Journal
EXPERT OPINION ON INVESTIGATIONAL DRUGS
Volume 32, Issue 2, Pages 107-125Publisher
TAYLOR & FRANCIS LTD
DOI: 10.1080/13543784.2023.2179482
Keywords
Acute myeloid leukemia; antibody; antibody-drug conjugate; bispecific antibody; CD33; CD47; fusion protein; immunotherapy; LILRB4; targeted therapy
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Acute myeloid leukemia (AML) is a common and deadly leukemia in adults, which is currently managed with non-targeted chemotherapy and stem cell transplants. The identification of tumor-specific cell surface receptors has led to the development of targeted antibody therapies, which are expected to provide personalized and safe treatment options for AML patients.
IntroductionAcute 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.Areas coveredIn 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.Expert opinionOne 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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