Biomarkers of activity from a phase I study of cergutuzumab amunaleukin in patients with advanced solid tumors

作者：I. Melero, Neeltje Steeghs, Ulrik Lassen, Krisztián Homicskó, Josep Tabernero, Marta Cañamero, Andreas Roller, José Duarte, Eva Rossmann, Galina Babitzki, Nils Grabole, Carl Watson, Christin Habigt, Stefan Evers, David Dejardin, Volker Teichgräber, Jehad Charo · 发表于：Journal for ImmunoTherapy of Cancer · 年份：2026 · DOI：10.1136/jitc-2025-012885 · 被引用次数：1 · 研究领域：CAR-T cell therapy research、Immunotherapy and Immune Responses、Immune Cell Function and Interaction

BACKGROUND: Cergutuzumab amunaleukin (CA) is an immunocytokine comprising an anticarcinoembryonic antigen (CEA) linked to an interleukin-2 (IL-2) variant. CA does not bind to CD25 (IL-2 receptor α) and was designed to maintain the T and natural killer (NK) cell stimulatory effect, while avoiding stimulating effects on regulatory T cells (Tregs). In mouse models, CA previously demonstrated superior tumor targeting to CEA surface expression-positive (CEA+) tumors and increased CD8+ T cells and NK cell numbers in peripheral blood and tumor tissue when compared with wild-type IL-2. We present biomarker data from the first-in-human, open-label, multicenter, phase I, dose-escalation study investigating CA in patients with metastatic/unresectable CEA+ solid tumors (NCT02004106). METHODS: Patients received ascending doses of CA intravenously weekly (qw: 6/10/20 mg) or every 2 weeks (q2w: 10/20/30/40 mg). Flow cytometry determined absolute numbers/mL of CD4+ and CD8+ T cells, NK cells, macrophages/monocytes, Tregs, and B cells and their expression of activation and proliferation markers in circulation. Sequential pretreatment and on-treatment paired tumor biopsies were studied by flow cytometry, multicolor immunohistochemistry, and bulk RNA sequencing. Antitumor activity was used for correlative studies. RESULTS: Biomarker data were collected from 55 patients. After treatment, peripheral blood samples showed increased proliferating NK cells, CD8+ T cells, and CD4+ T cells, without an ...