MIG

Faculty of Medicine | Lund University

HAMLET, a new concept for cancer therapy

Some years ago, serendipity allowed us to discover HAMLET, a new human molecule that kills cancer cells. Since then, we have characterised the molecule and its mechanism of action and have shown in clinical trials that HAMLET works in patients.

HAMLET is a new drug candidate with astonishing but well-documented properties. 1) HAMLET kills a broad range of tumor cells but spares healthy, mature cells (Proc. Natl. Acad. Sci, 1995 and 2000). 2) HAMLET kills more than 40 different types of tumour cells, including those most difficult to treat with available drugs. 3) HAMLET kills tumour cells by a natural non-toxic mechanism. Thus, unlike most current cancer drugs, HAMLET does not appear to damage healthy tissues. 4) HAMLET occurs naturally in human milk, and may contribute to the lowered cancer incidence in breast-feeding mothers and their children. 5) HAMLET can be produced in large quantities at drug quality.

Our clinical studies have shown that HAMLET is tumoricidal and selective for tumor tissue in vivo as well. HAMLET removed papillomas in a placebo controlled clinical study (New England Journal of Medicine, 2004). In one week, local instillations of HAMLET killed tumor cells in patients with bladder cancer (International Journal of Cancer, 2007). HAMLET treatment also delayed tumor progression and increased survival in a human brain tumor xenograft model, without toxic effects (Cancer Research, 2004).

hamlet jpg

Our work aims to elucidate in detail the molecular basis for HAMLET’s broad tumoricidal activity and for the resistance of healthy differentiated cells. In collaboration with international universities, we hope to understand structure-function relationships of the HAMLET complex. It is also obvious that selective tumour cell death would present an ideal basis for therapy, as healthy tissues and their functions would remain undisturbed. We therefore aim to extend HAMLET therapy to a larger number of tumor models.

Figure shows the change in size of a papillary bladder cancer before HAMLET treatment and one week after HAMLET treatment in a patient.

Change in size of a papillary bladder cancer befor HAMLET treatment and one week after

Group members:

Basiri, Susan

BMA

susan.basiri@med.lu.se

046-2227185

Ho, James

PhD Student

chin_shing.ho@med.lu.se

046-2227185

Nadeem, Aftab

PhD Student

aftab.nadeem@med.lu.se

046-2227185

Puthia, Manoj

Senior Scientist, DVM, PhD

manoj.puthia@med.lu.se

046-2227185

Rydström, Anna

Researcher

anna.rydstrom@med.lu.se

046-2227185

Svanborg, Catharina

Professor

Catharina.Svanborg@med.lu.se

046-2227044

Publication list:

Authors

Title

Journal

Ho Cs J, Storm P, Rydstrom A, Bowen B, Alsin F, Sullivan L, Ambite I, Mok KH, Northen T,Svanborg C.J

Lipids as Tumoricidal Components of Human Alpha-lactalbumin Made Lethal to Tumor Cells (HAMLET); Unique and Shared Effects on Signaling and Death.

Biol Chem. 2013 Jun 14;288(24):17460-71.

Wegmann F, Gartlan KH, Harandi AM, Brinckmann SA, Coccia M, Hillson WR, Kok WL, Cole S, Ho LP, Lambe T, Puthia M, Svanborg C, Scherer EM, Krashias G,Williams A, Blattman JN, Greenberg PD, Flavell RA, Moghaddam AE, Sheppard NC, Sattentau QJ.

Polyethyleneimine is a potent mucosal adjuvant for viral glycoprotein antigens.

Nat Biotechnol. 2012 Aug 26.

Storm P, Aits S, Puthia MK, Urbano A, Northen T, Powers S, Bowen B, Chao Y, Reindl W, Lee DY, Sullivan NL, Zhang J, Trulsson M, Yang H, Watson JD, Svanborg C.

Conserved features of cancer cells define their sensitivity to HAMLET-induced death; c-Myc and glycolysis.

Oncogene. 2011 Jun 6.

Hakansson AP, Roche-Hakansson H, Mossberg AK, Svanborg C.

Apoptosis-like death in bacteria induced by HAMLET, a human milk lipid-protein complex.

PLoS One. 2011 Mar 10;6(3):e17717.

Trulsson M, Yu H, Gisselsson L, Chao Y, Urbano A, Aits S, Mossberg AK, Svanborg C.

HAMLET binding to α-actinin facilitates tumor cell detachment. 

PLoS One. 2011 Mar 8;6(3):e17179.

Mossberg AK, Hun Mok K, Morozova-Roche LA, Svanborg C.

Structure and function of human α-lactalbumin made lethal to tumor cells (HAMLET)-type complexes.

FEBS J. 2010 Nov;277(22):4614-25. doi: 10.1111/j.1742-4658.2010.07890.x. Review.

Mossberg AK, Puchades M, Halskau Ø, Baumann A, Lanekoff I, Chao Y, Martinez A, Svanborg C, Karlsson R.

HAMLET interacts with lipid membranes and perturbs their structure and integrity.

PLoS One. 2010 Feb 23;5(2):e9384

Mossberg AK, Hou Y, Svensson M, Holmqvist B, Svanborg C.

HAMLET treatment delays bladder cancer development.

J Urol. 2010 Apr;183(4):1590-7. Epub 2010 Feb 21.

Pettersson-Kastberg J, Mossberg AK, 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 Dec 18;394(5):994-1010. Epub 2009 Sep 18.

Gustafsson L, Aits S, Onnerfjord P, Trulsson M, Storm P, Svanborg C

Changes in proteasome structure and function caused by HAMLET in tumor cells.

PLoS One. 2009;4(4):e5229. Epub 2009 Apr 14

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