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Tumor Immunotherapy01:27

Tumor Immunotherapy

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Immunotherapy is a treatment that boosts or manipulates the immune system to fight diseases, including cancer. For instance, by stimulating an immune response through vaccinations against viruses that cause cancers, like hepatitis B virus and human papillomavirus, these diseases can be prevented. Nonetheless, some cancer cells can avoid the immune system due to their rapid mutation and division. The immune response to many cancers involves three phases: elimination, equilibrium, and escape.
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The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
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Cancer Vaccines01:30

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Updated: Mar 27, 2026

Paramyxoviruses for Tumor-targeted Immunomodulation: Design and Evaluation Ex Vivo
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Radiotherapy synergizes with an inducible AAV-based immunotherapy platform to program local and systemic antitumor

Sonia Marco1, Myriam Fernández1, Beatriz Honorato1

  • 1Solid Tumors Program, Cima-Cancer Center Clínica Universidad de Navarra (CCUN), Pamplona, Spain.

Cancer Cell
|March 24, 2026
PubMed
Summary

Radiotherapy combined with adeno-associated virus (AAV) gene therapy enhances the immune system to fight cancer. This approach creates an immunostimulatory tumor microenvironment, leading to effective antitumor responses.

Keywords:
AAVIL-12cancer gene therapyepigenetic regulationimmunotherapyradiotherapysystemic immunitytumor microenvironment

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Area of Science:

  • Oncology
  • Immunotherapy
  • Gene Therapy

Background:

  • Radiotherapy (RT) can stimulate anti-cancer immunity but is often limited by immunosuppressive factors.
  • Adeno-associated vectors (AAVs) show enhanced tumor transduction after RT due to epigenetic modifications.
  • Developing strategies to overcome RT-induced immunosuppression is crucial for effective cancer treatment.

Purpose of the Study:

  • To design an AAV-based platform for localized delivery of immunostimulatory cytokines into irradiated tumors.
  • To investigate the efficacy of combining RT with an interferon (IFN)-inducible AAV vector encoding for IL-12 (AAV-iIL12).
  • To evaluate the safety and antitumor responses generated by this combined approach.

Main Methods:

  • Development of an AAV vector with an IFN-inducible promoter for spatial control of transgene expression.
  • Local delivery of AAV-iIL12 into irradiated tumors.
  • Assessment of cytokine production, tumor microenvironment (TME) modulation, and antitumor responses (local and systemic).
  • Evaluation of IFNγ and FAS dependency in antitumor mechanisms.

Main Results:

  • AAV-iIL12 achieved efficient local IL-12 production without significant toxicity compared to constitutive systems.
  • The combination of RT and AAV-iIL12 created a highly immunostimulatory TME.
  • Robust local and systemic antitumor responses were observed, dependent on IFNγ and FAS.
  • This approach effectively overcame common immune-evasion mechanisms.

Conclusions:

  • Radiation coupled with AAV-based immune-gene delivery is an efficient strategy to enhance antitumor immunity.
  • This approach offers a safe and effective method for cancer treatment by modulating the TME.
  • The localized and inducible cytokine delivery overcomes limitations of conventional immunotherapy.