Here is a comment on the research article:
This study developed an adenovirus-based vaccine co-encoding the renal cancer antigens CAIX and immune checkpoint PD-L1, and evaluated its therapeutic effects in mouse models of renal carcinoma. The main findings were:
- Ad-CAIX/Ad-PD-L1 vaccination significantly inhibited tumor growth in subcutaneous, lung metastasis and orthotopic models compared to Ad-CAIX alone.
- The vaccine promoted the induction and maturation of dendritic cells, and enhanced antigen-specific CD8+ T cell immune responses characterized by increased proliferation, cytokine production and multifunctionality.
- Depletion of CD8+ T cells abrogated the anti-tumor effect, indicating it relies on functional CD8+ T cell immunity.
- Mechanistically, the vaccine upregulated the infiltration of CD8+ T cells and cytokine production within tumors.
The strengths are exploring a combination vaccine strategy in multiple clinically relevant models, and characterizing the induced immune responses. Limitations include the use of mouse models and human antigen, and lack of testing in humanized mice or clinical trials.
Overall, this study provides a preclinical proof-of-concept that co-delivering PD-L1 and a tumor antigen via adenovirus induces potent anti-tumor CD8+ T cell immunity. The combination strategy warrants further investigation for its potential to improve cancer immunotherapy. Clarifying the antigenicity and induced epitopes could also help optimize vaccine design.
This study developed an adenovirus-based vaccine co-encoding the renal cancer antigens CAIX and immune checkpoint PD-L1, and evaluated its therapeutic effects in mouse models of renal carcinoma. The main findings were:
- Ad-CAIX/Ad-PD-L1 vaccination significantly inhibited tumor growth in subcutaneous, lung metastasis and orthotopic models compared to Ad-CAIX alone.
- The vaccine promoted the induction and maturation of dendritic cells, and enhanced antigen-specific CD8+ T cell immune responses characterized by increased proliferation, cytokine production and multifunctionality.
- Depletion of CD8+ T cells abrogated the anti-tumor effect, indicating it relies on functional CD8+ T cell immunity.
- Mechanistically, the vaccine upregulated the infiltration of CD8+ T cells and cytokine production within tumors.
The strengths are exploring a combination vaccine strategy in multiple clinically relevant models, and characterizing the induced immune responses. Limitations include the use of mouse models and human antigen, and lack of testing in humanized mice or clinical trials.
Overall, this study provides a preclinical proof-of-concept that co-delivering PD-L1 and a tumor antigen via adenovirus induces potent anti-tumor CD8+ T cell immunity. The combination strategy warrants further investigation for its potential to improve cancer immunotherapy. Clarifying the antigenicity and induced epitopes could also help optimize vaccine design.