CAR-T-Cell Therapy for Solid Tumors Positive for Fibronectin Extra Domain B

Area of Science:

• Immunology
• Oncology
• Biotechnology

Background:

• CAR-T therapy faces challenges in solid tumors due to a lack of specific targets.
• Fibronectin extra domain B (EDB-FN) is identified as a potential target, expressed in tumor and embryonic tissues.
• Previous development of antibody-cytokine fusion proteins targeting EDB-FN suggests its therapeutic potential.

Purpose of the Study:

• To evaluate the therapeutic efficacy of BBz CAR-engineered T-cells targeting EDB-FN in solid tumors.
• To assess the in vitro and in vivo anti-tumor and anti-angiogenic activities of these CAR-T cells.
• To investigate the potential of EDB-FN as a target for CAR-T therapy in solid malignancies.

Main Methods:

• Construction of a BBz CAR targeting EDB-FN and its expression in T-cells via lentiviral transduction.
• In vitro assessment of CAR-T cell activation, cytotoxicity against EDB-FN-positive and -negative cell lines, and cytokine release.
• In vivo evaluation of CAR-T cell efficacy in inhibiting tumor progression and reducing tumor angiogenesis in a mouse model, alongside toxicity assessments.

Main Results:

• CAR-T cells demonstrated specific activation, cytokine release, and lysis of EDB-FN-positive cells (U-87 MG, A549, HUVECs) in vitro, with no toxicity to EDB-FN-negative cells (MCF-7).
• In vivo studies showed that CAR-T cells significantly inhibited U-87 MG tumor growth and reduced tumor vascularization without causing significant organ toxicity.
• Enhanced anti-tumor activity was observed when CAR-T cells were engineered to overexpress a BiTE targeting EDB-FN.

Conclusions:

• CAR-T cells targeting EDB-FN exhibit specific anti-tumor and anti-angiogenic effects both in vitro and in vivo.
• EDB-FN represents a promising therapeutic target for CAR-T cell-based treatment of solid tumors.
• Further development of EDB-FN-targeted CAR-T therapies holds potential for improving solid tumor treatment outcomes.