Abstract 7: Gross thymic extract inhibits tumor growth by modulating the immune response in mice bearing Ehrlich ascites carcinoma cells

Abstract

Abstract Purpose. Gross thymic extract (GTE) obtained from pathogen-free pigs, a product also known as Thymax has previously been shown to boost various parameters of the immune system in aged mice, as well as activating human dentritic cells and the DC-directed T-cell response in vitro. The current study examines the immunomodulatory and chemopreventive effects of GTE in mice inoculated with Ehrlich ascites carcinoma (EAC) cells. Materials and Methods. Female Swiss albino mice were inoculated with EAC cells in the thigh to develop solid tumor. Oral treatment with GTE (5.45mg/kg body weight) was started either 14 days prior to tumor cell inoculation or 9 days post inoculation for mice bearing palpable tumors. Body weight and tumor growth were monitored until day 30 post-inoculation. The percentage of infiltrated CD4+, and CD8+T cells, natural killer (NK) cell activity and TNF-α expression in tumor cells were analyzed by flow cytometry and RT-PCR. Tumor histopathology was also examined, and blood lymphocytes and safety parameters were evaluated. GTE (Thymax) was kindly provided by YS Nature Company, Tokyo, Japan. Results. Treatment with GTE prior tumor cell inoculation showed tumor incidence in 61.1 % of the animals. Pre-treatment and post-treatment with GTE, markedly delayed tumor development and resulted in tumor weight reduction by -76.7% and -48.7% of untreated control, respectively. GTE, increased blood lymphocytes count by 60% and 53%, elevated the percentage of infiltrating CD4+ cells by144%, 94% and CD8+ T cells by 146%, 53%, for pre- and post-treatment, respectively. Oral intake of GTE, profoundly augmented NK cell cytolytic activity by 5.8 and 3.1 fold and TNF-α expression by 5.5 and 3.2 fold relative to the untreated control for pre-and post-treatment, respectively. Mice treated with GTE maintained normal body, spleen, liver and kidney weights and normal values for liver function enzymes including Aspartate aminotransferase (AST), Alanine aminotransferase (ALT) and Gamma-glutamyl transferase (GGT). Histopathological studies showed tumor tissue obtained from GTE -treated groups had a marked decrease in tumor cell density with increased vacuolation of their cytoplasm, marked increase of apoptotic cells and expansion of the degenerative areas. Conclusion: GTE is a safe, non-toxic agent, that exhibits a chemopreventive effect in mice bearing solid Ehrlich carcinoma via its ability to induce potent immunomodulation. This may suggest that GTE could be used for the treatment of solid tumors in humans. Citation Format: Azza I. Othman, Nariman K. Badr El-Din, Maggie E. Amer, Mamdooh Ghoneum. Gross thymic extract inhibits tumor growth by modulating the immune response in mice bearing Ehrlich ascites carcinoma cells [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 7.