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Hyaluronic acid-antigens conjugates trigger potent immune response in both prophylactic and therapeutic immunization in a melanoma model

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Abstract

Immunotherapy of advanced melanoma has encountered significant hurdles in terms of clinical efficacy. Here, we designed a clinically translatable hyaluronic acid (HA)-based vaccine delivering a combination of major histocompatibility complex (MHC) class I- and class II-restricted melanoma antigens (TRP2 and Gp100, respectively) conjugated to HA. HA-nanovaccine (HA-TRP2-Gp100 conjugate) exhibited tropism in the lymph nodes and promoted stimulation of the immune response (2.3-fold higher than the HA+TRP2+Gp100). HA-nanovaccine significantly delayed the growth of B16F10 melanoma and extended survival in both the prophylactic and therapeutic settings (median survival of 22 and 27, respectively, vs 17 days of the untreated group). Moreover, mice prophylactically treated with the HA-nanovaccine displayed significantly higher CD8+ and CD4+ T-cell/Treg ratios in both the spleen and tumor at day 16, suggesting that the HA-nanovaccine overcame the immunosuppressive tumor microenvironment. Superior infiltration of active CD4+ and CD8+ T cells was observed at the endpoint. This study supports the conclusion that HA potentiates the effect of a combination of MHC I and MHC II antigens via a potent immune response against melanoma.

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The data generated during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

We thank Nicolas Dauguet for the support of flow cytometry analysis. We also thank Valentina Marotti for her help in design figures with biorender.com.

Funding

A.M. is supported by the Marie Skłodowska-Curie Actions for an Individual European Fellowship under the European Union’s Horizon 2020 research and innovation program (grant agreement no. 887609) and by an FRS-FNRS fellowship (grant agreement no. 40000747) (Belgium). M.B. is supported by a Televie grant. V.P. is supported by Fonds de la Recherche Scientifique—Fonds National de la Recherche Scientifique (FRS-FNRS, grant agreement nos. 33669945, 40003419).

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  1. Advanced Drug Delivery and Biomaterials, UCLouvain, Louvain Drug Research Institute, Avenue Mounier 73 B1.73.12, 1200, Brussels, Belgium

    Alessio Malfanti, Mathilde Bausart, Kevin Vanvarenberg, Bernard Ucakar & Véronique Préat

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  1. Alessio Malfanti
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Contributions

A.M. and V.P. designed the research plan and the experiments, conceived the project, and obtained financial support. A.M. M.B. K.V. and B.U. performed the experiments. A.M. analyzed the data. A.M. and V.P. wrote the paper with revisions from all authors.

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Correspondence to Alessio Malfanti or Véronique Préat.

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The animal experiments were conducted as per the guidelines of the Belgian national regulation guidelines, in agreement with EU Directive 1010/63/EU concerning the use of animals for experimental purposes. The study protocols were approved by the ethical committee for animal care of the health science sector of the Université Catholique de Louvain (2019/UCL/MD/004, 2021/UCL/MD/052).

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Malfanti, A., Bausart, M., Vanvarenberg, K. et al. Hyaluronic acid-antigens conjugates trigger potent immune response in both prophylactic and therapeutic immunization in a melanoma model. Drug Deliv. and Transl. Res. 13, 2550–2567 (2023). https://doi.org/10.1007/s13346-023-01337-4

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