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Updated: Oct 5, 2025
Experimental Melanoma Immunotherapy Model Using Tumor Vaccination with a Hematopoietic Cytokine
Published on: February 24, 2023
Local therapy with an engineered oncolytic adenovirus enables antitumor response in non-injected melanoma tumors in
Dafne C A Quixabeira1, Victor Cervera-Carrascon1,2, Joao M Santos1,2
1Cancer Gene Therapy Group, Translational Immunology Research Program, University of Helsinki, Helsinki, Finland.
Abstract:
Intratumoral immunotherapies are entering clinical use but concerns remain regarding their effects on non-injected tumors. Here, we studied the impact of local treatment with an adenovirus coding for TNFa and IL-2 on systemic antitumor response in animals receiving aPD-1 (anti-programmed cell death protein 1) therapy. Using bilateral murine melanoma models, we tested systemic tumor response to combined therapy with anti-PD-1 and an adenovirus coding for TNFa and IL-2 ("virus"). Virus was given intratumorally (to one of the two tumors only) and aPD-1 monoclonal antibody systemically. We evaluated both tumors' response to treatment, overall survival, metastasis development, and immunological mechanisms involved with response. Consistent tumor control was observed in both injected and non-injected tumors, including complete response in all treated animals receiving aPD-1+ virus therapy. Mechanistically, virus injections enabled potent effector lymphocyte response locally, with systemic effects in non-injected tumors facilitated by aPD-1 treatment. Moreover, adenovirus therapy demonstrated immunological memory formation. Virus therapy was effective in preventing metastasis development. Local treatment with TNFa and IL-2 coding adenovirus enhanced systemic response to aPD-1 therapy, by re-shaping the microenvironment of both injected and non-injected tumors. Therefore, our pre-clinical data support the rationale for a trial utilizing a combination of aPD-1 plus virus for the treatment of human cancer.
Insights
Local immunotherapy using an adenovirus (coding for tumor necrosis factor alpha and interleukin-2) combined with systemic anti-programmed cell death protein 1 therapy eradicated tumors and prevented metastasis in preclinical models.
Area of Science:
- Immunology
- Oncology
- Gene Therapy
Background:
- Intratumoral immunotherapies show promise but their systemic effects on non-injected tumors require investigation.
- Combination strategies are crucial for enhancing antitumor responses and overcoming treatment resistance.
Purpose of the Study:
- To evaluate the systemic antitumor effects of combining intratumoral adenovirus-mediated gene therapy (encoding TNFa and IL-2) with systemic anti-programmed cell death protein 1 (aPD-1) therapy.
- To investigate the impact on both injected and non-injected tumors, survival, metastasis, and underlying immunological mechanisms.
Main Methods:
- Utilized bilateral murine melanoma models to assess the combined efficacy of intratumoral virus and systemic aPD-1.
- Monitored tumor response, overall survival, metastasis development, and analyzed immunological responses.
- Administered adenovirus intratumorally to one tumor and aPD-1 systemically.
Main Results:
- Consistent tumor control was observed in both injected and non-injected tumors.
- All animals receiving the combination therapy achieved complete tumor response.
- The combination therapy prevented metastasis and induced immunological memory.
Conclusions:
- Intratumoral adenovirus therapy enhances systemic antitumor response to aPD-1 therapy by modulating the tumor microenvironment.
- Preclinical data support the clinical investigation of combining aPD-1 with adenovirus-mediated gene therapy for cancer treatment.
- This combination strategy demonstrates significant potential for improving patient outcomes.
