Postdoctoral researcher in the Department of Pathology and Immunology (Faculty of Medicine), Maria Cruz Cobo has been awarded a “Knowledge Transfer Grant” from the Swiss 3R Competence Centre (3RCC), which aims to promote methods that replace animal experimentation. This funding will allow her to undertake a research stay at the University of Zurich to refine the alternative techniques used in her project, “Optimizing Patient-Derived Melanoma Organoids as Alternatives to Replace Mouse Tumor-Infiltrating Lymphocyte Models.”

Tumor-infiltrating lymphocyte (TIL) therapy represents a promising form of cellular immunotherapy. It was recently approved for the treatment of recurrent melanoma, achieving durable responses in up to 35% of patients. However, TIL production remains lengthy and often inefficient. Working in the laboratory of Professor Paula Nunes-Hasler, Maria Cruz Cobo’s team has identified new immune-boosting compounds (patent pending) that can double T cell proliferation and increase their activation tenfold. Within an Innosuisse-funded project, the researcher is currently evaluating the effects of these compounds on the expansion and antitumor activity of patient-derived TILs, with the goal of improving adoptive cell therapy.

A human-relevant alternative system

The preclinical models commonly used—syngeneic mice (genetically identical animals), humanized, or immunodeficient mice—present major limitations for TIL studies: murine TIL growth is poor, while human TILs can induce toxicity in immunodeficient mice, complicating data interpretation. To overcome these limitations, Maria Cruz Cobo’s team proposes to develop a human-relevant alternative system.

With 3RCC support, the researchers will learn and implement three-dimensional (3D) patient-derived melanoma cultures or organoids, which preserve key features of the tumor microenvironment, including stromal and immune components. This ex vivo model will enable functional assessment of TIL infiltration, activation, and cytotoxicity in a physiologically relevant context, offering a credible alternative to animal models. In doing so, the project will contribute to the replacement and reduction of animal use, while accelerating the development of more effective TIL-based therapies.