Core C (Clinical), directed by Dr. Igor Puzanov, MD, will provide integrated oversight, support and coordination for all clinical components of this P01. It will support the implementation and completion of the clinical trials performed within this Program, production and distribution of the cGMP vaccines, immune monitoring of patients and collection of clinical data. Dr. Puzanov will lead Subcore C1 (Regulatory and Clinical Trial Management), being supported by Dr. Edwards (Magee site). He will be assisted by Drs. Kalinski and Chodon, who will be responsible for cGMP production of dendritic cell (DC) vaccines (C2. Dendritic Cell Production) and by Drs. Odunsi, Matsuzaki and Vlad, who will assure effective immune monitoring of the patients on the clinical trials performed within this Program (C3. Immune Monitoring).
The Specific Aims of Core C are:
Aim 1 : Clinical and Regulatory Management. The efforts of Core C1 will focus on a) Assurance that the clinical trials performed within this P01 are approved by the necessary regulatory bodies and that all reporting requirements are met; b) Assurance that the clinical trial will be timely implemented, efficiently completed and properly analyzed; c) Assurance that the correlative and mechanistic studies have access to patient material; and d) fully-integrated development of the follow-up clinical trials, based on the results of all 3 Projects and the results of our other studies held at Roswell Park Cancer Institute (RPCI) and U. Pittsburgh.
Aim 2 : cGMP production of dendritic cell (DC) vaccines. Core C2 will assure: a) Logistic oversight for the collection of patients? tumor and leukapheresis material to the cGMP cell production facility; b) Production of antigen-loaded dendritic cell (DC) vaccines for therapy of patients, in accordance with the clinical protocols and cGMP guidelines; c) Characterization, release and delivery of DC vaccines for the clinical trials; and d) Continued improvement of the process of DC production, testing, preservation, and distribution, to enhance the potency of the cellular products, streamline the process and limit the costs.
Aim 3 : Immune monitoring and cell analyses. Core C3 will provide: a) Procurement, triage and processing of human blood specimens for use in laboratory studies associated with this Program; b) Monitoring patients? systemic (blood) immunologic responses in clinical trials; and c) (Developmental) Identification of the most relevant biomarkers (blood and biomarkers of the individual DC vaccines) predictive of clinical responses. Programmatic Role and Interactions. Core C will support the timely completion of the three clinical trials proposes in years 1-3, coordinated analysis of their (local and clinical) efficacy and potential side effects (with Cores B and D). Based on these data and results of laboratory studies from all three projects, in year 3, Core C will help to finalize the designs of the clinical trials proposed in SA3s of Projects 1 and 2 (combinations with PD-1 blockade), their approval and implementation. In years 3-5, Core C will support the completion of these trials, coordinated analysis of their clinical efficacy and identification of the relevant laboratory correlates.
Core C (Clinical) will provide integrated oversight, and coordination for all clinical components of this P01, supporting the implementation and completion of the clinical trials performed within this P01: production and distribution of cGMP vaccines, immune monitoring of patients and collection of clinical data. In years 1-3, Core C will support timely completion of the three clinical trials proposed in Specific Aims 1 of the three Projects, coordinated analysis of their efficacy (immunologic and clinical) and potential side effects (with Cores B and D). Based on these data and results of laboratory studies performed in SA2s of all projects, in years 3-5 Core C will help finalize the designs of the clinical trials constituting Specific Aims 3 of Project 1 and Project 2 (combinations with PD-1 blockade), their approval, implementation and timely completion, as well as coordinated analysis of their results.
