Several surface molecules expressed by AML cells have been identified and may be useful for directing tumor-specific immunotherapies. Antibodies against CD33, CD44, CD47, CD123, CD96, CLL-1 and T-cell immunoglobulin mucin-3 (TIM-3) have been tested in preclinical studies. Of these, only CD33 has been validated as an effective target in clinical trials. CD33 is a myeloid-specific sialic acid-binding receptor expressed on the blasts of approximately 90% of AML patients and on AML stem cells. Gemtuzumab ozogamicin, a humanized anti-CD33 monoclonal antibody linked to calicheamicin, was initially approved by the Food and Drug Administration in 2000 due to promising results in relapsed patients. Subsequently, a phase III trial showed no improvement in complete remission or survival rates using chemotherapy plus gemtuzumab ozogamicin compared to the rates achieved with chemotherapy alone. As a consequence, gemtuzumab ozogamicin was voluntarily withdrawn from the market in 2010. However,more recent phase III clinical trials have revisited this and shown benefit in subgroups of patients, leading to a renewed interest in targeting CD33. Interestingly, tumor resistance to gemtuzumab ozogamicin is not driven by down-regulation of CD33 but by chemoresistance to calicheamicin. Patients with CD33+ AML who relapse following treatment with gemtuzumab ozogamicin typically relapse with CD33+ AML, indicating that antigen loss is not a common mode of resistance. CD33-saturating doses of lintuzumab similarly do not lead to down-regulation of the antigen, suggesting that CD33 may be a particularly resilient target for AML immunotherapy.
Drug targets for cancer: CD33 research reagents
Other vital drug targets for cancer likeCD33:
O'Hear C, Heiber JF, Schubert I, Fey G, Geiger TL. Anti-CD33 chimeric antigen receptor targeting of acute myeloid leukemia. Haematologica. 2015;100(3):336-344.