TY - JOUR
T1 - Tumor-agnostic cancer therapy using antibodies targeting oncofetal chondroitin sulfate
AU - Vidal-Calvo, Elena Ethel
AU - Martin-Salazar, Anne
AU - Choudhary, Swati
AU - Dagil, Robert
AU - Raghavan, Sai Sundar Rajan
AU - Duvnjak, Lara
AU - Nordmaj, Mie Anemone
AU - Clausen, Thomas Mandel
AU - Skafte, Ann
AU - Oberkofler, Jan
AU - Wang, Kaituo
AU - Agerbæk, Mette Ø
AU - Løppke, Caroline
AU - Jørgensen, Amalie Mundt
AU - Ropac, Daria
AU - Mujollari, Joana
AU - Willis, Shona
AU - Garcias López, Agnès
AU - Miller, Rebecca Louise
AU - Karlsson, Richard Torbjörn Gustav
AU - Goerdeler, Felix
AU - Chen, Yen-Hsi
AU - Colaço, Ana R
AU - Wang, Yong
AU - Lavstsen, Thomas
AU - Martowicz, Agnieszka
AU - Nelepcu, Irina
AU - Marzban, Mona
AU - Oo, Htoo Zarni
AU - Ørum-Madsen, Maj Sofie
AU - Wang, Yuzhuo
AU - Nielsen, Morten A
AU - Clausen, Henrik
AU - Wierer, Michael
AU - Wolf, Dominik
AU - Gögenur, Ismail
AU - Theander, Thor G
AU - Al-Nakouzi, Nader
AU - Gustavsson, Tobias
AU - Daugaard, Mads
AU - Salanti, Ali
N1 - © 2024. The Author(s).
PY - 2024
Y1 - 2024
N2 - 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.
AB - 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.
KW - Animals
KW - Humans
KW - Chondroitin Sulfates/metabolism
KW - Mice
KW - Neoplasms/immunology
KW - Cell Line, Tumor
KW - Female
KW - Epitopes/immunology
KW - Antigens, Neoplasm/immunology
KW - Xenograft Model Antitumor Assays
KW - Immunoconjugates/therapeutic use
KW - Peptide Library
U2 - 10.1038/s41467-024-51781-0
DO - 10.1038/s41467-024-51781-0
M3 - Journal article
C2 - 39215044
VL - 15
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
IS - 1
M1 - 7553
ER -