A study published in the Journal of Experimental and Clinical Cancer Research investigates the L19IL2 immunotherapy mechanism of action against B-cell lymphoma. This study reveals that L19IL2 slow tumor growth by enhancing intratumoral CD8⁺ T cell priming and cytotoxicity, and dynamically boosting tumor-directed motility.
B cell lymphoma is a common blood cancer affecting thousands of people worldwide each year. While standard approaches such as R-CHOP chemoimmunotherapy and cellular therapies have improved the outcome of the disease, many patients still relapse or develop therapy resistance. In this study, we characterized the mechanism of action of L19IL2, a novel therapeutic strategy designed to selectively activate the immune response in the areas surrounding the tumor. L19IL2, is formed by a fusion between an antibody (L19) that specifically recognizes an antigen expressed in the tumor environment, and interleukin-2 (IL2), a powerful inflammatory cytokine. By delivering IL2 directly to the lymphoma site, this approach aims to activate antitumoral immune cells exactly and only where they are needed, while limiting unwanted off-target effects. Using a preclinical murine model of B cell lymphoma, we found that targeted IL2 delivery significantly slows tumor growth. Importantly, we discovered that this treatment enhances the activity and motility of CD8⁺ T cells, allowing them to better navigate the tumor and to eliminate cancer cells. These findings provide new insight into how precise immune stimulation can improve anti-lymphoma responses and support further clinical development of this strategy for patients with aggressive diseases. This Innosuisse funded project was carried out in collaboration with the Junqueira’s and Sallusto’s lab at the IRB and the biotech company Philochem.
Tumor-targeted IL2 promotes specific CD8(+) T cells private clonal expansion enhancing lymphoma control
Virgilio, T. Chahine, K. Bansal, H. Pizzichetti, C. Renner, L. L. Capucetti, A. Bilato, G. Latino, I. Morone, D. Pulfer, A. Ventura, P. Mele, F. Puca, E. Mangani, D. Junqueira, C. Sallusto, F. Neri, D. De Luca, R. Gonzalez, S. F.
in J Exp Clin Cancer Res (2026) Vol. pp
L19IL2 treatment enhances T cell motility and spatial behavior in lymphoma tumor lesions.
