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Antimicrobial Peptides Induce Cell Death in Marginal Zone Lymphoma Models Resistant to Targeted Therapies

Filippo Spriano1, Alberto J Arribas1, Fangwen Zhang1

  • 1Faculty of Biomedical Sciences Institute of Oncology Research (IOR) USI Bellinzona Switzerland.

Ejhaem
|June 8, 2026
PubMed
Abstract

Insights

Antimicrobial peptides show promise for treating drug-resistant marginal zone lymphoma (MZL). These peptides effectively kill MZL cells, including resistant types, by disrupting cell membranes without causing significant toxicity to normal cells.

Area of Science:

  • Hematology
  • Immunology
  • Drug Discovery

Background:

  • Marginal zone lymphoma (MZL) is an incurable B-cell malignancy.
  • Current treatments like BTK and PI3K inhibitors often fail due to resistance or toxicity.
  • Antimicrobial peptides (AMPs) are innate immunity effectors with selective cytotoxicity against cancer cells.

Purpose of the Study:

  • To evaluate the anti-proliferative and antitumor activity of natural AMPs against MZL cell lines.
  • To assess AMP efficacy in MZL models resistant to established targeted therapies.

Main Methods:

  • Synthesis and testing of seven natural AMPs, including trematocines and temporins.
  • Evaluation of AMPs against MZL cell lines (VL51, Karpas1718) and their drug-resistant derivatives.
  • Determination of cytotoxicity (IC50 values) and assessment of cell death pathways.

Main Results:

  • W-trematocine and temporin L exhibited potent, dose-dependent cytotoxicity (5.7-10 µM IC50) against all MZL models, including resistant ones.
  • AMP-mediated killing involved membrane disruption and non-apoptotic pathways, bypassing conventional resistance mechanisms.
  • W-trematocine demonstrated minimal toxicity to nonmalignant cells, indicating selectivity.

Conclusions:

  • Natural AMPs, particularly W-trematocine and temporin L, are promising candidates for treating drug-resistant MZL.
  • AMPs offer a potential therapeutic strategy for relapsed/refractory MZL by overcoming existing resistance.
  • Further preclinical validation and optimization of AMPs are warranted.
Keywords:
BTKchionodracineslymphomapeptidesresistancetemporinstrematocines

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