ARM-X: an adaptable mesenchymal stromal cell-based vaccination platform suitable for solid tumors.

Area of Science:

• Immunology
• Cell Biology
• Oncology

Background:

• Mesenchymal stromal cells (MSCs) engineered with the Accum® platform show potential for antigen cross-presentation.
• The first-generation ARM vaccine required high antigen doses for therapeutic effects.
• AccuTOX® was developed as a variant to reduce antigen quantity requirements.

Purpose of the Study:

• To evaluate the efficacy of AccuTOX®-reprogrammed MSCs (ARM-X) as a cancer vaccine.
• To investigate the mechanism of action of AccuTOX® in MSCs.
• To assess the therapeutic potential of ARM-X cells in various solid tumor models.

Main Methods:

• Antigen cross-presentation assays using B3Z T-cell clone.
• Analysis of endosomal escape and antioxidant effects on MSCs.
• In vivo studies in C57BL/6 mice with solid tumors, including depletion studies.
• Validation of findings on human MSCs with immunopeptidome analysis.

Main Results:

• AccuTOX® enables MSCs to cross-present antigens efficiently, even at low doses, while maintaining innate MSC properties.
• Therapeutic administration of ARM-X vaccine combined with anti-PD-1 inhibited tumor growth in melanoma, pancreatic, and colon cancer models.
• The ARM-X vaccine's efficacy depends on efferocytosis and requires both CD4+ and CD8+ T cells.

Conclusions:

• The second-generation ARM-X vaccine is a versatile platform adaptable to multiple solid tumors.
• A direct link exists between AccuTOX®-induced unfolded protein response (UPR) activation and antigen cross-presentation in MSCs.
• UPR stimulation offers a novel strategy to convert MSCs into cellular vaccination tools for various cancer indications.