复制缺陷型黏液瘤病毒诱导促炎反应作为卵巢癌的单一疗法及化疗和 DC 免疫疗法的佐剂

Myxoma virus (MYXV), a rabbit-specific poxvirus and non-pathogenic in humans and mice, is an excellent candidate oncolytic virus for cancer therapy. MYXV also has immunotherapeutic benefits. In ovarian cancer (OC), immunosuppressive tumor-associated macrophages (TAMs) are key to inhibiting antitumor immunity while hindering therapeutic benefit by chemotherapy and dendritic cell (DC) vaccine. Because MYXV favors binding/entry of macrophages/monocytes, we examined the therapeutic potential of MYXV against TAMs.

We found previously that a replication-defective MYXV with targeted deletion of an essential gene, M062R , designated Δ M062R MYXV, activated both the host DNA sensing pathway and the SAMD9 pathway. Treatment with Δ M062R confers therapeutic benefit comparable to that of wild-type replicating MYXV in preclinical models.

Here we found that Δ M062R MYXV, when integrated with cisplatin and DC immunotherapy, further improved treatment benefit, likely through promoting tumor antigen-specific T cell function.

Moreover, we also tested Δ M062R MYXV in targeting human immunosuppressive TAMs from OC patient ascites in a co-culture system.

We found that Δ M062R treatment subverted the immunosuppressive properties of TAMs and elevated the avidity of cytokine production in tumor antigen-specific CD4 + T cells.

Overall, Δ M062R presents a promising immunotherapeutic platform as a beneficial adjuvant to chemotherapy and DC vaccine.