Targeting Leukemia Stem Cells with the Novel Antibody Drug Conjugate
Koichi Takahashi
MDThe University of Texas MD Anderson Cancer Center
Project Term: July 1, 2024 - June 30, 2027
To improve the cure rate of patients suffering from acute myeloid leukemia (AML), our study aims to target resistant leukemia stem cells by developing an 'antibody-drug conjugate' (ADC) against CD99, a protein expressed on these cells. Initial tests of two ADC versions have shown promise in combating AML. Our next steps involve refining the anti-CD99 antibody, identifying the optimal drug for conjugation, and testing the ADC on patient-derived leukemia models. Completing these objectives will pave the way for a phase 1 clinical trial, offering a potentially transformative treatment for AML.
Despite advancements in targeted therapies for acute myeloid leukemia (AML), a serious blood cancer, the cure rate is still low with many patients relapsing. One reason is a group of stubborn cells called leukemia stem cells, resistant to chemotherapy and capable of self-renewal. Some proteins on these cells are potential therapeutic targets, including CD99.
Previous attempts using antibodies to target CD99 were promising, but had limitations preventing their further development. So, our study aims to improve on this by linking a cancer-killing drug to the anti-CD99 antibody, creating an 'antibody-drug conjugate' (ADC). Initial tests using two versions of anti-CD99 ADCs have shown promising results against AML cells. We now aim to refine the approach by creating a fully humanized anti-CD99 antibody, finding the best drug to attach to it, and testing its effectiveness on patient-derived leukemia models.
Completing these steps will be critical for moving anti-CD99 ADC towards clinical trials, offering a potentially promising new treatment for AML patients. Our ultimate goal is to gather enough data to develop a phase 1 clinical trial for this approach. We've assembled a team of experts to tackle this challenge.