Development and Optimal Immune Strategy of an Alum-Stabilized Pickering emulsion for Cancer Vaccines

Author:

Peng Sha123,Yan Yumeng14,Ngai To5ORCID,Li Jianjun146ORCID,Ogino Kenji23ORCID,Xia Yufei146

Affiliation:

1. State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, China

2. Graduate School of Bio-Applications and Systems Engineering, Tokyo University of Agriculture and Technology, 2-24-16 Nakacho, Tokyo 184-8588, Japan

3. Institute of Global Innovation Research, Tokyo University of Agriculture and Technology, 2-24-16 Nakacho, Tokyo 184-8588, Japan

4. University of Chinese Academy of Sciences, Beijing 100049, China

5. Department of Chemistry, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong, China

6. Innovation Academy for Green Manufacture, Chinese Academy of Sciences, Beijing 100190, China

Abstract

Therapeutic cancer vaccines are considered as one of the most cost-effective ways to eliminate cancer cells. Although many efforts have been invested into improving their therapeutic effect, transient maturation and activations of dendritic cells (DCs) cause weak responses and hamper the subsequent T cell responses. Here, we report on an alum-stabilized Pickering emulsion (APE) that can load a high number of antigens and continue to release them for extensive maturation and activations of antigen-presenting cells (APCs). After two vaccinations, APE/OVA induced both IFN-γ-secreting T cells (Th1) and IL-4-secreting T cells (Th2), generating effector CD8+ T cells against tumor growth. Additionally, although they boosted the cellular immune responses in the spleen, we found that multiple administrations of cancer vaccines (three or four times in 3-day intervals) may increase the immunosuppression with more PD-1+ CD8+ and LAG-3+ CD8+ T cells within the tumor environment, leading to the diminished overall anti-tumor efficacy. Combining this with anti-PD-1 antibodies evidently hindered the suppressive effect of multiple vaccine administrations, leading to the amplified tumor regression in B16-OVA-bearing mice.

Funder

National Key Research and Development Program of China

CAS Project for Young Scientists in Basic Research

“From 0 to 1” Original Innovation Project of Basic Frontier Scientific Research Program of Chinese Academy of Sciences

Beijing Nova Program

Foundation for Innovative Research Groups of the National Natural Science Foundation of China

Pilot Project of Chinese Academy of Sciences

Distinguished Young Scholars of the National Natural Science Foundation of China

Major Project of the National Natural Science Foundation of China

Youth Innovation Promotion Association of the Chinese Academy of Sciences

Foundation of Innovation Academy for Green Manufacture Institute, Chinese Academy of Sciences

Publisher

MDPI AG

Subject

Pharmacology (medical),Infectious Diseases,Drug Discovery,Pharmacology,Immunology

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