Fuente: PubMed "nature biotechnology" Transplant Cell Ther. 2026 Jul 30:S2666-6367(26)00594-4. doi: 10.1016/j.jtct.2026.07.032. Online ahead of print.ABSTRACTAdoptively transferred T cells require cytokine stimulation, which is achieved using lymphodepleting chemotherapy with or without administration of exogenous interleukin 2 (IL-2). Lymphodepleting chemotherapy (LDC) is associated with cytopenias and attendant complications, while high dose IL-2 causes severe infusion toxicity and can stimulate undesirable cell populations. To address these challenges, we developed cis-targeted IL-2 fusion molecules which are comprised of an IL-2 mutein with attenuated binding to IL-2Rα and IL-2Rβ linked to an antibody that targets a cell-surface molecule expressed specifically on engineered T cells. Using T cells from healthy donors as well as from lymphoma and melanoma patients, we selectively stimulated CAR-T cells or engineered TILs and enhanced their anti-tumor function in multiple tumor models. We also showed that cis-targeted IL-2 can mediate CART expansion and B cell aplasia in the absence of lymphodepletion in a non-human primate model.PMID:42532276 | DOI:10.1016/j.jtct.2026.07.032