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Targeting CD38 in Neoplasms and Non-Cancer Diseases
Wojciech Szlasa1, Jakub Czarny2, Natalia Sauer3
1Faculty of Medicine, Wroclaw Medical University, 50-367 Wroclaw, Poland.
Abstract:
CD38 is a myeloid antigen present both on the cell membrane and in the intracellular compartment of the cell. Its occurrence is often enhanced in cancer cells, thus making it a potential target in anticancer therapy. Daratumumab and isatuximab already received FDA approval, and novel agents such as MOR202, TAK079 and TNB-738 undergo clinical trials. Also, novel therapeutics such as SAR442085 aim to outrank the older antibodies against CD38. Multiple myeloma and immunoglobulin light-chain amyloidosis may be effectively treated with anti-CD38 immunotherapy. Its role in other hematological malignancies is also important concerning both diagnostic process and potential treatment in the future. Aside from the hematological malignancies, CD38 remains a potential target in gastrointestinal, neurological and pulmonary system disorders. Due to the strong interaction of CD38 with TCR and CD16 on T cells, it may also serve as the biomarker in transplant rejection in renal transplant patients. Besides, CD38 finds its role outside oncology in systemic lupus erythematosus and collagen-induced arthritis. CD38 plays an important role in viral infections, including AIDS and COVID-19. Most of the undergoing clinical trials focus on the use of anti-CD38 antibodies in the therapy of multiple myeloma, CD19- B-cell malignancies, and NK cell lymphomas. This review focuses on targeting CD38 in cancer and non-cancerous diseases using antibodies, cell-based therapies and CD38 inhibitors. We also provide a summary of current clinical trials targeting CD38.
Insights
CD38 targeting therapies, including antibodies and inhibitors, show promise for treating various cancers and non-cancerous diseases like autoimmune disorders and viral infections. Current clinical trials focus on multiple myeloma and other hematological malignancies.
Area of Science:
- Immunology
- Oncology
- Pharmacology
Background:
- CD38 is a myeloid antigen upregulated in cancer cells, making it a therapeutic target.
- Approved anti-CD38 therapies like Daratumumab are effective in hematological malignancies.
- CD38's role extends beyond cancer to autoimmune and viral diseases.
Purpose of the Study:
- To review the therapeutic potential of targeting CD38 in both cancerous and non-cancerous conditions.
- To summarize ongoing clinical trials investigating novel CD38-targeting agents.
- To explore diverse therapeutic strategies including antibodies, cell-based therapies, and inhibitors.
Main Methods:
- Literature review of current research on CD38 targeting.
- Analysis of FDA-approved and investigational anti-CD38 therapies.
- Summary of clinical trial data for CD38-targeted treatments.
Main Results:
- Anti-CD38 immunotherapies are effective for multiple myeloma and immunoglobulin light-chain amyloidosis.
- CD38 is a potential biomarker for renal transplant rejection and a target in autoimmune diseases.
- CD38 plays a role in viral infections such as AIDS and COVID-19.
Conclusions:
- Targeting CD38 offers a promising therapeutic strategy for a wide range of diseases.
- Further research and clinical trials are essential to fully realize CD38's therapeutic potential.
- Novel CD38 inhibitors and antibodies are advancing treatment options for hematological and non-hematological conditions.
