Tumor Microenvironment Modulating CaCO₃ -Based Colloidosomal Microreactors Can Generally Reinforce Cancer...

Area of Science:

• Biomedical Engineering
• Cancer Immunotherapy
• Nanotechnology

Background:

• Tumor hypoxia and acidity impede cancer immunotherapy by impairing immune cells.
• Solid tumors commonly exhibit these immunosuppressive microenvironments.
• Novel strategies are needed to overcome these challenges in cancer treatment.

Purpose of the Study:

• To develop a multifunctional microreactor for modulating tumor microenvironments.
• To investigate the combined therapeutic effects of the microreactor with existing immunotherapies.
• To enhance the efficacy of immune checkpoint blockade and CAR-T cell therapies.

Main Methods:

• Encapsulation of catalase within calcium carbonate nanoparticle-assembled colloidosomes (CCaP CSs) using a double emulsion method.
• Intratumoral administration of CCaP CSs to neutralize acidity and hypoxia.
• Evaluation of CCaP CSs in combination with anti-PD-1 antibodies and EGFR-CAR-T cells in murine tumor models.

Main Results:

• CCaP CSs effectively scavenged protons, decomposed hydrogen peroxide, and suppressed lactate production.
• Treatment with CCaP CSs activated antitumor immunity and enhanced anti-PD-1 antibody efficacy in CT26 and 4T1 xenografts.
• CCaP CSs significantly improved EGFR-CAR-T cell infiltration and cytokine secretion in a triple-negative breast cancer xenograft model.

Conclusions:

• Chemical modulation of tumor acidity and hypoxia can reverse immunosuppression.
• CCaP CSs represent a promising strategy to potentiate both immune checkpoint blockade and CAR-T cell immunotherapies.
• This approach offers a novel pathway for improving solid tumor treatment outcomes.