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December 8, 2025Blood

Enhancing immunotherapy efficacy in myeloma with a novel dual-action mitochondrial toxic peptide that overcomes resistance and induces immunogenic cell death.

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Authors

CCColin CreanHLHolly LeeKLKelvin P. Lee

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Overview

Novel peptide PP-k improves T cell activation and induces immunogenic cell death in multiple myeloma, suggesting enhanced therapeutic strategies.

Key Points

  • To evaluate the efficacy of the dual-action peptide PP-k in overcoming resistance in multiple myeloma immunotherapy.
  • Tested PP-k in standard multiple myeloma cell lines and resistant variants against Teclistamab.
  • Assessed cytotoxicity using MTS assays and flow cytometry for T cell profiling.
  • Examined the effects on T cell activation via IFN-γ and Granzyme B secretion measurements.
  • Conducted in vivo efficacy studies in NSG mice with implanted human multiple myeloma cells.
  • PP-k demonstrated IC50 values of 8–15 µM across all tested cell lines.
  • Achieved significant tumor elimination in co-culture systems with mouse calvaria.
  • Enhanced T cell activation and cytokine secretion when combined with Teclistamab.
  • Induced mitochondrial disruption and immunogenic cell death in tumor cells.
  • Showed reduced tumor burden in NSG mice injected with PP-k.

Cite This Study

Crean et al. (2025) studied this question.

synapsesocial.com/papers/69362f714fa91c937236e203https://doi.org/10.1182/blood-2025-3924
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