Antibody therapies for the treatment of acute myeloid leukemia: exploring current and emerging therapeutic targets

奥佐美星 医学 髓系白血病 CD33 抗体-药物偶联物 嵌合抗原受体 抗体 临床试验 免疫学 免疫疗法 免疫系统 干细胞 单克隆抗体 内科学 生物 川地34 遗传学
作者
Joshua W Morse,Margarita Ríos,John Ye,Adan Rios,Cheng Cheng Zhang,Naval Daver,Courtney D. DiNardo,Ningyan Zhang,Zhiqiang An
出处
期刊:Expert Opinion on Investigational Drugs [Informa]
卷期号:32 (2): 107-125
标识
DOI:10.1080/13543784.2023.2179482
摘要

Acute myeloid leukemia (AML) is the most common and deadly type of leukemia affecting adults. It is typically managed with rounds of non-targeted chemotherapy followed by hematopoietic stem cell transplants, but this is only possible in patients who can tolerate these harsh treatments and many are elderly and frail. With the identification of novel tumor-specific cell surface receptors, there is great conviction that targeted antibody therapies will soon become available for these patients.In this review, we describe the current landscape of known target receptors for monospecific and bispecific antibody-based therapeutics for AML. Here, we characterize each of the receptors and targeted antibody-based therapeutics in development, illustrating the rational design behind each therapeutic compound. We then discuss the bispecific antibodies in development and how they improve immune surveillance of AML. For each therapeutic, we also summarize the available pre-clinical and clinical data, including data from discontinued trials.One antibody-based therapeutic has already been approved for AML treatment, the CD33-targeting antibody-drug conjugate, gemtuzumab ozogamicin. Many more are currently in pre-clinical and clinical studies. These antibody-based therapeutics can perform tumor-specific, elaborate cytotoxic functions and there is growing confidence they will soon lead to personalized, safe AML treatment options that induce durable remissions.
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