An oncolytic virus-T cell chimera for cancer immunotherapy

Area of Science:

• Oncology
• Immunotherapy
• Gene Therapy

Background:

• Oncolytic adenoviruses (OAs) show promise for cancer therapy but face challenges with tumor delivery and immune evasion.
• Tumor cells often express immune checkpoints like PD-L1, hindering anti-tumor immune responses.

Purpose of the Study:

• To develop a novel therapeutic strategy combining virotherapy and cell therapy for enhanced cancer treatment.
• To engineer OAs to target tumors more effectively and overcome immune suppression.

Main Methods:

• OAs were engineered to express a Cas9 system targeting the PDL1 gene.
• OAs were conjugated onto T cells using T cell-specific antigens for targeted delivery (ONCOTECH).
• ONCOTECH was evaluated in preclinical mouse models of melanoma, pancreatic adenocarcinoma, lung cancer, and glioblastoma.

Main Results:

• ONCOTECH demonstrated efficient accumulation of OAs within tumor cells following intravenous administration.
• PD-L1 expression in melanoma tumors was reduced by 50% after ONCOTECH treatment.
• A single administration of ONCOTECH resulted in 80% survival in the melanoma model over 70 days.

Conclusions:

• ONCOTECH represents a promising translational technology integrating virotherapy and cell therapy.
• This approach effectively enhances tumor delivery of OAs and modulates the tumor immune microenvironment.
• ONCOTECH shows significant potential for treating various solid tumors.