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Updated: Jan 5, 2026
Paramyxoviruses for Tumor-targeted Immunomodulation: Design and Evaluation Ex Vivo
Published on: January 7, 2019
Repurposing rotavirus vaccines for intratumoral immunotherapy can overcome resistance to immune checkpoint blockade
Tala Shekarian1,2,3,4, Eva Sivado2,3,5, Anne-Catherine Jallas2,5
1Centre de Recherche en Cancérologie de Lyon (CRCL), UMR INSERM U1052 CNRS 5286 Université de Lyon, 69008 Lyon, France.
Abstract:
Although immune checkpoint-targeted therapies are currently revolutionizing cancer care, only a minority of patients develop durable objective responses to anti-PD-1, PD-L1, and CTLA-4 therapy. Therefore, new therapeutic interventions are needed to increase the immunogenicity of tumors and overcome the resistance to these immunotherapies. Oncolytic properties of common viruses can be exploited for the priming of antitumor immunity, and such oncolytic viruses are currently in active clinical development in combination with immune checkpoint-targeted therapies. However, the routine implementation of these therapies is limited by their manufacturing constraints, the risk of exposure of clinical staff, and the ongoing regulations on genetically modified organisms. We sought to determine whether anti-infectious disease vaccines could be used as a commercially available source of immunostimulatory agents for cancer immunotherapy. We found that rotavirus vaccines have both immunostimulatory and oncolytic properties. In vitro, they can directly kill cancer cells with features of immunogenic cell death. In vivo, intratumoral rotavirus therapy has antitumor effects that are dependent on the immune system. In several immunocompetent murine tumor models, intratumoral rotavirus overcomes resistance to and synergizes with immune checkpoint-targeted therapy. Heat- and UV-inactivated rotavirus lost their oncolytic activity but kept their synergy with immune checkpoint-targeted antibodies through the up-regulation of the double-stranded RNA receptor retinoic acid-induced gene 1 (RIG-I). Rotavirus vaccines are clinical-grade products used in pediatric and adult populations. Therefore, in situ immunization strategies with intratumoral-attenuated rotavirus could be implemented quickly in the clinic.
Insights
Rotavirus vaccines show promise as a novel cancer immunotherapy, demonstrating both direct tumor cell killing and synergistic effects with existing immune checkpoint therapies. This approach offers a readily available and potentially safer alternative to oncolytic viruses.
Area of Science:
- Oncology
- Immunology
- Virology
Background:
- Immune checkpoint inhibitors (anti-PD-1, PD-L1, CTLA-4) have transformed cancer care but benefit only a subset of patients.
- Novel strategies are needed to enhance tumor immunogenicity and overcome resistance to current immunotherapies.
- Oncolytic viruses are being explored for cancer immunotherapy but face manufacturing and regulatory hurdles.
Purpose of the Study:
- To investigate if existing anti-infectious disease vaccines can serve as immunostimulatory agents for cancer immunotherapy.
- To evaluate the potential of rotavirus vaccines as a novel cancer therapeutic.
Main Methods:
- In vitro assessment of rotavirus's direct effects on cancer cells, including immunogenic cell death.
- In vivo studies using intratumoral rotavirus administration in immunocompetent murine tumor models.
- Combination therapy studies with rotavirus and immune checkpoint inhibitors.
- Evaluation of inactivated rotavirus to understand the role of oncolysis versus immunostimulation.
Main Results:
- Rotavirus exhibits both immunostimulatory and direct oncolytic properties, inducing immunogenic cell death in cancer cells.
- Intratumoral rotavirus therapy demonstrated significant antitumor effects dependent on an intact immune system.
- Rotavirus synergized with and overcame resistance to immune checkpoint-targeted therapy in multiple tumor models.
- Inactivated rotavirus retained synergy with immune checkpoint antibodies, mediated by RIG-I pathway activation, despite losing oncolytic activity.
Conclusions:
- Rotavirus vaccines possess both immunostimulatory and oncolytic capabilities, making them a viable candidate for cancer immunotherapy.
- Intratumoral rotavirus therapy can enhance the efficacy of immune checkpoint inhibitors.
- Clinical-grade rotavirus vaccines offer a potentially rapid and accessible strategy for in situ cancer immunization.
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