This antibody-based therapy targets blood cancer cells expressing CD33 protein variants that the current immunotherapy fails to recognize. The expression of the protein CD33 is a marker of cancerous white blood cells, making it an excellent target for immunotherapy in acute myeloid leukemia (AML) patients. Each year, there are approximately 20,000 new diagnoses of AML in the United States. The current standard treatment for CD33-positive AML is gemtuzumab ozogamicin. However, the therapy is ineffective in patients expressing a variant T allele, leading to the expression of CD33 variants, CD33 full length (CD33FL) and CD33D2, a CD33 variant lacking the IgV domain. Consequently, patients expressing the CD33D2 variant can't benefit from conventional anti-CD33 immunotherapy.
Researchers at the University of Florida have developed antibodies binding to the IgC-like domain, present in full-length CD33 (CD33FL) and shortened CD33D2. Recognizing and binding to a domain shared between both isoforms can benefit AML patients expressing CD33D2.
Recognizes and targets CD33 isoforms to treat acute myeloid leukemia (AML) and other patients with malignancies
The CD33 antigen is present on the surface of acute myeloid leukemia (AML) cells, making it an excellent marker and target for AML immunotherapy. Conventional AML immunotherapies target the IgV domain coded by exon 2 of CD33 gene. However, some patients present a genetic variation in the splice enhancer region within exon 2 of CD33 gene, resulting in an alternative spliced CD33 isoform lacking IgV domain (CD33D2). Therefore, patients expressing this isoform do not show any clinical benefit from the traditional immunotherapy These antibodies bind CD33 on its constant domain (IgC), found in both CD33FL and CD33D2 isoforms. By enabling the targeting of both CD33 variants, it can provide treatment to a sizeable range of AML patients.
