GPNMB

Class

Antibody-drug conjugate (Auristatin S payload)

Notes

Source: https://aacrjournals.org/cancerres/article/86/7_Supplement/1673/781599/ ; https://www.pfizerclinicaltrials.com/find-a-trial/nct07519655-non-small-cell-lung-trial (PF-08046033; researched 2026-08-08)

GPNMB (glycoprotein non-metastatic melanoma protein B) is a transmembrane glycoprotein present at low levels on many normal tissues but expressed at markedly higher density on the surface of several solid tumor types, including melanoma, breast cancer, and glioblastoma, and on some tumor-associated macrophages. Because its expression is enriched on malignant or tumor-supportive cells relative to healthy tissue, it can serve as a docking site for antibody-drug conjugates (ADCs), a drug class that pairs a tumor-targeting antibody with a cytotoxic payload joined by a chemical linker. The antibody binds GPNMB on the cell surface, the complex is drawn into the cell, and intracellular processing releases the payload, in this case an auristatin-class agent, which disrupts microtubule assembly and halts cell division. This targeting strategy aims to concentrate a highly potent cytotoxic agent within GPNMB-expressing tumor cells while limiting exposure of normal tissue, addressing the narrow therapeutic window that otherwise restricts use of such potent agents as conventional systemic chemotherapy. GPNMB-directed ADCs are being explored across solid tumors where elevated GPNMB expression has been documented, reflecting the broader rationale of using tumor-enriched surface antigens to deliver antimitotic drugs selectively.