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:
CULTIVATED CORNEAL EPITHELIAL CELLS FOR TRANSPLANTATION IN PATIENTS WITH UNILATERAL LIMBAL STEM CELL DEFICIENCY
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Project Title: Cultivated Autologous Limbal Epithelial Cell (CALEC) Transplantation
Principal Investigators: Ula Jurkunas, MD (MEEI), Jerome Ritz, MD (DFCI), Allison Ayala MS (Jaeb)
Co-Investigators: Reza Dana, MD (MEEI), Jia Yin, MD, PhD (MEEI)
Coordinating Centers: Massachusetts Eye and Ear Infirmary, Dana-Farber Cancer Institute and Jaeb Center for Health Research
Description of Project: The NIH-NEI-funded study (NCT02592330) with an FDA-approved IND (#16102) will involve performing a small limbal biopsy from the healthy fellow eye, following which the removed cells will be cultivated to expand the stem cells (CALEC cells). After a 2- to 3-week period, the eye with limbal stem cell deficiency will undergo reconstruction using the CALEC cells. Physicians expect that the risk to the healthy fellow eye will be minimal with this procedure. This open label, randomized study will enroll 24 patients with unilateral limbal stem cell efficiency; 17 will receive CALEC and 7 controls will undergo conjunctival limbal autograft. All patients will be followed for 18 months.
TRANSDUCTION OF HEMATOPOIETIC STEM CELL GRAFTS FOR CLINICAL USE
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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
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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 AcknowledgementIf 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."
CULTIVATED CORNEAL EPITHELIAL CELLS FOR TRANSPLANTATION IN PATIENTS WITH UNILATERAL LIMBAL STEM CELL DEFICIENCY
----------------------------------------------------------------------------------------------------------------------------------
Project Title: Cultivated Autologous Limbal Epithelial Cell (CALEC) Transplantation
Principal Investigators: Ula Jurkunas, MD (MEEI), Jerome Ritz, MD (DFCI), Allison Ayala MS (Jaeb)
Co-Investigators: Reza Dana, MD (MEEI), Jia Yin, MD, PhD (MEEI)
Coordinating Centers: Massachusetts Eye and Ear Infirmary, Dana-Farber Cancer Institute and Jaeb Center for Health Research
Description of Project: The NIH-NEI-funded study (NCT02592330) with an FDA-approved IND (#16102) will involve performing a small limbal biopsy from the healthy fellow eye, following which the removed cells will be cultivated to expand the stem cells (CALEC cells). After a 2- to 3-week period, the eye with limbal stem cell deficiency will undergo reconstruction using the CALEC cells. Physicians expect that the risk to the healthy fellow eye will be minimal with this procedure. This open label, randomized study will enroll 24 patients with unilateral limbal stem cell efficiency; 17 will receive CALEC and 7 controls will undergo conjunctival limbal autograft. All patients will be followed for 18 months.
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 AcknowledgementIf 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."