Genetically modified T cells targeting neovasculature efficiently destroy tumor blood vessels, shrink established...

Area of Science:

• Immunology
• Oncology
• Biotechnology

Background:

• Chimeric antigen receptor (CAR) T cell therapy shows promise for cancer immunotherapy.
• Limited T cell migration and extravasation into tumors hinder in vivo efficacy.
• Targeting tumor neovasculature offers a potential strategy to overcome these limitations.

Purpose of the Study:

• To engineer T cells with a novel CAR incorporating echistatin for targeting tumor vasculature.
• To evaluate the efficacy of these engineered T cells (T-eCAR) in vitro and in vivo.
• To assess the potential of T-eCAR in combination with nanoparticles for enhanced drug delivery.

Main Methods:

• Construction of a CAR incorporating echistatin (eCAR) as a targeting moiety.
• In vitro assessment of T-eCAR's ability to lyse αvβ3 integrin-expressing cells.
• In vivo studies involving systemic administration of T-eCAR in tumor models.
• Evaluation of T-eCAR's effect on tumor growth and nanoparticle deposition.

Main Results:

• T-eCAR efficiently lysed αvβ3 integrin-expressing endothelial and tumor cells in vitro.
• Systemic T-eCAR administration caused tumor-specific bleeding without damaging normal vasculature.
• T-eCAR treatment significantly inhibited the growth of established tumors.
• Co-delivery of T-eCAR with nanoparticles enhanced nanoparticle deposition in tumors.

Conclusions:

• Echistatin-based CAR T cells (T-eCAR) can effectively target and destroy tumor vasculature.
• T-eCAR demonstrates significant anti-tumor activity by disrupting tumor blood supply.
• T-eCAR holds potential for improving targeted cancer therapy and enhancing nanoparticle-mediated drug delivery.