Antibody targeting of CD24 efficiently retards growth and influences cytokine milieu in experimental carcinomas

Area of Science:

• Oncology
• Immunotherapy
• Cancer Stem Cell Biology

Background:

• CD24 is a highly glycosylated protein overexpressed in many carcinomas, correlating with poor prognosis and marking cancer stem cells in certain cancers.
• CD24 expression influences cancer cell properties and tumor growth.
• Previous studies demonstrated that monoclonal antibody (mAb) SWA11 targeting CD24 effectively retarded tumor growth in vivo.

Purpose of the Study:

• To investigate the molecular mechanisms underlying the therapeutic effects of mAb SWA11.
• To evaluate the anti-proliferative, pro-apoptotic, anti-angiogenic, and microenvironmental impacts of SWA11 treatment in lung and ovarian carcinoma models.

Main Methods:

• Utilized A549 lung and SKOV3ip ovarian carcinoma models in immunodeficient mice (scid/beige and CD1).
• Assessed the effects of SWA11 mAb on tumor cell proliferation, angiogenesis, immune cell infiltration, and the intratumoral cytokine microenvironment.
• Investigated the combination therapy of SWA11 mAb with gemcitabine in the A549 lung cancer model.

Main Results:

• CD24 targeting by SWA11 mAb altered tumor cell proliferation and angiogenesis.
• SWA11 treatment increased immune cell infiltration, suggesting antibody-dependent cell-mediated cytotoxicity (ADCC) involvement.
• Intratumoral cytokine profiles were significantly altered by SWA11 mAb treatment.
• Combination therapy with SWA11 mAb and gemcitabine potentiated anti-cancer efficacy in the A549 lung cancer model.

Conclusions:

• Targeting CD24 with mAb SWA11 demonstrates significant anti-cancer effects.
• CD24 targeting can be a beneficial strategy when combined with standard chemotherapy regimens.