Zebrafish Avatars: a platform for personalized medicine & discovery of innate immune mechanisms & modulators for cancer immunotherapy

In the last years I have been committed to develop and optimize the Patient-derived zebrafish xenograft model or zAvatar-test for personalized medicine and take it to the clinical setting. My strategy has been to establish various zAvatar tumor models, investing efforts in generating protocols to test different therapy options, but more importantly determine the predictive value of our test by performing co-clinical studies. In these clinical studies, the patient’s clinical response to treatment was compared to their matching zAvatar. Predictive accuracy of our test was as high 91% in ovarian and colorectal cancer and 100% in breast cancer (Costa et al Nat. Comm2024, Estrada et submitted, Mendes et al Nature Precision Oncology 2025). These promising results are now leading to a multicentric randomized clinical trial.

In parallel to this translational research, my LAB has another major research arm: to investigate the interplay between tumor cells and innate immunity. How do tumor cells evade and suppress the innate immune system? Can we find new therapies that modulate innate immunity and combine them with adaptive therapies to engage both arms of the immune system to fight cancer? My LAB is tackling these questions, taking advantage of zAvatar model, which allows to focus specifically on the innate immune system and its interactions with human cancer cells, live and with single cell resolution.