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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1355566
This article is part of the Research Topic Vector-based Cancer Immunotherapy View all 10 articles

Synergistic antitumor immune response mediated by paclitaxel-conjugated nanohybrid oncolytic adenovirus with dendritic cell therapy

Provisionally accepted
In-Wook Kim In-Wook Kim 1A-Rum Yoon A-Rum Yoon 1Jinwoo Hong Jinwoo Hong 2Dayananda Kasala Dayananda Kasala 1Chae-Ok Yun Chae-Ok Yun 1*
  • 1 Hanyang University, Seoul, Republic of Korea
  • 2 GeneMedicine Co., Ltd, Seoul, Republic of Korea

The final, formatted version of the article will be published soon.

    Dendritic cell (DC)-based vaccines have emerged as a promising strategy in cancer immunotherapy due to low toxicity. However, the therapeutic efficacy of DC as a monotherapy is insufficient due to highly immunosuppressive tumor environment. To address these limitations of DC as immunotherapeutic agent, we have developed a polymeric nanocomplex incorporating (1) oncolytic adenovirus (oAd) co-expressing interleukin (IL)-12 and granulocyte-macrophage colony-stimulating factor (GM-CSF) and ( 2) arginine-grafted bioreducible polymer with PEGylated paclitaxel (APP) to restore antitumor immune surveillance function in tumor milieu and potentiate immunostimulatory attributes of DC vaccine. Nanohybrid complex (oAd/APP) in combination with DC (oAd/APP+DC) induced superior expression level of antitumor cytokines (IL-12, GM-CSF, and interferon gamma) than either oAd/APP or DC monotherapy in tumor tissues, thus resulting in superior intratumoral infiltration of both endogenous and exogenous DCs. Furthermore, oAd/APP+DC treatment led superior migration of DC to secondary lymphoid organs, such as draining lymph nodes and spleen, in comparison with either monotherapy. Superior migration profile of DCs in oAd/APP+DC treatment group resulted in more prolific activation of tumor-specific T cells in these lymphoid organs and greater intratumoral infiltration of T cells. Additionally, oAd/APP+DC treatment led to lower subset of tumor infiltrating lymphocytes and splenocytes being immunosuppressive

    Keywords: DC, Oncolytic Ad, Nanohybrid, Therapeutic vaccine, anti-immune response, IFNgamma, T cells, Treg

    Received: 14 Dec 2023; Accepted: 06 May 2024.

    Copyright: © 2024 Kim, Yoon, Hong, Kasala and Yun. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Chae-Ok Yun, Hanyang University, Seoul, 133-791, Republic of Korea

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