Immunogenic Cell Death Amplified by Co-localized Adjuvant Delivery for Cancer Immunotherapy

TitleImmunogenic Cell Death Amplified by Co-localized Adjuvant Delivery for Cancer Immunotherapy
Publication TypeJournal Article
Year of Publication2017
AuthorsFan, Y, Kuai, R, Xup, Y, Ochyl, LJ, Irvine, DJ, Moon, JJ
JournalNano Letters
Volume17
Issue12
Pagination7387 - 7393
Date Published2017/12//
ISBN Number1530-6984
Keywordscancer immunotherapy, cancer vaccine, Cell engineering immunogenic cell death, immunity, innate, microparticles, nanoparticle, Nanoparticles, responses, vaccines
Abstract

Despite their potential, conventional whole-cell cancer vaccines prepared by freeze thawing or irradiation have shown limited therapeutic efficacy in clinical trials. Recent studies have indicated that cancer cells treated with certain chemotherapeutics, such as mitoxantrone, can undergo immunogenic cell death (ICD) and initiate antitumor immune responses. However, it remains unclear how to exploit ICD for cancer immunotherapy. Here, we present a new material-based strategy for converting immunogenically dying tumor cells into a powerful platform for cancer vaccination and demonstrate their therapeutic potential in murine models of melanoma and colon carcinoma. We have generated immunogenically dying tumor cells surface-modified with adjuvant-loaded nanoparticles. Dying tumor cells laden with adjuvant nanodepots efficiently promote activation and antigen cross-presentation by dendritic cells in vitro and elicit robust antigen-specific CD8ce T-cells in vivo. Furthermore, whole tumor-cell vaccination combined with immune checkpoint blockade leads to complete tumor regression in similar to 78% of CT26 tumor-bearing mice and establishes long-term immunity against tumor recurrence. Our strategy presented here may open new doors to "personalised" cancer immunotherapy tailored to individual patient's tumor cells.

Short TitleNano Lett.