Immunomodulation lab. Innate Immune Response Group.

Hospital Universitario La Paz

Cancer immunotherapy is one of the most attractive anticancer strategies nowadays. Most of these therapeutic approaches, such as transgenic CAR-T cells or Immune Checkpoint Inhibitors (ICI) intend to generate or activate T cell-mediated responses against cancer cells. However, harnessing innate immunity to lead stronger adaptive responses represents a powerful complementary approach. Along these lines, some stimuli such as fungal b-glucans and the tuberculosis vaccine BCG can induce long-lasting effects in monocytes, macrophages, or dendritic cells; when these pre-conditioned cells face a second stimulus, that can be unrelated to the first one, they generate boosted inflammatory responses. This phenomenon is known as trained immunity (TI) and is considered a memory process of innate immune cells, of potential application against cancer.

          TI inducers are currently administered experimentally through the intraperitoneal route or intradermically in the case of BCG. Although it is known that the BCG-mediated training is improved when administered through the mucosa, this use is limited due to its live-attenuated nature. Looking for alternatives, we have described that MV130, a mucosal immunotherapy composed of heat-killed (HK) bacteria, which has been tested in clinical trials with an excellent safety profile, induces TI when administered through the airways.

         Considering this state-of-the-art, in here we aim to propose MV130 or alternative formulations based on HK bacteria such as HKMtb as new  immunotherapies against cancer, either alone or in combination with current ICI-based treatments. We will study whether these immunotherapies impact on adaptive immune responses and the underlying mechanims. Mice will be vaccinated with this HKbacteria-based formulation, evaluating the induction of TI and their antitumoral capacity. Cell culture, ELISA  and flow cytometry are the main techniques to be applied. 

          In summary, this proposal aims to establish whether the generation of TI by heat-killed bacteria-based formulations represents a new immunotherapeutic avenue of potential clinical application against cancer.

Molecular Biomedicine
Carlos del Fresno Sánchez