Department of Pharmacotherapy & Translational Research, Center for Pharmacogenomics, College of Pharmacy, University of Florida, Gainesville, FL 32610, USA.
Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
Future Oncol. 2021 Jan;17(3):263-277. doi: 10.2217/fon-2020-0746. Epub 2020 Dec 24.
The aim of this study was to establish the therapeutic relevance of the CD33 isoform by developing novel antibodies targeting the IgC domain of CD33. Two novel IgC-targeting antibodies, HL2541 and 5C11-2, were developed, and CD33 isoforms were assessed using multiple assays in cells overexpressing either CD33 or CD33 isoforms, unmodified acute myeloid leukemia (AML) cell lines and primary AML specimens representing different genotypes for the CD33 splicing single nucleotide polymorphism. CD33 was recognized on cells overexpressing CD33 and unmodified AML cell lines; however, minimal/no cell surface detection of CD33 was observed in primary AML specimens. Both isoforms were detected intracellularly using novel antibodies. Minimal cell surface expression of CD33 on primary AML/progenitor cells warrants further studies on anti-CD33 immunotherapeutics.
本研究旨在通过开发针对 CD33 IgC 结构域的新型抗体来确定 CD33 同种型的治疗相关性。开发了两种新型的 IgC 靶向抗体 HL2541 和 5C11-2，并使用多种检测方法在过表达 CD33 或 CD33 同种型、未经修饰的急性髓细胞白血病 (AML) 细胞系以及代表 CD33 剪接单核苷酸多态性不同基因型的原发性 AML 标本中评估 CD33 同种型。在过表达 CD33 和未经修饰的 AML 细胞系中，CD33 可被识别；然而，在原发性 AML 标本中仅观察到 CD33 的细胞表面检测最小/无。两种同种型均使用新型抗体在细胞内检测到。在原发性 AML/祖细胞上 CD33 的细胞表面表达最小，需要进一步研究抗 CD33 免疫疗法。
