The (Connell and O'Reilly Families) Cell Manipulation Core Facility (CMCF), at Dana-Farber Cancer Institute (DFCI) was created in 1996 to be a manufacturing facility for production of safe and effective novel cellular component therapies, that meet regulatory guidelines for clinical use and enable cellular therapies to be translated from the bench to bedside. The goal of this facility is to assist DF/HCC investigators and sponsors in developing new cell-based therapies for cancer, gene therapy products for genetic diseases, and adoptive immunotherapy products. Many of these cellular products are manufactured in the context of clinical research studies designed to evaluate the toxicity and efficacy of novel treatments.
The CMCF facility, located in the Jimmy fund building, is dedicated to the production of clinical-grade cellular therapy products for patients who participate in clinical trials conducted by DF/HCC investigators. All procedures are performed in environmentally-controlled conditions according to current Good Manufacturing Practices (cGMP) established for cell and tissue processing. The third floor accommodates all of the production clean room areas while space on the ground floor is devoted to the storage of cellular products, tissues, and blood and tumor samples in liquid nitrogen and mechanical freezers. In addition, the Pasquarello Tissue Repository, located on the 6th floor, collects and stores patient samples solely for research use.
The CMCF is available to both clinical and laboratory investigators at all DF/HCC institutions and will provide services to patients at all DF/HCC affiliated hospitals. The staff of the CMCF are committed to working with DF/HCC investigators at all levels of clinical trial development and execution. In addition to manufacture of clinical grade cellular therapy products, CMCF services include pre-clinical development of manufacturing procedures, facilitation of DF/HCC and FDA review, data management, in-process and release testing of products, quality control monitoring, coordination of internal and external audits, and generation of reports for publication. The CMCF has been accredited by the Foundation for the Accreditation of Cellular Therapy (FACT), and is licensed by CLIA to perform high-complexity testing. The CMCF supports the Cancer Vaccine Center at DFCI, the Center for Human Cell Therapy at Boston Children’s Hospital and is also a member of the Joint Program in Transfusion Medicine.
Leadership and Staff
Director: Jerome Ritz, MD
Assistant Medical Director / Clinical Instructor: Sarah Nikiforow MD, PhD
Administrative Director: Olive Sturtevant, BA, MT (ASCP) , SBB, SLS, MHP
Technical Director - Stem Cell Therapies Lab: Darlys Schott, BS, MT (ASCP), SBB
Technical Director - Novel Cellular Therapies Lab: Hélène Negre, PharmD, PhD
Quality Assurance Manager: Mary Ann Kelley, BS, MT (ASCP)
Associate Business Director: Elaine Zive BS, MBA
Systems Manager: Philip Brzezinski, BS, MBA
Systems Manager: Josh Geary, BA
Supervisor, Novel Cellular Therapies Lab: Heather Daley, BS
Supervisor, Stem Cell Therapies Lab: Karl Stasko, BS, MPH
Supervisor, Quality Control Lab: Renee Manduke, BS
Supervisor, Pasquarello Tissue Lab: Doreen Hearsey, BS
Program Administrator: Gerry MacDonald
Certificates/Registration of Accreditation
The Joint Commission Accreditation Letter
FACT Accreditation Certificate
CMS & CLIA Accreditation Certificate
"The CliniMACS system in combination with a CliniMACS Tubing Set and CliniMACS CD34 Reagent is being investigated for use in selecting and enriching human CD34 positive hematopoietic progenitor cells from leukapheresis products.
The CD34 antigen is a cell membrane glycoprotein expressed by early hematopoietic progenitor cells. Investigative studies with the CliniMACS device have suggested that when re-infused after myeloablative chemotherapy, CD34 positive peripheral blood progenitor cells have been shown to reconstitute all lineages.
The CliniMACS system in combination with the CliniMACS Tubing Set and CliniMACS CD34 Reagent is expected to work in following manner. It takes advantage of the selectivity of monoclonal CD34 antibodies conjugated to magnetic particles. The CD34 positive target cells are selected in an automated separation system.
For labeling of the CD34 positive cells, the leukapheresis product is incubated with the CliniMACS CD34 Reagent. After washing away the excess unbound Reagent the automated selection is started. The CliniMACS system passes the antibody-labeled suspension through a column in which strong magnetic gradients are generated. The column retains the magnetically labeled CD34 positive cells, while unwanted cells flow through and are collected in the negative fraction bag.The system performs several washing steps disposing of most of the liquid into the buffer waste bag. The selected CD34 positive cells are released from the column by removing the column from the magnetic field and eluting the cells into the cell collection bag."
"Protocols in this area involve the isolation, expansion, and ex vivo modification of defined lymphoid populations for infusion to boost specific immunity."
"Dendritic cells are generated from cultured monocytes with cytokines. They are further genetically modified to encode tumor antigens, pulsed with tumor-associated peptides or tumor cell lysate, or combined with adoptive immunotherapy to enhance tumor rejection."
"The CMCF processes HPC components requiring no manipulation, minimal manipulation and also more extensive processing including the purging of tumor cells from autologous HPC, the positive selection of CD34+ progenitor cells or depletion of subset of lymphocytes using the Isolex 300i or the Miltenyi Clinimac systems."
Preparation of Investigational New Drug (IND) Application.
"The generation of tumor vaccines involves the production of autologous tumor cells genetically modified to secrete immune-stimulating cytokines such as GM-CSF to enhance tumor immunogenicity."