Related Experiment Video
Updated: Aug 6, 2026
In Vitro Assay to Study Tumor-macrophage Interaction
Published on: August 1, 2019
Targeting CD24 Activates Macrophages to Reduce Tumor Burden in Preclinical Models of Solid Tumors
Douglas V Faget1, Rachel E Brewer1, Joseane Sampaio1
1Pheast Therapeutics Inc., Redwood City, California.
Purpose:
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.
Experimental Design:
We developed PHST001, a humanized IgG4 monoclonal antibody targeting CD24, and evaluated its activity using in vitro phagocytosis assays, xenograft and immunocompetent syngeneic mouse models, and ex vivo systems incorporating human immune cells and tumor samples. Nonclinical safety parameters were assessed to evaluate translational feasibility.
Results:
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 antitumor activity as both monotherapy and in combination with standard-of-care treatments, including chemotherapy, radiotherapy, and antibody-drug conjugates. 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 immunosuppression.
Conclusions:
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.
Insights
PHST001, a novel antibody targeting CD24, enhances macrophage phagocytosis and inhibits tumor growth. This immuno-oncology strategy shows promise for treating solid tumors by restoring innate immune surveillance.
Area of Science:
- Immunology
- Oncology
- Drug Development
Background:
- CD24 acts as a "don't eat me" signal in solid tumors, promoting immune evasion by inhibiting macrophage phagocytosis.
- Targeting the CD24/Siglec-10 pathway offers a novel immuno-oncology approach to reinstate innate immune surveillance against cancer.
Purpose of the Study:
- To develop and evaluate PHST001, a humanized IgG4 monoclonal antibody targeting CD24.
- To assess the preclinical activity and safety of PHST001 in various cancer models.
Main Methods:
- In vitro phagocytosis assays and ex vivo systems with human immune cells and tumor samples.
- In vivo studies using xenograft and immune-competent syngeneic mouse models.
- Nonclinical safety assessments for translational feasibility.
Main Results:
- PHST001 effectively binds CD24, blocks Siglec-10, and enhances macrophage-mediated phagocytosis across diverse tumor types.
- Demonstrated inhibition of primary and metastatic tumor growth, with prolonged survival in preclinical models.
- Favorable nonclinical safety profile; effective as monotherapy and in combination with standard treatments, including ADCs.
Conclusions:
- CD24 is a key regulator of tumor immune evasion, validating PHST001 as a CD24-targeted immunotherapy.
- Preclinical data support the clinical development of PHST001.
- A Phase I clinical trial (NCT06840886) is currently evaluating PHST001 safety and tolerability in patients with relapsed or refractory solid tumors.
