Texas Therapeutics Institute, Brown Foundation Institute of Molecular Medicine, The University of Texas Health Science Center at Houston, Houston, Texas, USA.
Gorgas Memorial Institute of Health Studies, Panama City, Panama.
Expert Opin Investig Drugs. 2023 Feb;32(2):107-125. doi: 10.1080/13543784.2023.2179482. Epub 2023 Feb 26.
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.
急性髓系白血病（AML）是影响成年人的最常见和最致命的白血病类型。它通常通过非靶向化疗的多个疗程来治疗，然后进行造血干细胞移植，但只有能够耐受这些苛刻治疗的患者才能进行移植，而许多患者年龄较大且身体虚弱。随着新型肿瘤特异性细胞表面受体的鉴定，人们坚信针对这些患者的靶向抗体疗法很快就会问世。
在这篇综述中，我们描述了用于 AML 的单特异性和双特异性抗体治疗的已知靶受体的现状。在这里，我们描述了每种受体和正在开发的靶向抗体治疗药物，并说明了每种治疗药物背后的合理设计。然后，我们讨论了正在开发的双特异性抗体以及它们如何改善 AML 的免疫监测。对于每种治疗药物，我们还总结了可用的临床前和临床数据，包括已停止的试验的数据。
一种抗体治疗药物已被批准用于 AML 治疗，即 CD33 靶向抗体药物偶联物 gemtuzumab ozogamicin。目前还有更多的药物正在进行临床前和临床试验。这些抗体治疗药物可以进行肿瘤特异性、复杂的细胞毒性作用，人们越来越有信心，它们将很快为 AML 患者提供个性化、安全的治疗选择，诱导持久缓解。
