PROVASCULAR THERAPY

Hypoxia is a well-recognized mechanism of resistance to radiotherapy. Chaotic tumoral neo-vasculature and impaired intermittent flow, combined with high tumor cell metabolism contribute to a poor oxygen supply to deep tumoral tissues. The efficacy of radiotherapy critically depends on local oxygen availability as full radiosensitivity dramatically decreases at pO2 below 10 mmHg. Restoring tumor perfusion and oxygenation has therefore been proposed to improve the outcome of radiotherapy, which include provascular therapies and vascular normalizing agents.
   
Therefore, since UTMD can activate the NO pathway and since the NO pathway is active in tumors, we hypothesize that UTMD can be used to improve local tumoral perfusion by NO mediated vasodilation for provascular radiosensitization for cancer therapy.

IMMUNOTHERAPY


Immunotherapy is emerging as a new modality for anti-cancer therapy. It is now successfully complementing radiotherapy, surgery and chemotherapy in our arsenal against cancer. Anti check point inhibitor therapies have created much enthusiasm for immunotherapy as they have shown response rates in ~30% of patients in many cancer types. Immunotherapy relies on restoring and/or triggering immune responses against cancer cells. The successes of check point inhibitors therapy, which releases the break on T cells have been shown to be directly related with the infiltration of CD4 and CD8 T cells and the reduction of T regulatory cells (Tregs) in the tumoral microenvironment in responders.  

We hypothesize that UTMD can modify the microenvironment towards an immunogenic phenotype by enhancing antibody and immune cell infiltration (increased vascular permeability), and thus improve immunotherapy of cancer.