Tumor-agnostic cancer therapy using antibodies targeting oncofetal chondroitin sulfate
Molecular similarities between embryonic and malignant cells can be exploited to target tumors through specific signatures absent in healthy adult tissues. One such embryonic signature tumors express is oncofetal chondroitin sulfate (ofCS), which supports disease progression and dissemination in cancer. Here, we report the identification and characterization of phage display-derived antibody fragments recognizing two distinct ofCS epitopes. These antibody fragments show binding affinity to ofCS in the low nanomolar range across a broad selection of solid tumor types in vitro and in vivo with minimal binding to normal, inflamed, or benign tumor tissues. Anti-ofCS antibody drug conjugates and bispecific immune cell engagers based on these targeting moieties disrupt tumor progression in animal models of human and murine cancers. Thus, anti-ofCS antibody fragments hold promise for the development of broadly effective therapeutic and diagnostic applications targeting human malignancies.
Authors
- Tobias Gustavsson (ORCID: https://orcid.org/0000-0001-9798-5632)
- Felix Goerdeler (ORCID: https://orcid.org/0000-0002-7190-9145)
- Ana R. Colaço
- Caroline Løppke (ORCID: https://orcid.org/0000-0003-0679-5118)
- Sai Sundar Rajan Raghavan (ORCID: https://orcid.org/0000-0002-2575-2685)
- Agnieszka Martowicz (ORCID: https://orcid.org/0000-0002-5781-9995)
- Dominik Georg Friedrich Wolf (ORCID: https://orcid.org/0000-0002-4761-075X)
- Mette Ø. Agerbæk (ORCID: https://orcid.org/0000-0001-5865-2034)
- Morten A. Nielsen (ORCID: https://orcid.org/0000-0003-2668-4992)
- Maj Sofie Ørum-Madsen
- Thomas Lavstsen (ORCID: https://orcid.org/0000-0002-3044-4249)
- Mie A. Nordmaj (ORCID: https://orcid.org/0000-0001-5312-3432)
- Swati Choudhary (ORCID: https://orcid.org/0000-0001-5928-8529)
- Mads Daugaard (ORCID: https://orcid.org/0000-0001-8383-055X)
- Lara Duvnjak (ORCID: https://orcid.org/0009-0005-4540-3764)
- Nader Al-Nakouzi (ORCID: https://orcid.org/0000-0002-4653-2884)
- Agnès Garcias López (ORCID: https://orcid.org/0000-0001-5505-6376)
- Irina Nelepcu (ORCID: https://orcid.org/0000-0002-9208-6934)
- Htoo Zarni Oo (ORCID: https://orcid.org/0009-0009-8514-2713)
- Shona Caroline Willis
- Robert Dagil (ORCID: https://orcid.org/0000-0002-5594-0716)
- Kaituo Wang (ORCID: https://orcid.org/0000-0002-5922-7109)
- Henrik Clausen (ORCID: https://orcid.org/0000-0002-0915-5055)
- Thor G. Theander (ORCID: https://orcid.org/0000-0002-3509-7514)
- Elena Ethel Vidal-Calvo (ORCID: https://orcid.org/0000-0001-9655-2106)
- Richard Karlsson (ORCID: https://orcid.org/0000-0003-0448-6135)
- Michael Wierer (ORCID: https://orcid.org/0000-0002-0356-5571)
- Ismail Gögenür (ORCID: https://orcid.org/0000-0002-3753-268X)
- Yen‐Hsi Chen (ORCID: https://orcid.org/0000-0001-9484-3145)
- Rebecca L. Miller (ORCID: https://orcid.org/0000-0001-8574-1948)
- Ali Salanti (ORCID: https://orcid.org/0000-0003-2207-5575)
- Mona Marzban
- Yong Wang (ORCID: https://orcid.org/0000-0001-9156-0377)
- Yuzhuo Z. Wang (ORCID: https://orcid.org/0000-0002-9749-8591)
- Amalie M. Jørgensen (ORCID: https://orcid.org/0000-0002-8554-7261)
- Thomas Mandel Clausen (ORCID: https://orcid.org/0000-0001-7543-9622)
- Anne Martin-Salazar (ORCID: https://orcid.org/0009-0003-3831-8225)
- Joana Mujollari (ORCID: https://orcid.org/0009-0004-1809-0929)
- Ann Skafte (ORCID: https://orcid.org/0009-0006-1024-2224)
- Jan Oberkofler
- Daria Ropac
Institutions
- University of Copenhagen (DK)
- Vancouver Coastal Health (CA)
- University of British Columbia (CA)
- Universität Innsbruck (AT)
- Copenhagen University Hospital (DK)
- Tyrolean Cancer Research Institute (AT)
- Ferring Pharmaceuticals (Denmark) (DK)
- CS Diagnostics (DE)
- Vancouver Coastal Health Research Institute (CA)
- Zealand University Hospital Køge (DK)
- Zhejiang University (CN)
Publication Details
- Journal
- Nature Communications
- Published
- 2024-08-30
- DOI
- https://doi.org/10.1038/s41467-024-51781-0
- Citations
- 21
- Primary Topic
- Glycosylation and Glycoproteins Research
- Type
- article
- Field-Weighted Citation Impact
- 4.91
Funders
- European Molecular Biology Organization
- Innovationsfonden
- Danmarks Grundforskningsfond
- Carlsbergfondet
- Lundbeckfonden
- Novo Nordisk
- Novo Nordisk Fonden
- Canadian Institutes of Health Research