Generating CAR-macrophages to target endothelin B receptor-positive tumors

Area of Science:

• Immunotherapy
• Oncology
• Cellular Therapy

Background:

• The endothelin axis is overexpressed in various tumors, presenting a potential therapeutic target.
• Current immunotherapy approaches, including CAR-T cells, face challenges in treating solid tumors.
• CAR-macrophages offer a promising alternative for solid tumor treatment, but therapeutic targets are limited.

Purpose of the Study:

• To investigate the efficacy of CAR-macrophages targeting the endothelin B receptor (ET_B) for melanoma treatment.
• To develop and evaluate CAR-macrophages using Rendomab B4 (RB4) antibody targeting ET_B.

Main Methods:

• Characterization of the scFv RB4 fragment derived from the RB4 antibody targeting ET_B.
• Development of CAR-macrophages utilizing the scFv RB4 fragment.
• Evaluation of CAR RB4-macrophage antitumor activity against ET_B-positive and ET_B-low melanoma cell lines.

Main Results:

• The scFv RB4 fragment demonstrated exclusive recognition of ET_B-positive melanoma cell lines.
• CAR RB4-macrophages exhibited significant antitumor activity against high ET_B-expressing WM266 melanoma cells.
• No significant antitumor activity was observed against low ET_B-expressing A375 melanoma cells.

Conclusions:

• This study provides the first proof of concept for CAR therapy targeting the endothelin axis.
• CAR RB4-macrophages represent a promising therapeutic candidate for treating ET_B-positive solid tumors.
• Targeting the endothelin axis with CAR-macrophages offers a novel strategy for solid tumor immunotherapy.