Human CD30 is a 120 kDa type I transmembrane glycoprotein with three primary domains :
Extracellular domain (ECD): 361 amino acids containing six cysteine-rich repeats critical for ligand binding
Transmembrane domain: 28 amino acids
Cytracellular domain: 188 amino acids with signaling motifs
Two isoforms arise from alternative splicing:
Full-length membrane-bound CD30
A truncated cytoplasmic variant retaining only the C-terminal 132 amino acids
Feature | Human CD30 | Murine CD30 |
---|---|---|
Extracellular length | 361 aa | 263 aa |
Cysteine-rich repeats | 6 | 3 |
Sequence identity | - | 53% (vs. human) |
CD30 exhibits dual roles in immune regulation:
Co-stimulatory signaling: Enhances antigen-induced proliferation of Th0/Th2 cells and cytokine secretion (IL-4, IL-5, IL-13)
Apoptosis regulation:
B cell modulation: Drives CXCR4/CCL5 expression and antibody production
Soluble CD30 (sCD30), generated via TACE-mediated cleavage, acts as a decoy receptor to inhibit membrane CD30 signaling .
CD30 is overexpressed in:
Tumor Type | CD30v+ Cases (%) |
---|---|
B-cell NHL (high grade) | 62.5% |
Multiple myeloma | 100% |
Adult T-cell leukemia | 27.3% |
Elevated serum sCD30 correlates with:
Brentuximab vedotin (anti-CD30 ADC):
FDA indications: Relapsed HL, systemic ALCL, CD30+ mycosis fungoides
Mechanism: Delivers monomethyl auristatin E to CD30+ cells
Therapy Type | Mechanism | Clinical Outcome |
---|---|---|
Bispecific antibodies | CD30×CD3 engagement for T cell activation | 70% ORR in cutaneous ALCL |
Naked anti-CD30 mAbs | Direct tumor targeting | Limited efficacy (CR rate <5%) |
Mature human CD30 consists of:
CD30 plays a crucial role in the regulation of immune responses. It is involved in the activation and proliferation of T cells and B cells, and it can influence the survival and apoptosis of these cells. The interaction of CD30 with its ligand, CD30L (CD30 Ligand/TNFSF8), can lead to the activation of various signaling pathways that are important for immune regulation .
Recombinant human CD30 is produced using recombinant DNA technology, which involves inserting the gene encoding CD30 into a suitable expression system, such as a mouse myeloma cell line (NS0-derived human CD30/TNFRSF8 protein) . This allows for the production of large quantities of CD30 protein for research and therapeutic purposes.
Recombinant CD30 is used in various applications, including:
The study of CD30 and its interactions with CD30L has significant implications for understanding and treating various immune-related diseases. By targeting CD30, researchers and clinicians can develop more effective therapies for conditions such as Hodgkin’s lymphoma, non-Hodgkin’s lymphomas, and other diseases involving abnormal T and B cell activation.