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肿瘤与非癌症疾病中的 CD38 靶向

英文原题:Targeting CD38 in Neoplasms and Non-Cancer Diseases.

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Targeting CD38 in Neoplasms and Non-Cancer Diseases.

PubMed 2022/08/28(内容时间) Cancers (Basel) Q2 · IF 4.8(JCR 2025)

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中文摘要

CD38是一种髓系抗原,存在于细胞膜和细胞内区室。它在癌细胞中的表达往往升高,因此可能成为抗癌治疗靶点。达雷妥尤单抗和伊沙妥昔单抗已获FDA批准,MOR202、TAK079和TNB-738等新药正在临床试验中。另有SAR442085等新型疗法旨在超越较早开发的抗CD38抗体。抗CD38免疫治疗可有效治疗多发性骨髓瘤和免疫球蛋白轻链淀粉样变性;CD38在其他血液系统恶性肿瘤的诊断和潜在治疗中也有重要作用。除血液肿瘤外,CD38还是胃肠、神经和呼吸系统疾病的潜在治疗靶点。由于CD38与T细胞上的TCR和CD16有强相互作用,它还可能成为肾移植患者移植物排斥的生物标志物。

此外,在系统性红斑狼疮和胶原诱导性关节炎等非肿瘤疾病中,CD38也发挥作用。CD38还参与艾滋病和COVID-19等病毒感染。目前多数临床试验聚焦于抗CD38抗体治疗多发性骨髓瘤、CD19阴性B细胞恶性肿瘤和NK细胞淋巴瘤。本文综述使用抗体、细胞疗法和CD38抑制剂靶向CD38治疗肿瘤及非肿瘤疾病的研究,并总结当前靶向CD38的临床试验。

展开英文摘要原文

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.

论文信息

作者
Szlasa W、Czarny J、Sauer N、Rakoczy K、Szymańska N、Stecko J、Kołodziej M、Kaźmierczak M
第一作者单位
Faculty of Medicine, Wroclaw Medical University, 50-367 Wroclaw, Poland.Poland
通讯作者单位
Department of Basic Medical Sciences, Faculty of Pharmacy, Wroclaw Medical University, 50-556 Wrocław, Poland.Poland
文献类型
综述
期刊
Cancers2022 Aug 28
原文标识
PubMed 36077708 · DOI 10.3390/cancers14174169