CML P01 Core E: GMP- Immune Assessment Core Core Directors: Elizabeth Shpall MD and John McMannis PhD Abstract The primary objective of this POI is to improve the treatment of patients with chronic myelogenous leukemia (CML). Providing speciflc and optimally potent anti-tumor therapy could result in major improvements in antitumor efficacy and safety. In Aim 1, the Good Manufacturing Practice-Immune Assessment (GMP-IA) Core will optimize the clinical procedures for the generation of PRI-specific T cells that target malignant CML cells. The Core will then provide those PRI-specific T cell products to the Project 2 clinical trial in the stem cell transplant setting, in attempt to eradicate minimal residual disease post-transplant. The Core will subsequentiy provide the PRI-specific CTLs to Project 1 in the standard-therapy setting, in attempt to eliminate minimal residual disease in imatinib treated CML patients. The GMP-IA Core Aim 2 will provide manipulated natural killer (NK) cells for the Project 2 stem cell transplantation plus haplo-identical NK cell therapy protocol. Additionally, the GMP-IA Core will evaluate strategies to Improve the NK cell generation procedure, which will be used in later cohorts of that trial. The GMP-IA Core will be responsible for the upscale and validation studies for the clinical cellular products as described above, will aid project investigators preparation of the IND applications, orchestrate the submissions to the Food and Drug Administration (FDA) and communicate with FDA regarding the cellular manipulation procedures. Aim 3 of the GMP-IA Core provides immune assessment of peripheral blood leukocytes from CML patients enrolled in clinical trials of immune mediated therapies in Projects 1 and 2. In the proposed studies, we will measure anti-CML Immunity in patients enrolled in the PR-1 vaccine and PRI-CTL trials to eradicate minimal residual disease following standard-therapy in Project 1. Patients receiving novel NK or PR1-CTL cellular therapies post-SCT in Project 2 will also be monitored to determine the persistence of anti-CML immunity resulting from these therapies. Because the Project 2 studies occur in the context of immunosuppression post-transplant, and because these therapies may lead unexpected effects on normal immune homeostasis, we will assess overall Immune status in addition to monitoring NK- or PRI-CTL-mediated anti-CML immunitv.

RELEVANCE (See instructions): This GMP-IA Core will provide novel, cutting edge cellular therapies to high-risk CML patients who have a poor prognosis with standard therapy. These cellular therapies have the potential to make fundamental improvements in the treatment of CML. This core will assess anti-CML immunity and general immune system health to advance the understanding of mechanisms of these new treatments and to optimize treatments for overall patient benefit