Bladder cancer therapy using a conformationally fluid tumoricidal peptide complex.
Antonín Brisuda1, James C S Ho2,3, Pancham S Kandiyal4
1Department of Urology, Motol University Hospital, 2nd Faculty of Medicine, Charles University Praha, Prague, Czech Republic.
Nature Communications
|June 9, 2021
Summary
A novel peptide-based therapy, alpha1-oleate, demonstrates potent tumoricidal activity against bladder cancer. Clinical trials show significant tumor reduction and cell shedding with no adverse effects, offering new hope for patients.
Area of Science:
- Biochemistry
- Molecular Biology
- Oncology
Background:
- Partially unfolded alpha-lactalbumin forms the HAMLET complex with tumoricidal properties.
- There is a significant unmet need in non-muscle invasive bladder cancer due to therapeutic failures and high recurrence rates.
Purpose of the Study:
- To develop and evaluate a peptide-based molecular approach for targeting and killing tumor cells.
- To assess the safety and efficacy of alpha1-oleate in a clinical trial for non-muscle invasive bladder cancer.
Main Methods:
- Formation of alpha1-oleate complex from a 39-residue alpha-helical peptide of alpha-lactalbumin and oleic acid.
- Nuclear magnetic resonance and computational simulations to elucidate structure.
- Phase I/II, single-center, placebo-controlled, double-blinded clinical trial involving intra-vesical instillations of alpha1-oleate.
Main Results:
- Alpha1-oleate treatment resulted in massive shedding of tumor cells and reduced tumor size in bladder cancer patients.
- No drug-related side effects were detected, meeting primary safety and efficacy endpoints.
- Secondary endpoints showed alpha1-oleate in shed cells, tumor apoptosis, and inhibition of cancer-related gene expression.
Conclusions:
- Alpha1-oleate represents a promising peptide-based therapeutic for targeting and eliminating tumor cells.
- The clinical trial results are particularly encouraging for bladder cancer, addressing a critical unmet medical need.
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