CD30. a transmembrane glycoprotein belonging to the tumor necrosis factor receptor (TNFR) superfamily, is primarily expressed on activated lymphocytes and a hallmark biomarker of classical Hodgkin lymphoma (cHL) and anaplastic large cell lymphoma (ALCL). Its limited expression in normal tissues and upregulated presence in malignant cells make it an attractive therapeutic target.
CD30 antibodies are engineered to selectively bind this antigen, enabling targeted cancer therapies. The first FDA-approved CD30-targeting agent, brentuximab vedotin (2011), is an antibody-drug conjugate (ADC) combining an anti-CD30 monoclonal antibody with the cytotoxic drug monomethyl auristatin E (MMAE). Upon binding CD30-positive cells, the ADC internalizes, releasing MMAE to induce apoptosis. It has shown efficacy in relapsed/refractory cHL and systemic ALCL.
Beyond ADCs, CD30-directed immunotherapies include bispecific antibodies (e.g., linking CD30 to CD16 to engage natural killer cells) and chimeric antigen receptor (CAR) T-cell therapies under investigation. Diagnostic CD30 antibodies are also pivotal in immunohistochemistry to confirm lymphoma subtypes.
Despite success, challenges persist, including variable CD30 expression levels, resistance mechanisms, and toxicity management. Ongoing research explores combination regimens (e.g., with checkpoint inhibitors) and next-generation ADCs to enhance efficacy. CD30 remains a critical paradigm for antibody-based oncology therapeutics, balancing precision targeting with biological complexity.