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

Immunogenic Cell Death Amplified by Co-localized Adjuvant Delivery for Cancer Immunotherapy.
Author Information (click to view)

Fan Y, Kuai R, Xu Y, Ochyl LJ, Irvine DJ, Moon J,


Fan Y, Kuai R, Xu Y, Ochyl LJ, Irvine DJ, Moon J, (click to view)

Fan Y, Kuai R, Xu Y, Ochyl LJ, Irvine DJ, Moon J,

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Nano letters 2017 11 16() doi 10.1021/acs.nanolett.7b03218
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 shown that cancer cells treated with certain chemotherapeutics, such as mitoxantrone, can undergo immunogenic cell death (ICD) and initiate anti-tumor immune responses. However, it remains unclear how ICD can be exploited for cancer immunotherapy. Here, we present a new biomaterial-based strategy for converting immunogenically dying tumor cells into a powerful platform for cancer vaccination and demonstrate their immunogenicity in murine models of melanoma and colon carcinoma. We have generated immunogenically dying tumor cells surface-modified with adjuvant-loaded nano-depots. Dying tumor cells laden with nano-depots efficiently promote activation and antigen cross-presentation by dendritic cells and elicit robust levels of antigen-specific CD8+ T cells. Furthermore, whole tumor-cell vaccination combined with immune checkpoint blockade leads to complete tumor regression in ~78% of CT26 tumor-bearing mice and establishes long-term immunity against tumor recurrence. Our strategy presented here may open new doors to personalized cancer immunotherapy tailored to individual patient’s tumor cells.

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