Immunotherapy, which is seen as a major tool for cancer treatment, requires, in some cases, the presence of several agents to maximize its effects. Adjuvants can enhance the effect of other agents. However, despite their long-time use, only a few adjuvants are licensed today, and their use in cancer treatment is rare. Azoximer bromide, marketed under the trade name Polyoxidonium® (PO), is a copolymer of N-oxidized 1,4-ethylenepiperazine and (N-carboxyethyl)-1,4-ethylene piperazinium bromide. It has been described as an immune adjuvant and immunomodulator that is clinically used with excellent tolerance. PO is used in the treatment and prophylaxis of diseases connected with damage to the immune system, and there is interest in testing it in antitumor therapy. We show here that PO treatment for 1 week induced positive pathological changes in 6 out of 20 patients with breast cancer, including complete response in a triple-negative patient. This correlated with an increased tumor CD4+ T-lymphocyte infiltration. The immune effects of PO are associated with myeloid cell activation, and little is known about the action of PO on lymphocyte lineages, such as natural killer (NK) and T cells. We reveal that PO increases T-cell proliferation in vitro without negative effects on any activation marker. PO does not affect dendritic cell (DC) viability and increases the expansion of immature DC (iDC) and mature DC (mDC) at 100 μg/ml, and it stimulates expression of several DC co-stimulatory molecules, inducing the proliferation of allogeneic T cells. In contrast, PO decreases DC viability when added at day 5 post-expansion. PO is not toxic for NK cells at doses up to 100 μM and does not affect their activation, maturation, and cytotoxicity but tends to increase degranulation. This could be beneficial against target cells that show low sensitivity to NK cells, e.g., solid tumor cells. Finally, we have found great variability in PO response between donors. In summary, our in vitro results show that PO increases the number of costimulatory molecules on DC that prime T cells, favoring the production of effector T cells. This may support the future clinical development of PO in cancer treatment.

Azoximer bromide (AZB) was identified as an immunomodulator, and was initially developed and currently successfully indicated as one of several natural polyelectrolytes, a vaccine adjuvant, and an effective agent for the treatment of infectious and inflammatory diseases of viral, bacterial, and fungal origin. AZB has the potential to increase an individual’s resistance to local and general infection and is indicated for the treatment of viral infections, and has also demonstrated clinical efficacy in the treatment of a variety of secondary immunodeficiencies. However, AZB may offer long-term promise beyond use against infection. Multiple clinical trials and research studies in cancer patients have reported favourable outcomes with AZB as well as an optimal safety and tolerability profile. The findings raise the possibility of direct antitumor properties. This literature review analyses the novel mechanisms that mediate the AZB direct anticancer effects. Overall, the evidence suggests that AZB has the hallmark of an agent that could be used to support existing cancer treatments at different stages of disease.

Резюме. В работе приведены литературные данные и результаты собственных исследований, посвященных вирусу саркомы Капоши (KSHV) и его ассоциации с саркомой Капоши (СК), первичной выпотной лимфомой (ПВЛ) и мультицентрической болезнью Кастлемана (МБК). Полученные данные свидетельствуют о том, что все 3 основные клинические формы СК, диагностируемые в России, в высокой степени ассоциированы с KSHV, хотя и не в 100% случаев. Среди больных другими формами опухоли и не онкологических больных выявлены отдельные группы лиц с высоким уровнем инфицированности вирусом, что является фактором риска для возникновения СК. Обнаружено, что простата, особенно у больных карциномой простаты и СК, может быть серьезным источником вируса и интимные контакты с этими больными должны быть ограничены. Молекулярные варианты изолятов KSHV, циркулирующие в стране, относятся к двум основным генетическим подгруппам (А и С), широко представленным в Европейских странах и США, что указывает на общее происхождение вируса в этих странах. Приведены литературные данные о современных подходах в лечении.

Background. A new strategy of breast cancer management is required for effective disease prevention and control. Immunotherapy is one of promising options.Objective: to evaluate the effect of immunoadjuvant polyoxidonium on pathmorphological changes in breast tumors.Materials and methods. The study was performed in 75 patients with breast cancer: 50 patients received polyoxidonium in a neoadjuvant regimen (main group), 25 patients did not receive polyoxidonium (control group). Polyoxidonium at a dose of 12 mg was administered intramuscularly 1 time per day on the days 1, 2, 3, 5 and 7 before surgery; on the day 8, radical mastectomy was performed in patients of both groups, followed by histological examination and determination of the grade of therapeutic pathomorphosis of the tumor.Results. The proportion of cases with grade I therapeutic pathomorphosis was 58 %, grade II therapeutic pathomorphosis – 6 %. Pathomorphosis in metastatic lymph nodes was observed in 22.7 % of cases.Conclusion. The anti-tumor effect of polyoxidonium was confirmed on the basis of the induction of pathomorphosis of the tumor tissue of breast cancer.

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