Scott McComb, Mehdi Arbabi-Ghahroudi, Kevin A Hay, Brian A Keller, Sharlene Faulkes, Michael Rutherford, Tina Nguyen, Alex Shepherd, Cunle Wu, Anne Marcil, Annie Aubry, Greg Hussack, Devanand M Pinto, Shannon Ryan, Shalini Raphael, Henk van Faassen, Ahmed Zafer, Qin Zhu, Susanne Maclean, Anindita Chattopadhyay, Komal Gurnani, Rénald Gilbert, Christine Gadoury, Umar Iqbal, Dorothy Fatehi, Anna Jezierski, Jez Huang, Robert A Pon, Mhairi Sigrist, Robert A Holt, Brad H Nelson, Harold Atkins, Natasha Kekre, Eric Yung, John Webb, Julie S Nielsen, Risini D Weeratna
Chimeric antigen receptor (CAR) T cell therapies targeting B cell-restricted antigens CD19, CD20, or CD22 can produce potent clinical responses for some B cell malignancies, but relapse remains common. Camelid single-domain antibodies (sdAbs or nanobodies) are smaller, simpler, and easier to recombine than single-chain variable fragments (scFvs) used in most CARs, but fewer sdAb-CARs have been reported. Thus, we sought to identify a therapeutically active sdAb-CAR targeting human CD22. Immunization of an adult Llama glama with CD22 protein, sdAb-cDNA library construction, and phage panning yielded >20 sdAbs with diverse epitope and binding properties...
March 21, 2024: Mol Ther Oncol