THE EFFECTIVENESS OF COMBINED USE OF IMMUNO- AND CHEMOTHERAPY WITH DIFFERENT METASTATIC POTENTIAL TUMORS


I.M. Voyeykova, N.L. Cheremshenko, A.V. Chumak, T.V. Symchych, О.М. Karaman, N.I. Fedosova

R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology of NAS of Ukraine, Kyiv, Ukraine

DOI: https://doi.org/10.15407/oncology.2023.04.262

Summary. Aim:  to assess the effectiveness of the combined use of immune and chemotherapy with different metastatic tumors. Object and methods: two experimental models were used: Ehrlich adenocarcinoma (ACE) and Lewis lung carcinoma (CLL). As a means of chemotherapy used cisplatin, biotherapy – B. subtilis IMB B-7724 lectin, which in low concentrations has immunostimulating activity. Animals of different groups were introduced in mono-mode or theіr combination. The standard tumor growth and metastasis rates were evaluated. Upon completion of treatment, the activity of nonspecific immunity effectors was evaluated. The statistical analysis of the results was performed according to the generally accepted methods of variation statistics. Results: on both models of tumor growth, antitumor and antimetastatic efficacy is demonstrated as a means of immunotherapy of B. subtilis IMB B-7724 lectin. The severity of the effect depended on the mode of its introduction (mono-mode, combination with chemotherapy) and model tumors: for mice with ACE more effective was the introduction of lectin in mono-mode (the tumor growth index, TGI=53,2%); with LLC – combined injection of lectin and cisplatin (TGI =46,5%, metastasization inhibition index, МІІ=78,6%). The effect in both cases is associated with the ability of the lectin to remodel and maintain for a long time on the background of tumor growth polarization of macrophages in the direction of the proinflammatory state of M1 (increase in production of NO against the background of reduction of arginase activity (ARG)). This is evidenced by a strong positive correlation between NO/ARG and TGI level (r = 0.90, p <0.05 (ACE); also between NO/ARG and IIM level (r = 0.98, p <0.05 (CLL)). Conclusions: antitumor and antimetastatic efficiency of various regimens of use of chemo-/immunotherapy is due to the activation of nonspecific immune response and depends on both the immunogenic characteristics of tumors and on the initial physiological features of the immune system.

Keywords: Ehrlich adenocarcinoma, Lewis lung carcinoma, lectin, cisplatin, antitumor activity, antimetastatic activity

 

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