AUTHOR=Nabi Rafiq , Musarrat Farhana , Menk P. Lima Jose Cesar , Langohr Ingeborg M. , Chouljenko Vladimir N. , Kousoulas Konstantin G. 

TITLE=The Oncolytic herpes simplex virus type-1 (HSV-1) vaccine strain VC2 causes intratumor infiltration of functionally active T cells and inhibition of tumor metastasis and pro-tumor genes VEGF and PDL1 expression in the 4T1/Balb/c mouse model of stage four breast cancer

JOURNAL=Frontiers in Molecular Biosciences

VOLUME=Volume 10 - 2023

YEAR=2023

URL=https://www.frontiersin.org/journals/molecular-biosciences/articles/10.3389/fmolb.2023.1199068

DOI=10.3389/fmolb.2023.1199068

ISSN=2296-889X

ABSTRACT=Oncolytic viruses (OVs) provide new modalities for cancer therapy alone or in combination with synergistic immunotherapies and chemotherapeutics. Engineered Herpes Simplex Virus Type-1 (HSV-1) has shown strong promise for treating various cancers in experimental animal models and in human patients, with some virus strains licensed to treat human melanoma and gliomas. Herein, we have utilized the mutant HSV-1 (VC2) to treat stage four 4T1 breast cancer in the syngeneic and immunocompetent BALB/cJ mouse model that exhibits efficient metastasis to the lung and other organs. VC2 replicated efficiently in 4T1 cells and cell culture, achieving titers similar to those in African monkey kidney (Vero) cells. Intra-tumor treatment with VC2 did not appreciably reduce average primary tumor sizes, but a significant reduction of lung metastasis was noted in mice treated intratumorally with VC2 but not with ultraviolet-inactivated VC2. This reduction of metastasis was associated with increased T cell infiltration comprised of CD4+ and CD4+CD8+ double-positive T cells. Characterization of purified tumor-infiltrating T cells revealed a significant improvement in their proliferation ability compared to controls. In addition, significant T-cell infiltration was observed in the metastatic nodules associated with reducing pro-tumor PD-L1 and VEGF gene transcription. These results show that VC2 therapy can improve anti-tumor response related to better control of tumor metastasis. Improve T cell responses and reduce pro-tumor biomarker gene transcription. VC2 holds promise for further development as an oncolytic and immunotherapeutic approach to treating breast and other cancers.