Targeting CD24 activates macrophages to reduce tumor burden in preclinical models of solid tumors.

Authors

Douglas V Faget, Rachel E Brewer, Joseane Sampaio, Grace Blacker, Giovanni C Forcina, Shefah Qazi, Priyanka R Malusare, Seth Ludwig, Kelsey Hart, Justin M Hansen, Alexandria Beans, Rubeen Virani, Oliver Dorigo, Raphaël Rousseau, Pin-Joe Ko, Jennifer Yinuo Cao, John S Burg, Ravindra Majeti, Irving L Weissman, Amira A Barkal, Roy L Maute, Suzana A Kahn

Published in

Clinical cancer research : an official journal of the American Association for Cancer Research. Jul 21, 2026. Epub Jul 21, 2026.

Abstract

CD24 is a "don't eat me" signal overexpressed across multiple solid tumors and contributes to immune evasion by suppressing macrophage-mediated phagocytosis. Targeting the CD24/Siglec-10 axis represents a novel immuno-oncology strategy to restore innate immune surveillance.
We developed PHST001, a humanized IgG4 monoclonal antibody targeting CD24, and evaluated its activity using in vitro phagocytosis assays, xenograft and immune-competent syngeneic mouse models, and ex vivo systems incorporating human immune cells and tumor samples. Nonclinical safety parameters were assessed to evaluate translational feasibility.
PHST001 binds CD24 with high affinity and blocks Siglec-10 engagement, resulting in enhanced macrophage-mediated phagocytosis across multiple tumor indications and subtypes, inhibition of primary and metastatic tumor growth, and prolonged survival in preclinical models. PHST001 demonstrated a favorable nonclinical safety profile and exhibited anti-tumor activity as both monotherapy and in combination with standard-of-care treatments, including chemotherapy, radiotherapy, and antibody-drug conjugates (ADCs). Antitumor responses were associated with engagement of tissue-resident macrophages, and in syngeneic models, induction of tumor-reactive T-cell responses, supporting a role for CD24 in coordinating innate and adaptive immune suppression.
These findings establish CD24 as a critical regulator of tumor immune evasion and support the clinical development of PHST001 as a CD24-targeted immunotherapy. A Phase I clinical study (NCT06840886) evaluating the safety and tolerability of PHST001 in adult patients with relapsed or refractory solid tumors is ongoing.

PMID:
42478960
Bibliographic data and abstract were imported from PubMed on 21 Jul 2026.

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