Navoximod modulates local HSV-1 replication to reshape tumor immune microenvironment for enhanced immunotherapy via an injectable hydrogel

by Selleckchem | Nov 03 2023

Oncolytic virotherapy can lead to tumor lysis and systemic anti-tumor immunity, but the therapeutic potential in humans is limited due to the impaired virus replication and the insufficient ability to overcome the immunosuppressive tumor microenvironment (TME). To solve the above problems, we identified that Indoleamine 2, 3-dioxygenase 1 (IDO1) inhibitor Navoximod promoted herpes simplex virus type 1 (HSV-1) replication and HSV-1-mediated oncolysis in tumor cells, making it a promising combination modality with HSV-1-based virotherapy. Thus, we loaded HSV-1 and Navoximod together in an injectable and biocompatible hydrogel (V-Navo@gel) for hepatocellular carcinoma (HCC) virotherapy. The hydrogel formed a local delivery reservoir to maximize the viral replication and distribution at the tumor site with a single-dose injection. Notably, V-Navo@gel improved the disease-free survival time of HCC- bearing mice and protects the mice against tumor recurrence. What's more, V-Navo@gel also showed an effective therapeutic efficacy in the rabbit orthotopic liver cancer model. Mechanistically, we further discovered that our combination strategy entirely reprogramed the TME through single-cell RNA sequencing. All these results collectively indicated that the combination of Navoximod with HSV-1 could boost the viral replication and reshape TME for tumor eradication through the hydrogel reservoir.

Comments:

That sounds like an exciting development in oncolytic virotherapy research! The use of oncolytic viruses for tumor treatment has shown promise, but there are challenges associated with limited virus replication and the immunosuppressive tumor microenvironment (TME). However, your study has identified an interesting solution by combining an Indoleamine 2, 3-dioxygenase 1 (IDO1) inhibitor called Navoximod with herpes simplex virus type 1 (HSV-1) in an injectable hydrogel called V-Navo@gel for hepatocellular carcinoma (HCC) virotherapy.

By incorporating Navoximod with HSV-1 in the hydrogel, you created a local delivery reservoir that maximizes viral replication and distribution specifically at the tumor site. This approach has led to improved disease-free survival time in HCC-bearing mice and protection against tumor recurrence. The efficacy of V-Navo@gel was also demonstrated in a rabbit orthotopic liver cancer model, further supporting its therapeutic potential.

Additionally, your research revealed that this combination strategy has the ability to reprogram the tumor microenvironment through single-cell RNA sequencing. This finding suggests that the combination of Navoximod with HSV-1 can not only enhance viral replication but also reshape the TME, potentially leading to more effective tumor eradication.

Overall, your study presents an innovative approach to addressing the limitations of oncolytic virotherapy in humans. The combination of Navoximod and HSV-1 within the V-Navo@gel hydrogel holds promise for improving virotherapy outcomes and warrants further investigation and development.