Nanovaccine Incorporated with Hydroxychloroquine Enhances Antigen Cross-presentation and Promotes anti-Tumor Immune Responses.

Nanovaccine Incorporated with Hydroxychloroquine Enhances Antigen Cross-presentation and Promotes anti-Tumor Immune Responses.

ACS Appl Mater Interfaces. 2018 Aug 23;:

Authors: Liu J, Liu X, Han Y, Zhang J, Liu D, Ma G, Li C, Liu L, Kong D

Abstract
Induction of effective antigen-specific CD8+ T-cell responses is critical for cancer immunotherapy success. Hydroxychloroquine (HCQ) is a widely used classical antimalarial and antirheumatic drug. HCQ is also an endosomal membrane disrupting agent that can lead to vesicular swelling and membrane permeabilization, which likely facilitates the release of therapeutic agents from lysosomes into the cytoplasm. Here, we develop a minimalistic nanovaccine, which is comprised of poly (lactide-co-glycolide) acid (PLGA) nanoparticles encapsulating a physical mixture of ovalbumin (OVA, a model antigen) and HCQ (HCQ-OVA-PLGA NPs). We tested whether HCQ could spatiotemporally control the cytosolic delivery of antigens, enhance antigen processing and presentation via the MHC-I pathway, and thus generate a sufficient anti-tumor cytotoxic T-cell response. The results of in vitro experiments showed that HCQ-OVA-PLGA NPs significantly enhanced OVA escape from lysosomes into the cytoplasm within bone marrow-derived dendritic cells (BMDCs). We also observed that HCQ-OVA-PLGA NPs enhanced the expression level of MHC-I on dendritic cells (DCs) and improved cross-presentation of antigen, compared to Free OVA or OVA-PLGA NPs. Results of in vivo experiments confirmed that HCQ initiated Th1-type responses and strong CD8+ T-cell responses that induced tumor cell apoptosis. Moreover, vaccination of mice with HCQ-OVA-PLGA NPs effectively generated memory immune responses in vivo and prevented tumor progression. We conclude that co-encapsulation of HCQ with antigens in nanovaccines can boost antigen-specific antitumor immune responses, particularly through CD8+ T-cells, serving as a simple and effective platform for the treatment of tumors and infectious diseases.

PMID: 30136844 [PubMed - as supplied by publisher]

https://ift.tt/2MMxXVm