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hi my name is cole de golier im a phd candidate in the immunology graduate program at the university of colorado on chutes medical campus im in the laboratory of dr terry fry and im going to talk to you today about how rational modifications to the car antigen binding domain can improve sensitivity to low density target antigens so chimeric antigen receptor or car t cells as most of you probably know are a very effective therapy for leukemias and hematologic malignancies in general on the left here you can see that in this trial and others that cars have a seventy to ninety percent rate of remission induction when used to treat v-lineage leukemias so in a anti-cd22 car trial led by terry at the nci found that patients that relapsed often still had c22 positive leukemia and so this is in contrast to what had been seen in previous trials targeting such as those targeting the cd19 antigen where relapses were cd19 negative so this trial they saw that patients relapse with cd22 positive