@article{761b91d01f4e460a85f7cd3015e6db1e,
title = "Targeting Human Cancer by a Glycosaminoglycan Binding Malaria Protein",
abstract = "Plasmodium falciparum engineer infected erythrocytes to present the malarial protein, VAR2CSA, which binds a distinct type chondroitin sulfate (CS) exclusively expressed in the placenta. Here, we show that the same CS modification is present on a high proportion of malignant cells and that it can be specifically targeted by recombinant VAR2CSA (rVAR2). In tumors, placental-like CS chains are linked to a limited repertoire of cancer-associated proteoglycans including CD44 and CSPG4. The rVAR2 protein localizes to tumors in vivo and rVAR2 fused to diphtheria toxin or conjugated to hemiasterlin compounds strongly inhibits in vivo tumor cell growth and metastasis. Our data demonstrate how an evolutionarily refined parasite-derived protein can be exploited to target a common, but complex, malignancy-associated glycosaminoglycan modification.",
author = "Ali Salanti and Clausen, {Thomas M.} and Agerb{\ae}k, {Mette O.} and {Al Nakouzi}, Nader and Madeleine Dahlb{\"a}ck and Oo, {Htoo Z.} and Sherry Lee and Tobias Gustavsson and Rich, {Jamie R.} and Hedberg, {Bradley J.} and Yang Mao and Line Barington and Pereira, {Marina A.} and Janine LoBello and Makoto Endo and Ladan Fazli and Jo Soden and Wang, {Chris K.} and Sander, {Adam F.} and Robert Dagil and Susan Thrane and Holst, {Peter J.} and Le Meng and Francesco Favero and Weiss, {Glen J.} and Nielsen, {Morten A.} and Jim Freeth and Nielsen, {Torsten O.} and Joseph Zaia and Tran, {Nhan L.} and Jeff Trent and Babcook, {John S.} and Theander, {Thor G.} and Sorensen, {Poul H.} and Mads Daugaard",
note = "Funding Information: The work was supported by funds from the Novo Nordisk Foundation; the Danish Cancer Society; and Stand Up To Cancer – St. Baldrick{\textquoteright}s Pediatric Dream Team Translational Research Grant (SU2C-AACR-DT1113). Stand Up To Cancer is a program of the Entertainment Industry Foundation administered by the American Association for Cancer Research; Augustinus Foundation; U.S. Department of Defense (DoD); the Harboe Foundation; the European Research Councils (ERC) through the MalOnco program; The Danish Innovation Foundation; VAR2 Pharmaceuticals; Kairos Therapeutics; the Spar Nord Foundation; Team Finn and other riders in the Ride to Conquer Cancer; Safeway; and the Prostate Cancer Canada (PCC) Foundation. A.S., M.D., T.G.T., and P.H.S. are shareholders of VAR2 Pharmaceuticals ApS and members of the board of directors. J.R., B.H., and J.B. are employees of Kairos Therapeutics, Inc. J.F. and J.S. are employees of Retrogenix Ltd. Publisher Copyright: {\textcopyright} 2015 Elsevier Inc.",
year = "2015",
month = oct,
day = "12",
doi = "10.1016/j.ccell.2015.09.003",
language = "English (US)",
volume = "28",
pages = "500--514",
journal = "Cancer Cell",
issn = "1535-6108",
publisher = "Cell Press",
number = "4",
}