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Cell Manipulation Core

October 3, 2013 | eNews

The mission of the Cell Manipulation Core Facility (CMCF) is to produce safe and effective cellular components for patients with cancer that are enrolled in novel therapeutic clinical research protocols. The CMCF supports primarily translational research and works closely with many laboratory investigators in the DF/HCC Cancer Immunology Program and clinical investigators in other disease-based programs within DF/HCC. CMCF investigators work in diverse areas including hematopoietic stem cell transplantation, cancer vaccines, and adoptive cellular therapy of cancer.

The CMCF has begun working with blood management company, Haemonetics Software Solutions, to implement an Edgecell software platform. Once implemented, this manufacturing software system will allow the laboratory to electronically document critical stages of manufacturing of cellular products, track supplies used in manufacturing, perform calculations, and track a product from collection all the way to infusion. This will allow for critical data from cellular processing to be easily documented in a database for efficient retrieval and data analysis.

The CMCF continues to be one of five national Production Assistance for Cellular Therapy (PACT) centers. The CMCF is able to assist investigators in the development of new cellular therapies for non-cancer applications. All preclinical work and development of new cell manufacturing procedures supported by PACT will take place in a closely affiliated laboratory located at Boston Children’s Hospital. Once these procedures are finalized, the CMCF is responsible for validating the manufacturing SOPs and will manufacture these products for subjects enrolled on clinical trials at various institutions throughout the United States.

All procedures in the CMCF are performed according to current Good Manufacturing Practices (cGMPs) for cell and tissue processing. The policies and procedures established in the facility comply with federal standards and regulations, ensuring the production of safe, effective components for clinical use. Cellular products processed by the CMCF are provided in the context of clinical research protocols that have been reviewed and approved by the DF/HCC Scientific Review Committee and Human Subjects Protection Committee. Together with adherence to cGMPs, the requirement that extensive cell processing is only provided for patients enrolled on approved clinical research protocols ensures that this core facility provides a unique service to DF/HCC programs and investigators.

In 2012, the CMCF received re-accreditation from the Foundation for the Accreditation of Cellular Therapy (FACT) and became the first center to receive accreditation under new FACT standards for extensive cellular manipulation. The CMCF has continued to support a variety of innovative clinical research protocols carried out in patients with solid tumors as well as hematologic malignancies. Several new protocols have been initiated through CMCF in the past year:

A multi-center, Phase III, randomized trial of reduced intensity conditioning (RIC) and transplantation of double unrelated umbilical cord blood (dUCB) versus HLA-haploidentical related bone marrow (haplo-BM) for patients with hematologic malignancies

Principal Investigator: Corey Cutler, MD (DFCI)

Description of Protocol: Although the majority of patients who require allogeneic stem cell transplantation are able to identify an HLA-matched donor, a fully matched related or unrelated donor cannot be identified for a substantial fraction of patients. Previous single institution Phase II studies have documented excellent clinical outcomes using either partially mismatched umbilical cord stem cells or haplomismatched related donor stem cells for these patients. This clinical trial represents a multi-center randomized comparison of the two best approaches to determine the best stem cell source for these patients. The CMCF processes both types of stem cells for this clinical trial.

A randomized placebo-controlled Phase II trial of irradiated, adenovirus vector transfected GM-CSF secreting autologous leukemia cell vaccination (GVAX) versus placebo vaccination in patients with advanced MDS/AML after allogeneic hematopoietic stem cell transplantation

Principal Investigator: Vincent Ho, MD (DFCI)

Description of Protocol: Previous Phase I studies carried out in the Cancer Immunology Program have suggested that administration of autologous leukemia vaccines genetically engineered to secrete GM-CSF early after allogeneic stem cell transplantation results in the generation of effective anti-leukemia immunity and reduces the incidence of relapse after stem cell transplantation. This large randomized Phase II trial will provide a more definitive assessment of potential clinical efficacy and concomitant immunologic studies will carefully examine the immunologic effects of vaccination in the early post-transplant period. The CMCF processes all of the allogeneic stem cell products and also manufactures all of the autologous tumor cell vaccines for patients enrolled on this clinical trial.

A Phase I trial of a tendritic cell activating scaffold incorporating autologous melanoma cell lysate (WDVAX) in metastatic melanoma patients

Principal Investigator: Stephen Hodi, MD (DFCI)

Description of Protocol: Investigators in the Cancer Immunology Program have collaborated with engineers at the Wyss Institute for Biologically Inspired Engineering at Harvard to create a “scaffold tumor vaccine.” This scaffold incorporates an autologous tumor cell lysate into a highly controlled immunogenic environment that also includes GM-CSF and CpG oligonucleotides. Porous scaffolds created individually for each patient are manufactured in the CMCF and subsequently surgically implanted in subcutaneous tissue.

A Phase II, controlled trial, of a single ProHema-CB unit (ex vivo CXCR4-Upregulated CD34+ hematopoietic progenitor cells, cord blood) as part of a double umbilical cord blood transplant following myeloablative conditioning for patients age 15-55 years with hematologic malignancies

Principal Investigator: Corey Cutler, MD (DFCI)

Description of Protocol: Previous studies in the Leukemia Program demonstrated the in vitro stimulation of hematopoietic progenitor cells with prostaglandin resulted in enhance engraftment in both zebrafish and murine models. The safety and potential efficacy of this approach was tested in a Phase I clinical trial of double umbilical cord stem cell transplantation at DF/HCC. This new multi-center Phase II study will establish the efficacy and safety of this approach in a larger number of patients using in vitro methods that have been optimized to enhance expression of CXCR4 after in vitro stimulation. The CMCF developed the initial manufacturing methods and will perform the in vitro processing of umbilical cord blood stem cells.