An Approach to Breast Cancer Immunotherapy: The Apoptotic Activity of Recombinant Anti-Interleukin-6 Monoclonal Antibodies in Intact Tumour Microenvironment of Breast Carcinoma.

Current work is one of our comprehensive preclinical studies, a new approach to breast cancer (BC) immunotherapy through induction of tumour cell apoptosis. Tumour growth is not just a result of uncontrolled cell proliferation but also of reduced apoptosis. High levels of interleukin-6 (IL-6) are associated with metastatic BC and correlated with poor survival as it promotes growth of tumour-initiating cells during early tumorigenesis protecting these cells from apoptosis. Therefore, this study aims at investigating the potential of anti-IL-6 monoclonal antibodies to suppress IL-6 proliferative/anti-apoptotic activities in intact tumour microenvironment of BC. Fresh sterile tumour and normal breast tissue specimens were taken from 50 female Egyptian patients with BC undergoing radical mastectomy. A unique tissue culture system designed to provide cells of each intact tumour/normal tissue sample with its proper microenvironment either supplemented or not with anti-IL-6 monoclonal antibodies. To evaluate the apoptotic activity of anti-IL-6 as a novel candidate for BC treatment strategy, we compared its effects with those obtained using tumour necrosis-related apoptosis-inducing ligand TRAIL as an established apoptotic agent. Our results revealed that levels of either anti-IL-6- or TRAIL-induced apoptosis in the tumour or normal tissue cultures were significantly higher than those in their corresponding untreated ones (P < 0.001). No statistically significant differences have been found between apoptosis levels induced by anti-IL-6 monoclonal antibodies and those induced by TRAIL. Recombinant anti-IL-6 monoclonal antibodies could represent a novel effective element of immunotherapeutic treatment strategy for BC. The selectivity and anti-apoptotic potential of anti-IL-6 is highly hopeful in IL-6- abundant BC tumour microenvironment.

Production of pro-inflammatory cytokines (GM-CSF, IL-8 and IL-6) by monocytes from fasciolosis patients.

The production of pro-inflammatory cytokines by monocytes in vitro has been measured in eight patients with acute fasciolosis and 15 patients in the chronic stage of the disease, before and after stimulation by excretory/secretory Fasciola antigen. Results were compared with those of a control group of 12 individuals. The monocytes from patients with acute fasciolosis produced significantly higher levels of GM-CSF, IL-8 and IL-6 as compared to controls. With chronicity, the production of these cytokines was decreased as compared to the acute stage probably due to decreased antigen level in blood. Stimulation of monocytes of healthy control with E/S Fasciola antigen was accompanied with a markedly increased production of pro-inflammatory cytokines, while monocytes from patients with acute or chronic fasciolosis revealed minimal increase in production. This denoted the importance of E/S Fasciola antigen as an activator of monocytes. A second exposure to the same antigen was accompanied with a limited response.