Systemic Immunity Triggered by Boron Neutron Capture Therapy via Manganese-Borate Complex

Area of Science:

• Biomedical Engineering
• Immunotherapy
• Radiochemistry

Background:

• Conventional radiotherapy can impair antitumor immunity due to collateral damage to immune cells.
• Boron neutron capture therapy (BNCT) offers tumor-selective cell killing via 10B (n, α) 7Li reactions, but current agents like boronophenylalanine (BPA) require high doses and show limited immune engagement.
• There is a need for advanced BNCT agents that can enhance immunotherapeutic effects and overcome the limitations of existing treatments.

Purpose of the Study:

• To develop and evaluate a novel biomineralized albumin-based BNCT agent (Albumin@MnB) for enhanced tumor suppression and immunotherapeutic activation.
• To compare the efficacy of Albumin@MnB with the clinical agent BPA at reduced boron doses.
• To investigate the potential of Albumin@MnB to synergize with other immunotherapies, such as adoptive T cell transfer and immune checkpoint inhibitors.

Main Methods:

• Synthesis of Albumin@MnB using clinically accessible borax, manganese, and albumin.
• Evaluation of tumor suppression efficacy in preclinical models, comparing Albumin@MnB with BPA.
• Assessment of intratumoral immune cell infiltration and distant tumor growth inhibition.
• Combination studies with adoptive T cell immunotherapy and immune checkpoint inhibitors.

Main Results:

• Albumin@MnB demonstrated potent tumor suppression at reduced boron doses, outperforming BPA.
• The novel agent significantly enhanced intratumoral immune cell infiltration.
• Albumin@MnB suppressed distant tumor growth, indicating systemic effects.
• Synergistic effects were observed when Albumin@MnB was combined with adoptive T cell immunotherapy and immune checkpoint inhibitors.

Conclusions:

• Albumin@MnB represents a promising advancement in BNCT, offering superior efficacy and reduced boron dosage compared to BPA.
• This agent activates antitumor immunity by integrating targeted radiolysis with metabolic reprogramming and immune activation.
• Albumin@MnB establishes boron neutron capture immunotherapy (BNCI) as a multimodal therapeutic strategy, bridging targeted cell killing with systemic immune responses.