Cell Manipulation Core

The Connell and O'Reilly Families Cell Manipulation Core Facility (CMCF) assists DF/HCC members in developing new cell-based therapies for patients with cancer who are enrolled in novel therapeutic clinical research protocols, and it supports clinical research studies designed to evaluate the safety and efficacy of these novel treatments.

Key Services

Core services include processing of hematopoietic stem cells for autologous or allogeneic transplantation, generation of tumor vaccines using genetic or culture mediated modification of tumor cells, and preparation of immune cell populations for adoptive cellular therapy. The core also collects and stores follow-up blood and bone marrow samples from subjects treated on protocols that the core produced components for, thus providing an additional service to clinical investigators beyond what cell manufacturing laboratories provide, and ensuring that all research objectives of clinical protocols are met.

Pricing varies; contact the Core for details.

Key services of the Core include:

  • Production of cellular products for patients enrolled on clinical research protocols
    • -Hematopoietic stem cells
    • -Tumor cell vaccines
    • -Dendritic cell vaccines
    • -Adoptive Cellular Therapy Components
  • Cell therapy process development, consultation, and support
    • -Develop manufacturing SOPs
    • -Validate processes and SOPs
    • -Build and activate templates for orders to manufacture, collect, process, and release cellular products to patients (Biotherapy Order Entry, BOE)
  • Clinical trial development consultation for cellular therapeutic studies
    • -Pre-clinical development and trial design
    • -DF/HCC and FDA Review
    • -Data management
    • -Quality control
    • -Internal and external audits
    • -Reports and publications
  • Regulatory (internal and external) consultation and support
    • -Assist with pre-IND FDA meetings
    • -Assist with Chemistry, Manufacturing, and Controls (CMC) section of -IND preparation and patient consents
    • -Assist PI with amendments and annual reports
    • -Assist with IRB protocol submission
    • -Review and sign-off on all protocols
    • -Audit all IND/IDE manufacturing for compliance with IND/IDE and protocol
    • -Prepare for FDA and Sponsor audits
  • Quality control (assays and testing)
  • Quality assurance
    • -Regulatory (FDA) and accreditation (FACT & JC) compliance monitoring
    • -Audit and review procedures, processes, and test results
    • -Assist with labeling requirements
    • -Monitor product non-conformances
  • Cellular product manufacturing, characterization, storage, and distribution
  • Pre- and post-treatment processing and banking of patient samples

Highlighted projects

The CMCF currently supports more than 40 diverse active clinical research protocols, with a focus on translational research in the immune therapy of cancer. Many of these clinical trials and therapies could not have been carried out without the cell manufacturing and regulatory support provided by the Core.

Notable examples of therapies and protocols CMCF currently supports are shown below:

Transduction of hematopoietic stem cell grafts for clinical use

Project Title: Gene transfer for SCID-X1
Principal Investigators:
Sung-Yun Pai, MD (BCH); Luigi Notarangelo, MD; Jerome Ritz, MD (DFCI);
Sponsor:
David A. Williams, MD (BCH)
Coordinating Center:
Boston Children's Hospital
Description of the Project:
A multi-institutional phase I/II clinical trial of somatic gene therapy for patients with SCID-X1 using bone marrow derived CD34+ cells transduced ex-vivo with a novel gibbon ape leukemia (GALV)-virus, pseudotyped gammaretroviral vector encoding the human common cytokine receptor gamma chain ( γc). This clinical trial is performed in collaboration with two other sites in the United States and two sites in Europe. The CMCF is responsible for in vitro processing of patient's bone marrow, which included selection of CD34+ stem cells and transduction with retroviral vector.

Project Title: Gene Therapy for patients with Wiskott Aldrich Syndrome (WAS)
Principal Investigator:
Sung-Yun Pai, MD (BCH)
Sponsor:
David A. Williams, MD (BCH)
Coordinating Center:
Boston Children’s Hospital
Description of the Project:
An open labeled, non-randomized, single center, pilot and feasibility, single arm cohort study involving a single infusion of autologous CD34+ cells transduced with the Lentiviral vector containing the human WAS protein gene (w1.6_hWASP_WPRE (VSVg)) in up to 5 patients with WAS. The CMCF is responsible for in vitro processing of patient's hematopoietic stem cells, which included selection of CD34+ stem cells and transduction with lentiviral vector.

Manufacturing of biochemically engineered implantable tumor vaccines

Project Title: WDVAX melanoma protocol
Principal Investigator:
F. Stephen Hodi, MD (DFCI)
IND Sponsor:
F. Stephen Hodi, MD (DFCI)
Coordinating Center:
Dana-Farber Cancer Institute
Description of Project:
DF/HCC 12-306: FDA BB-IND 15368. A Phase I Trial of a Dendritic Cell Activating Scaffold Vaccine (WDVAX) Incorporating Autologous Melanoma Cell Lysate in Metastatic Melanoma Patients. The CMCF prepares the tumor vaccine, conducts release testing, and manufactures the vaccine delivery scaffold (WDVAX) according to standards provided by the Wyss Institute for Biologically Inspired Engineering at Harvard. Multiple WDVAX scaffolds are prepared for each patient and surgically implanted in subcutaneous tissues at varying intervals. The CMCF also provided regulatory support in preparing the IND application and clinical trial protocol.

Generation of GM-CSF secreting autologous tumor cell vaccines for banking and clinical use

Project Title: GVAX for MDS/AML
Principal Investigator:
Vincent Ho, MD (DFCI)
IND Sponsor:
Robert Soiffer, MD (DFCI)
Coordinating Center:
Dana-Farber Cancer Institute
Description of Project:
DF/HCC 12-217: FDA-BB IND 7248 - 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. This is the first large scale randomized trial evaluating the efficacy of autologous AML GVAX for preventing relapse in high risk patients undergoing allogeneic stem cell transplantation. The CMCF is responsible for processing patient leukemia cells and transfecting them with an adenovirus vector to genetically engineer expression of GM-CSF. This process creates a personalized leukemia vaccine for each patient that is administered several times after transplant.

ADOPTIVE THERAPY WITH HIGHLY PURIFIED REGULATORY T CELLS

Project Title: Donor Treg plus IL-2 for chronic GVHD
Principal Investigator:
John Koreth, MD (DFCI)
Sponsor:
John Koreth, MD (DFCI)
Coordinating Center:
Dana-Farber Cancer Institute
Description of Project:
DF/HCC 13-281: FDA-BB IND 15640 - A Phase I Trial of Regulatory T-cells plus Low-Dose Interleukin-2 for Steroid-Refractory Chronic Graft-versus-Host Disease.  CD4+ regulatory T cells are purified from donor apheresis products using sequential negative and positive selections with monoclonal antibodies conjugated to small iron particles. Highly purified donor regulatory T cells are manufactured in the CMCF and infused in patients with active chronic GVHD. Following cell infusion, patients receive daily injections of low-dose IL-2 for 8 weeks to expand these cells in vivo. The goal of this therapy is to promote immune tolerance in patients with steroid resistant chronic GVHD.


Publication Acknowledgement

If research supported by this core facility results in publication, please acknowledge this support by including the following in your publication(s):
"We thank Dana-Farber/Harvard Cancer Center in Boston, MA, for the use of the Cell Manipulation Core, which provided __________ service. Dana-Farber/Harvard Cancer Center is supported in part by an NCI Cancer Center Support Grant # NIH 5 P30 CA06516."