Theranostics 2021; 11(14):6936-6949. doi:10.7150/thno.58173

Research Paper

A spontaneous multifunctional hydrogel vaccine amplifies the innate immune response to launch a powerful antitumor adaptive immune response

Xiuqi Liang*, Lu Li*, Xinchao Li*, Tao He, Songlin Gong, Shunyao Zhu, Miaomiao Zhang, Qinjie Wu, Changyang Gong

State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, 610041, P. R. China.
*These authors contributed equally to this work.

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Citation:
Liang X, Li L, Li X, He T, Gong S, Zhu S, Zhang M, Wu Q, Gong C. A spontaneous multifunctional hydrogel vaccine amplifies the innate immune response to launch a powerful antitumor adaptive immune response. Theranostics 2021; 11(14):6936-6949. doi:10.7150/thno.58173. Available from https://www.thno.org/v11p6936.htm

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Abstract

Substantial progress has been made with cancer immunotherapeutic strategies in recent years, most of which mainly rely on enhancing the T cell response. However, sufficient tumor antigen information often cannot be presented to T cells, resulting in a failed effector T cell response. The innate immune system can effectively recognize tumor antigens and then initiate an adaptive immune response. Here, we developed a spontaneous multifunctional hydrogel (NOCC-CpG/OX-M, Ncom Gel) vaccine to amplify the innate immune response and harness innate immunity to launch and maintain a powerful adaptive immune response.

Methods: Ncom Gel was formed by a Schiff base reaction between CpG-modified carboxymethyl chitosan (NOCC-CpG) and partially oxidized mannan (OX-M). The effects of the Ncom Gel vaccine on DCs and macrophages in vitro and antigen-specific humoral immunity and cellular immunity in vivo were studied. Furthermore, the antitumor immune response of the Ncom Gel vaccine and its effect on the tumor microenvironment were evaluated.

Results: The Ncom Gel vaccine enhanced antigen presentation to T cells by facilitating DC uptake and maturation and inducing macrophages to a proinflammatory subtype, further leading to a T cell-mediated adaptive immune response. Moreover, the innate immune response could be amplified via the promotion of antigen-specific antibody production. The Ncom Gel vaccine reversed the tumor immune microenvironment to an inflamed phenotype and showed a significant antitumor response in a melanoma model.

Conclusions: Our research implies the potential application of injectable hydrogels as a platform for tumor immunotherapy. The strategy also opens up a new avenue for multilayered cancer immunotherapy.

Keywords: spontaneous multifunctional hydrogel, Ncom Gel vaccine, cancer immunotherapy, innate immunity, adaptive immune response