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

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.