Use of parvovirus B19-like particles in self-illuminated photodynamic therapy for solid tumors.

Bioluminescence resonance energy transfer photodynamic therapy, which uses light generated by bioluminescent proteins to activate photosensitizers and produce reactive oxygen species without the need for external irradiation, has shown promising results in cancer models. However, the characterization of delivery systems that can incorporate the components of this therapy for preferential delivery to the tumor remains necessary. In this work, we have characterized parvovirus B19-like particles (B19V-VLPs) as a platform for a photosensitizer and a bioluminescent protein. By chemical and biorthogonal conjugation, we conjugated rose Bengal photosensitizer and firefly luciferase to B19V-VLPs and a protein for added specificity. The results showed that B19V-VLPs can withstand decoration with all three components without affecting its structure or stability. The conjugated luciferase showed activity and was able to activate rose Bengal to produce singlet oxygen without the need for external light. The photodynamic reaction generated by the functionalized VLPs-B19 can decrease the viability of tumor cells in vitro and affect tumor growth and metastasis in the 4 T1 model. Treatment with functionalized VLPs-B19 also increased the percentage of CD4 and CD8 cell populations in the spleen and in inguinal lymph nodes compared to vehicle-treated mice. Our results support B19V-VLPs as a delivery platform for bioluminescent photodynamic therapy components to solid tumors.

Therapy with multi-epitope virus-like particles of B19 parvovirus reduce tumor growth and lung metastasis in an aggressive breast cancer mouse model.

Triple-negative breast cancer is a major health problem that lacks molecular targets for therapy. Neoepitopes represent a viable option to induce antitumor immune responses, but they have limitations, such as low immunogenicity and tolerance induction. Parvovirus B19 virus-like particles may be used to deliver neoepitopes to prime cellular immunity. We designed and evaluated the therapeutic effect of VP2 B19-virus-like particles, with multi-neoepitopes, in a 4T1 breast cancer model. Balb/c mice received four therapeutic immunizations with multi-neoepitopes-virus-like, wild type-virus-like, vehicle, or virus-like plus Cry1Ac adjuvant particles, intraperitoneally and peritumorally. Tumor growth, lung macro-metastasis, and specific immune responses were evaluated. Therapeutic administration of multi-epitopes virus-like particles significantly delayed tumor growth and decreased the lung macro-metastasis number, in comparison to treatment with wild type-virus-like particles, which surprisingly also elicited antitumoral effects that were improved with the adjuvant. Only treatments with multi-epitope virus-like particles induced specific proliferative responses of CD8 and CD4 T lymphocytes and Granzyme-B production in lymphatic nodes local to the tumor. Treatment with recombinant multiple neoepitopes-virus-like particles induced specific cellular responses, inhibited tumor growth and macro-metastasis, thus B19-virus-like particles may function as an effective delivery system for neoepitopes for personalized immunotherapy.