Tumor vaccines based on oncolytic measles viruses

Tumor vaccines based on oncolytic measles viruses

The concept of therapeutic vaccination against cancer is based on the induction of robust and durable immune responses against tumor antigens that are selectively expressed in tumors. Whereas immune responses against foreign antigens can be induced relatively easily, the immune system is usually tolerant towards self-antigens.  A potent measure to break such immunological tolerance is the presentation of self-antigens in the context of inflammatory signals or strong foreign antigens.

Recombinant, attenuated measles viruses (aMV) are derived from live-attenuated vaccine strains protecting against measles with proven safety and efficacy in millions of individuals. aMV have excellent vaccine properties, probably offering lifelong protection. Besides its capacity as a live vaccine against measles, aMV are being broadly developed as a vaccine platform against diverse infectious diseases (e.g. dengue fever). aMV also have the natural feature to preferentially infect tumor cells and simultaneously are toxic for such infected cells. Therefore, safety and preliminary data regarding oncolytic efficiency of aMV are currently being tested in Phase I clinical trials in cancer patients.

Overall, it is reasonable to further develop aMV for oncolysis and simultaneous directed in vivo vaccination, and to use their combined tumor selectivity, cytotoxicity and high immunogenicity to fight cancer. In this context, the focus lies on optimizing genetic targeting towards tumor-specific antigens which is possible with aMV, and on improving anti-tumor activity by using new, highly-specific tumor antigens as targets for the induced immune response. The partner BioNTech RNA Pharmaceuticals has access to a collection of proprietary tumor-associated targets which are ideal for developing tumor vaccines, as well as to diverse mouse models for comparison of different antigen-specific immunization strategies and demonstration of anti-tumoral effects.

The aim of the project "Tumor vaccines based on oncolytic measles viruses" is the pre-clinical analysis of novel modified aMV which are effective against tumors: In addition to direct tumor lysis, these aMV are intended to elicit individual, patient-specific immune responses by over-expression of patient-specific tumor antigens. The intended outcome of this project is to preclinically validate prototypical aMV for simultaneous oncolysis (tumor cell destruction) and in vivo vaccination.

Keywords 

  • Immunotherapy
  • oncolytic viruses
  • entry targeting
  • tumor-specific antigens

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