Nanoparticulate Delivery of Cancer Cell Membrane Elicits Multiantigenic Antitumor Immunity

Ashley V. Kroll(University of California San Diego), Ronnie H. Fang(University of California San Diego), Yao Jiang(University of California San Diego), Jiarong Zhou(University of California San Diego), Xiaoli Wei(University of California San Diego), Chun Lai Yu(University of California San Diego), Jie Gao(University of California San Diego), Brian T. Luk(University of California San Diego), Diana Dehaini(University of California San Diego), Weiwei Gao(University of California San Diego), Liangfang Zhang(University of California San Diego)
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November 2, 2017
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Abstract

Anticancer vaccines train the body's own immune system to recognize and eliminate malignant cells based on differential antigen expression. While conceptually attractive, clinical efficacy is lacking given several key challenges stemming from the similarities between cancerous and healthy tissue. Ideally, an effective vaccine formulation would deliver multiple tumor antigens in a fashion that potently stimulates endogenous immune responses against those antigens. Here, it is reported on the fabrication of a biomimetic, nanoparticulate anticancer vaccine that is capable of delivering autologously derived tumor antigen material together with a highly immunostimulatory adjuvant. The two major components, tumor antigens and adjuvant, are presented concurrently in a fashion that maximizes their ability to promote effective antigen presentation and activation of downstream immune processes. Ultimately, it is demonstrated that the formulation can elicit potent antitumor immune responses in vivo. When combined with additional immunotherapies such as checkpoint blockades, the nanovaccine demonstrates substantial therapeutic effect. Overall, the work represents the rational application of nanotechnology for immunoengineering and can provide a blueprint for the future development of personalized, autologous anticancer vaccines with broad applicability.


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