Summary
CCR8 plays an important role in mediating the recruitment and immunosuppressive function of Treg cells in the tumor microenvironment. IPG7236 is the first small molecule to advance into the clinical stage. It exerts an anti-cancer effect via modulating Treg and CD8+ T cells. Both IPG7236 alone or in combination with PD-1 antibody showed significant tumor suppression effects in the murine xenograft model of human breast cancer. IPG7236 is a promising clinical candidate targeting CCR8 with excellent in vitro ADMET properties, PK as well as safety profiles, and in vivo efficacy. IPG7236 is currently under phase 1 clinical trial for both cancer and upcoming IgG4RD.
Mechanism of Action
￭ CCR8 antagonists inhibit the induction, migration, expansion, and infiltration of tumor-associated Treg cells in tumor tissues, thereby reversing the tumor immunosuppressive microenvironment and enhancing the antitumor immune response.
Key Differentiation
￭ The global first small molecule antagonist targeting the chemokine receptor CCR8.
￭ Potentially safer than CCR8 monoclonal antibodies, particularly with an enhanced Antibody-Dependent Cell-Mediated Cytotoxicity (ADCC) effect antibody.
In vivo Properties
￭ Demonstrated a significant single-digital antitumor activity in MDA-MB-231 (breast cancer) PBMC humanized mice model.
￭ Exhibited a significant synergistic effect on antitumor activity with PD1 antibody (JS001) in human colon and breast cancer of humanized mice model
In vivo
￭ Demonstrated a significant single-digital anti-tumor activity in MDA-MB-231 (breast cancer) PBMC humanized mice model.
*P < 0.05, ***P < 0.001, ****P < 0.0001, compared to the vehicle group
￭ Demonstrated a significant synergistic effect on anti-tumor activity with PD1 antibody (JS001) in human colon and breast cancer of humanized mice model.
*P < 0.05, **P < 0.01, compared to the vehicle group
Publications
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