Post-doctoral Fellowship Grant Awarded to Marc Garcia Moure

Currently, the spotlight in treatment of cancer is on immunotherapy, an encouraging strategy that has brought hope to many patients. However, DIPGs are “cold” tumors, which means they are barely noticeable to the patient’s own immune system. Consequently, the lack of a basal anti-tumor immune response is being a major drawback for immunotherapeutic-based treatments for DIPG. Thus, it is mandatory to “warm” these tumors in order to implement a successful immunotherapy for DIPGs.

Delta24-RGD is an oncolytic adenovirus currently being tested in clinical studies for the treatment of brain tumors, including DIPGs. Delta24-RGD selectively replicates in tumor cells, killing the host cell while spreading more viral particles. Nevertheless, Delta24-RGD triggers an inflammatory environment that “warms” and unmasks the tumor to the immune system. As a result, Delta24-RGD mediates the establishment of an anti-cancer immune response that could eventually be potentiated by immunostimulatory molecules. In this regard, Delta24-RGD can also act as delivery vector to express immunostimulatory molecules in the tumor site enhancing an anti-DIPG immune response while avoiding the risk of systemic toxicity.

Here we propose to develop a Delta24-RGD virus encoding immunostimulatory genes as a comprehensive approach against DIPG, invigorating innate and adaptive arms of the anti-tumor immune response in a single treatment. The dual anti-tumor effect of this virus (oncolysis and immunostimulation) will be assessed in relevant DIPG models. If successful at the end of this project, we will be in the position to propel a phase I/II clinical trial with this new oncolytic virus.