approach in resistant and progressing cases.
Result: Increased survival rates of the chemotherapy resistant cases by 1.5-2 times and alternative cytotoxic and cytostatic therapy of the patients with contraindications to the surgery, chemo- and radiotherapy.
