The protein-lipid complex alpha1-oleate, derived from HAMLET (Human Alpha-lactalbumin Made LEthal to Tumor cells), is identified as a molecular entity with significant therapeutic potential. Structural characterization of the complex and results of a successful placebo-controlled clinical trial are presented.

2nd Faculty of Medicine Charles University Praha Prague Czech Republic

Department of Urology Motol University Hospital Prague Czech Republic

Division of Microbiology Immunology and Glycobiology Department of Laboratory Medicine Faculty of Medicine Lund University Lund Sweden

Singapore Centre for Environmental Life Sciences Engineering Nanyang Technological University Singapore Singapore

Trinity College Dublin Trinity Biomedical Sciences Institute School of Biochemistry and Immunology Dublin Ireland

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Brisuda A, Ho JCS, Kandiyal PS, Ng JTY, Ambite I, Butler DSC, Háček J, Wan MLY, Tran TH, Nadeem A, et al. Bladder cancer therapy using a conformationally fluid tumoricidal peptide complex. Nat Commun. 2021;12(1):1. doi:10.1038/s41467-021-23748-y. PubMed DOI PMC

Hakansson A, Zhivotovsky B, Orrenius S, Sabharwal H, Svanborg C.. Apoptosis induced by a human milk protein. Proc Natl Acad Sci U S A. 1995;92:8064–3. doi:10.1073/pnas.92.17.8064. PubMed DOI PMC

Svensson M, Hakansson A, Mossberg AK, Linse S, Svanborg C. Conversion of alpha-lactalbumin to a protein inducing apoptosis. Proc Natl Acad Sci U S A. 2000;97:4221–4226. doi:10.1073/pnas.97.8.4221. PubMed DOI PMC

Ho JC, Nadeem A, Rydstrom A, Puthia M, Svanborg C. Targeting of nucleotide-binding proteins by HAMLET–a conserved tumor cell death mechanism. Oncogene. 2016;35:897–907. doi:10.1038/onc.2015.144. PubMed DOI

Nadeem A, Sanborn J, Gettel DL, James HCS, Rydström A, Ngassam VN, Klausen TK, Pedersen SF, Lam M, Parikh AN, et al. Protein receptor-independent plasma membrane remodeling by HAMLET: a tumoricidal protein-lipid complex. Sci Rep. 2015;5:16432. doi:10.1038/srep16432. PubMed DOI PMC

Gustafsson L, Leijonhufvud I, Aronsson A, Mossberg AK, Svanborg C. Treatment of skin papillomas with topical alpha-lactalbumin-oleic acid. N Engl J Med. 2004;350:2663–2672. doi:10.1056/NEJMoa032454. PubMed DOI

Tran TH, Ambite I, Butler D, Wan MLY, Tran TH, Höglund U, Babjuk M, Svanborg C. Bladder cancer therapy without toxicity – a dose-escalation study of alpha1-oleate. Int J Cancer. 2020;147:2479–2492. doi:10.1002/ijc.33019. PubMed DOI

Pettersson-Kastberg J, Mossberg A-K, Trulsson M, Yong YJ, Min S, Lim Y, O’Brien JE, Svanborg C, Mok KH. alpha-Lactalbumin, engineered to be nonnative and inactive, kills tumor cells when in complex with oleic acid: a new biological function resulting from partial unfolding. J Mol Biol. 2009;394:994–1010. doi:10.1016/j.jmb.2009.09.026. PubMed DOI

Antoni S, Ferlay J, Soerjomataram I, Znaor A, Jemal A, Bray F. Bladder cancer incidence and mortality: a global overview and recent trends. Eur Urol. 2017;71:96–108. doi:10.1016/j.eururo.2016.06.010. PubMed DOI

Babjuk M, Böhle A, Burger M, Capoun O, Cohen D, Compérat EM, Hernández V, Kaasinen E, Palou J, Rouprêt M. EAU guidelines on non-muscle-invasive urothelial Carcinoma of the bladder: update 2016. Eur Urol. 2017;71:447–461. doi:10.1016/j.eururo.2016.05.041. PubMed DOI