A tetraspecific engager armed with a non-alpha IL-2 variant harnesses natural killer cells against B cell non-Hodgkin lymphoma
NK cells offer a promising alternative to T cell therapies in cancer. We evaluated IPH6501, a clinical-stage, tetraspecific NK cell engager (NKCE) armed with a non-alpha IL-2 variant (IL-2v), which targets CD20 and was developed for treating B cell non-Hodgkin lymphoma (B-NHL). CD20-NKCE-IL2v boosts NK cell proliferation and cytotoxicity, showing activity against a range of B-NHL cell lines, including those with low CD20 density. Whereas it presented reduced toxicities compared with those commonly associated with T cell therapies, CD20-NKCE-IL2v showed greater killing efficacy over a T cell engager targeting CD20 in in vitro preclinical models. CD20-NKCE-IL2v also increased the cell surface expression of NK cell-activating receptors, leading to activity against CD20-negative tumor cells. In vivo studies in nonhuman primates and tumor mouse models further validated its efficacy and revealed that CD20-NKCE-IL2v induces peripheral NK cell homing at the tumor site. CD20-NKCE-IL2v emerges as a potential alternative in the treatment landscape of B-NHL.
Authors
- Ivan Perrot
- Mathilde Girard-Madoux (ORCID: https://orcid.org/0000-0002-8840-2623)
- Rachel Courtois
- Fabien Chanuc
- Séverine Augier
- Marilyn Giordano
- Gwendoline Grondin
- Justine Galluso
- Éric Vivier (ORCID: https://orcid.org/0000-0001-7022-8287)
- Agnès Représa
- François Le Floch
- Olivier Demaria (ORCID: https://orcid.org/0000-0001-5690-5763)
- Ariane Morel
- Audrey Blanchard Alvarez
- Laura Chiossone (ORCID: https://orcid.org/0000-0002-9097-5869)
- Jean-Baptiste Vallier
- Lucas Rebuffet (ORCID: https://orcid.org/0009-0009-0641-3942)
- Carine Paturel
- Marie Vétizou (ORCID: https://orcid.org/0000-0003-4125-9652)
- William Baron
- Guillaume Habif (ORCID: https://orcid.org/0000-0003-2511-8606)
- Laurent Gauthier (ORCID: https://orcid.org/0000-0003-3225-4825)
- Yannis Morel
- Constance Vagne (ORCID: https://orcid.org/0000-0001-8968-1014)
- Benjamín Rossi (ORCID: https://orcid.org/0000-0001-5523-0602)
- Caroline Denis
- Cécile Bonnafous
- Aurélie Maguer
- Julie Lopez
- Nadia Yessaad
- Romain Remark
- Barbara Carrette
- Marianna Müller
- Léa Simon
Institutions
- Centre National de la Recherche Scientifique (FR)
- Inserm (FR)
- Aix-Marseille Université (FR)
- Université Paris-Saclay (FR)
- Institut Gustave Roussy (FR)
- Innate Pharma (France) (FR)
- Centre d’Immunologie de Marseille-Luminy (FR)
- Hôpital de la Timone (FR)
Publication Details
- Journal
- Science Immunology
- Published
- 2024-11-15
- DOI
- https://doi.org/10.1126/sciimmunol.adp3720
- Citations
- 15
- Primary Topic
- Immune Cell Function and Interaction
- Type
- article
- Field-Weighted Citation Impact
- 3.61