Summary authored by Adriana Kahn, MD

Drug-based Immunotherapy

Adriana Kahn, MD

It was a pleasure to be selected as a fellow for the Society for Translational Oncology Fellows’Forum 2023 and have direct one-on-one contact with and mentorship advice from the excellent Faculty team. The sessions were all truly outstanding and went way beyond my expectations as they included not only technical scientific content but also guidance for early oncologists on how to navigate the complex but rewarding pathway of clinical investigation and translational work in drug development. We also had broad exposure to Faculty members in different career stages and different settings of practice, which ranged from academia, the FDA and industry. The facultyshared their career trajectories that lead them to be where they are in their careers and the choicesthey made that allowed them to innovate and contribute to the progress of oncology science.

A session that was particularly interesting to me was the lecture from Dr. Azad on clinical and translational research with immunotherapy agents. She shared that the majority of research efforts in drug development are now directed towards immunotherapy, representing 70-75% of the ongoing clinical trials. She reviewed how the surge of immunotherapy agents research happens and the somewhat redundancy on agents that are developed and marketed after one initial drug is successful by the pharmaceutical industry, such as the many drugs acting on PD-1 or PD-L1 pathway, to achieve market space but at the same time maybe not investing enough in novel discoveries. 

We reviewed that the upcoming trials are exploring not only immunotherapy agents alone with novel immune system targets, but also combination therapies with immunotherapy agents among each other or with chemotherapy or targeted agents. We reviewed that this is extremely important and pertinent as one of the hallmarks of cancer is to avoid immune response by dysregulation of our immune response against cancer and therefore restoring our immune system would be beneficial to improve outcomes for patients with many tumor subtypes. We reviewed the currently approved targets for immunotherapy agents and the history of immunotherapy drug development. We discussed that unfortunately many tumors do not respond to these agents or response is not long lasting and this justifies emerging immunotherapy targets that differ in their immune roles and interactions. We discussed how some tumors vary in their immune sensitivity and how we can attempt to modulate them or alter the tumor microenvironment to achieve response to immunotherapy agents, including through the use of drugs that alter tumor epigenetics, like combinations with histone deacetylation or methylation inhibitor agents, or tackling mutations that confer immune resistance, such as the tumors with PIK3CA mutations. For instance, Dr. Azad shared a clinical trial they are developing with the combination of entinostat and immunotherapy, as well as another clinical trial with the PI3K inhibitor copanlisibin association with nivolumab for patients with any tumor type that harbor PIK3CA mutations.

Overall, this lecture was very illustrative and educational, and it truly inspired me to continue to want to make the field move forward by bringing the translational findings into clinical practice.