Elaboration and pilot study of 3D vaccines for oncotherapy

Abstract

The purpose of the study was to study the possibility of using intracorporeal constructs in vivo with healthy or autologous dead tumor cells on porous extracellular matrix of titanium nickelide (PEMTN).We aimed to determine the advantage of the effect of this method on the change in the immunological status of cancer patients in comparison with patients receiving traditional treatment.The study used CBA and AKR JY mice and studied 10 patients with solid stage IV tumors of various localization (pancreas, intestines, lungs, ovary, head and neck) and 3 oncohematological patients (lymphoblastic lymphosarcoma, chronic myeloid leukemia (CML)).PEMTN was seeded with a suspension with bone marrow cells from CBA mice and cultured for 8 weeks in a long-term Dexter culture. It was shown that after 6 weeks of incubation of bone marrow cells on PEMNT in vitro, the proportion of bone marrow cells produced from the pores of the matrix into the liquid medium varied within 58–82%, which corresponded to the figures of the 1st week of incubation.After implantation of PEMTN with fetal liver cells in AKR/JY mice with spontaneous lympholeukemia, the implant successfully engrafted and after 30 days, no noticeable fluctuations in the leukocyte count were observed. After 3–4 weeks implantation, a 3-fold increase in the level of erythrocytes with fetal hemoglobin, which is not normally found in adult AKR/JY mice, was observed. There was also an increase (by 274%, p < 0.05) in the number of blood reticulocytes and a 26% decrease in the activity of the tumor process.In cancer patients with solid tumors, the level of SH-groups erythrocytes of blood increased 1.5–2.3 times 2 months after the implantation of hybrid oncotherapy implants carrying autologous apoptized tumor cells, treated in vitro. This implants, already 3–4 weeks after implantation in oncopatients, restored the blood system parameters.The most active (2–3 times) increased individual indicators of cellular immunity, in particular the number of NK cells, active (CD25+) and apoptotic lymphocytes (CD95+ marker). From the 3rd month of the study, the level of humoral immunity increased (immunoglobulins, circulating immune complexes). Clinically, the activation of immunity was accompanied by the stabilization of the process or a decrease in the volume and fragmentation of the primary nodes of solid tumors.In oncohematological patients, an increase in the CD95 marker in the peripheral cells of blood was observed.Therefore, in a patient with CML, the implantation, which followed therapy with low doses of cytostatics (myelosan, hydroxyurea) and the immune effect of the implantation, led to a 6-month hematological remission with normal values of the total number of leukocytes and leukocyte blood count. It has been shown that healthy cells in this matrix retain their viability and it allows them to multiply both in the in vitro system and in the in vivo system. The possibility of clinical use of PEMNT carrying autologous dead tumor cells treated in vitro with the aim of improving antitumor immunity, accelerating the recovery of blood counts in cancer patients and achieving partial remission has been shown.