CD93 blockade promotes effector T-cell infiltration and facilitates adoptive cell therapy in solid tumors

Area of Science:

• Immunology
• Oncology
• Cellular Therapy

Background:

• Adaptive cellular therapy (ACT), including CAR-T cell therapy, shows promise for hematologic cancers but struggles with solid tumor infiltration.
• Poor T-cell trafficking to solid tumors limits the efficacy of current ACT treatments.
• Previous research indicated CD93 targeting normalizes tumor vasculature, enhancing immune checkpoint blockade therapy.

Purpose of the Study:

• To investigate if CD93 blockade can improve ACT efficacy in solid cancers.
• To evaluate the impact of CD93 blockade on effector T-cell infiltration and function in solid tumors.

Main Methods:

• Utilized mouse melanoma models treated with anti-CD93 or anti-IGFBP7 monoclonal antibodies.
• Administered various effector T cells, including CAR-T cells, CD8+OT-1, and pmel-1 T cells.
• Assessed tumor vascular normalization, T-cell infiltration via immunofluorescence and flow cytometry, and the role of adhesion molecules ICAM1 and VCAM1.

Main Results:

• CD93 pathway blockade upregulated adhesion molecules on tumor vasculature, enhancing T-cell infiltration and function.
• Combined T-cell transfer and CD93 blockade synergistically improved tumor vascular maturation and inhibited tumor progression.
• Anti-CD93 treatment selectively promoted effector T-cell infiltration in tumors with upregulated CD93, significantly improving CAR-T therapy outcomes in a solid mouse model.

Conclusions:

• CD93 blockade normalizes tumor vasculature, thereby enhancing effector T-cell infiltration and function in solid cancers.
• The findings support the use of CD93 blockade as a strategy to improve ACT for solid tumors.