CD44v9

Class

CD44v9-directed antibody-drug conjugate (topoisomerase I inhibitor payload, belotecan derivative KL610023)

Pathway

Humanized anti-CD44v9 IgG1 antibody delivers topoisomerase I inhibitor payload to CD44v9-overexpressing tumor cells (cancer stem cell marker)

CD44v9 is a variant form of CD44, a cell-surface protein that normally helps cells adhere to surrounding tissue and to a matrix molecule called hyaluronic acid. Through alternative splicing, tumor cells can produce isoforms of CD44 that include extra segments, and CD44v9 is one such variant that is enriched on cancer stem cells—a subpopulation of tumor cells thought to drive relapse and resistance to conventional therapy. CD44v9 helps these cells manage oxidative stress by stabilizing a transporter that supplies raw material for the antioxidant glutathione, giving them a survival advantage under the stress of chemotherapy or radiation. Because CD44v9 is much more abundant on tumor and cancer stem cells than on most normal tissue, it serves as a docking point for an antibody-drug conjugate: an antibody that recognizes CD44v9 is chemically linked to a cytotoxic payload, in this case a topoisomerase I inhibitor derived from belotecan. After the antibody binds and the complex is taken into the cell, the payload is released and damages DNA, killing the cell. This approach is being explored across cancers where CD44v9-expressing, stem-like tumor cell populations are implicated in resistance and recurrence, such as gastrointestinal malignancies.