Post-operative unadjuvanted therapeutic xenovaccination with chicken whole embryo vaccine suppresses distant micrometastases and prolongs survival in a murine Lewis lung carcinoma model

术后无佐剂治疗性异种接种鸡全胚胎疫苗可抑制小鼠 Lewis 肺癌模型中的远处微转移并延长生存期

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作者:Jan Aleksander Kraśko, Karolina Žilionytė, Adas Darinskas, Neringa Dobrovolskienė, Agata Mlynska, Svetlana Riabceva, Iosif Zalutsky, Marina Derevyanko, Vladimir Kulchitsky, Olga Karaman, Natalia Fedosova, Tatiana Vasyliyvna Symchych, Gennady Didenko, Vasyl Chekhun, Marius Strioga, Vita Pašukonienė

Abstract

Immunotherapy in the form of anticancer vaccination relies on the mobilization of the patient's immune system against specific cancer antigens. Instead of focusing on an autologous cell lysate, which is not always available in clinical practice, the present study investigates vaccines utilizing xenogeneic foetal tissue that are rich in oncofoetal antigens. Lewis lung carcinoma (LLC)-challenged C57BL/6 mice were treated with either a xenogeneic vaccine made from chicken whole embryo, or a xenogeneic vaccine made from rat embryonic brain tissue, supplemented with a Bacillus subtilis protein fraction as an adjuvant. Median and overall survival, size of metastatic foci in lung tissue and levels of circulating CD8a+ T cells were evaluated and compared with untreated control mice. Following primary tumour removal, a course of three subcutaneous vaccinations with xenogeneic chicken embryo vaccine led to significant increase in overall survival rate (100% after 70 days of follow-up vs. 40% in untreated control mice), significant increase in circulating CD8a+ T cells (18.18 vs. 12.6% in untreated control mice), and a significant decrease in the area and incidence of metastasis foci. The xenogeneic rat brain tissue-based vaccine did not improve any of the investigated parameters, despite promising reports in other models. We hypothesize that the proper selection of antigen source (tissue) can constitute an effective immunotherapeutic product.

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