Development of viral vectors expressing immunomodulatory antibodies as a new strategy for cancer gene therapy

Project information

Cancer is one of the leading causes of death, so it is imperative to develop new effective therapies. Recently, immunotherapy based on the administration of immunomodulatory monoclonal antibodies (MAbs) has induced objective responses in patients with advanced tumors, but has not been free of adverse effects. An alternative to reduce this toxicity is the use of gene therapy vectors that express MAbs locally in a prolonged and regulable manner.

Therefore, the main objective of the project is the development of viral vectors expressing immunomodulatory MAbs (anti PD-L1 and anti-CTLA-4) alone or in combination with immunostimulatory cytokines (IL-12 or IL-15). These vectors will be tested in a preclinical model of colorectal cancer (CRC) that mimics the situation of a patient with unresectable CRC who has received chemotherapy. Immunological parameters will also be analyzed in patients with unresectable CRC to allow parallels to be drawn with the preclinical model as a basis for future clinical applications of this therapy.

A secondary objective of the project is to test these immunomodulatory therapies in sepsis models, since this disease, often associated with cancer, has very similar immunosuppression mechanisms. Also in this case, immunological parameters will be analyzed in patients with sepsis associated or not with CRC.

• Convocation: Health R&D Health Projects. AES 2014
• Reference: PI14/01442
• Duration: 3 years
• Start date: January 1, 2015
• End date: December 31, 2017
• Funder: Instituto de Salud Carlos III y cofinanciado por el Fondo Europeo de Desarrollo Regional (FEDER) “Una manera de hacer Europa"
• Grant: 128.865 €
• Nature of project: National