/ News, Research
Combining Forces: Fusion Protein Boosts Immune Attack on Cancer (Zippelius Lab)
Harnessing the body’s immune system has transformed cancer treatment, yet current immunotherapies are often limited by toxicity or by the ability of tumors to silence immune cells. A new study from Irene Fusi and Clara Serger et al. in Alfred Zippelius’ Cancer Immunology lab, now published in Science Translational Medicine, presents a promising next-generation approach.
The team investigated PD1-IL2v, a fusion protein that combines an interleukin-2 variant (IL-2v) with a PD-1–blocking antibody. This dual-action design not only lifts inhibitory PD-1 signaling but also delivers IL-2v directly to PD-1–positive T cells in the tumor microenvironment.
Using human lung cancer samples and patient-derived tumor fragments, the researchers show that PD1-IL2v:
- Expands proliferative, cytotoxic CD8+ T cells with tumor-reactive transcriptional programs, including up-regulation of CXCR6, which enhances their migratory capacity.
- Drives conventional CD4+ T cells toward a TFH/TH1-like state, marked by elevated CXCL13 expression, a phenotype previously associated with responsiveness to PD-1 blockade.
- Induces multifaceted antitumor effector programs without expanding immunosuppressive Tregs, thereby avoiding a major limitation of conventional IL-2 therapies.
Mechanistic insights from this study highlight how targeted IL-2 delivery can rewire exhausted T cells into potent effectors, boost chemokine-driven migratory capacity, and promote phenotypic features linked to improved cross-talk with other immune populations.
The fusion protein, developed by Roche, is currently under evaluation in a Phase I clinical trial (NCT04303858). According to the authors, these findings pave the way for more effective and less toxic immunocytokine therapies in cancer.
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