Research ArticleCancer

Bacterial cytoplasmic membranes synergistically enhance the antitumor activity of autologous cancer vaccines

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Science Translational Medicine  07 Jul 2021:
Vol. 13, Issue 601, eabc2816
DOI: 10.1126/scitranslmed.abc2816

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More effective personalized cancer vaccines

Cancer-targeting vaccines are a promising therapy for patients after tumor removal. However, tumor tissues may not be strongly immunogenic, limiting vaccine efficacy. Here, Chen and colleagues developed an individualized cancer vaccine by incorporating cell membranes from the bacteria Escherichia coli and autologous tumor cell membranes into nanoparticles that could be given after tumor resection. The authors showed that these hybrid membrane nanoparticles induced strong tumor-specific immune responses with improved survival and long-term protection against tumor rechallenge in mice. There was no evidence of immune system overstimulation from bacterial cell wall contamination. These findings support the further development of these postoperative individualized cancer vaccines.

Abstract

Cancer vaccines based on resected tumors from patients have gained great interest as an individualized cancer treatment strategy. However, eliciting a robust therapeutic effect with personalized vaccines remains a challenge because of the weak immunogenicity of autologous tumor antigens. Utilizing exogenous prokaryotic constituents that act as adjuvants to enhance immunogenicity is a promising strategy to overcome this limitation. However, nonspecific stimulation of the immune system may elicit an undesirable immunopathological state. To specifically trigger sufficient antitumor reactivity without notable adverse effects, we developed an antigen and adjuvant codelivery nanoparticle vaccine based on Escherichia coli cytoplasmic membranes (EMs) and tumor cell membranes (TMs) from resected autologous tumor tissue. Introduction of the EM into the hybrid membrane nanoparticle vaccines (HM-NPs) induced dendritic cell maturation, thus activating splenic T cells. HM-NPs showed efficacy in immunogenic CT26 colon and 4T1 breast tumor mouse models and also efficiently induced tumor regression in B16-F10 melanoma and EMT6 breast tumor mouse models. Furthermore, HM-NPs provoked a strong tumor-specific immune response, which not only extended postoperative animal survival but also conferred long-term protection (up to 3 months) against tumor rechallenge in a CT26 colon tumor mouse model. Specific depletion of different immune cell populations revealed that CD8+ T and NK cells were crucial to the vaccine-elicited tumor regression. Individualized autologous tumor antigen vaccines based on effective activation of the innate immune system by bacterial cytoplasmic membranes hold great potential for personalized treatment of postoperative patients with cancer.

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