The main focus of LABORATORY PROGRAM I will be the determination of the efficacy of B43-PAP against primary blasts from patients enrolled in CLINICAL PROGRAM I, so that the correlation between the clinical response of relapsed B-lineage ALL patients to B43-PAP therapy and immunotoxin sensitivity of primary blasts from the same patients can be examined. To this end, we will examine the anti-leukemic efficacy of B43-PAP against primary blasts from patients enrolled in CLINICAL PROGRAM I using both the in vitro leukemic progenitor cell (LPC) assay system as well as the in vivo SCID mouse model system (SPECIFIC AIM 1). In the proposed studies, we will obtain pretreatment and posttreatment bone marrow aspirate specimens from patients enrolled in CLINICAL PROGRAM I. Our minimal residual leukemia detection assay system will be used to measure the residual LPC burden in these bone marrow specimens (SPECIFIC AIM 2). We will interface this data with the clinical outcome data from CLINICAL PROGRAM I in an attempt to correlate the initial target LPC burden as well as the residual LPC burden on day 14 with the duration of the achieved remission.
Under SPECIFIC AIM 3, we will examine the impact of B43 (anti-CD19)-PAP immunotoxin therapy on the pretransplant residual leukemia burden of high risk remission patients undergoing BMT. It is anticipated that patients whose pretransplant LPC burden is substantially reduced by B43-PAP immunotoxin will have a superior disease-free survival than patients with a high LPC burden who do not receive B43-PAP. Biologic data generated in these in vitro and in vivo model systems will likely improve our ability to predict the B43-PAP immunotoxin response of relapsed B-lineage ALL patients. Therefore, the proposed studies have the potential to generate very valuable information for appropriate assignment of relapsed B-lineage ALL patients to B43-PAP containing reinduction and/or intensification regimens in future trials.
