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Drug Target Encyclopedia Series (22) —TNFRSF8

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Release Time：

2025-12-05 14:38

 

  TNFRSF8 (CD30) is a member of the tumor necrosis factor receptor superfamily (TNFRSF), primarily expressed on activated T and B cells, as well as in Hodgkin and Reed–Sternberg cells of Hodgkin lymphoma and anaplastic large cell lymphoma (ALCL).

CD30 has emerged as a validated tumor-associated antigen (TAA) and a leading target in hematologic malignancies, driving the development of antibody-drug conjugates (ADCs), CAR-T cell therapies, and bispecific antibodies.

CD30 is overexpressed in:

• Hodgkin lymphoma (HL)

• Anaplastic large cell lymphoma (ALCL)

• Cutaneous T-cell lymphoma (CTCL)

• Embryonal carcinoma and some solid tumors

Targeting CD30 in cancer immunotherapy:

  • Monoclonal antibodies (mAbs) – e.g., brentuximab (SGN-30) was one of the first to validate CD30 as a therapeutic target.
  • Antibody-drug conjugates (ADCs) – brentuximab vedotin (Adcetris®) remains a clinical success story, achieving durable responses in HL and ALCL.
  • CAR-T cell therapies – CD30-directed CAR-Ts have demonstrated encouraging safety and efficacy profiles in relapsed/refractory lymphomas.
  • Bispecific antibodies (BsAbs) – CD30xCD16A and CD30xCD3 constructs are being investigated to enhance T-cell or NK-cell–mediated cytotoxicity.
  • RNA and mRNA-based therapeutics – Novel mRNA CAR platforms and siRNA strategies targeting CD30 are being explored to expand treatment modalities.

Challenges include:

• Variable CD30 expression across tumor subtypes

• Limited efficacy in CD30-low tumors

• Managing toxicity in combination regimens

🔬Ongoing research is focusing on next-generation CD30-targeted ADCs, dual-antigen CAR-Ts (e.g., CD30/CD70 or CD30/CD123), and combinatorial approaches with checkpoint inhibitors or immunomodulators to enhance durability of response.

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