IN THE NEWS
Phase II/III Cellular Therapy Trial Hits Primary Endpoint
Administration of StemEx to patients with hematological malignancies who received myeloablative therapy but could not find a related matched bone marrow donor had improved overall survival at 100 days. The StemEx product is an expanded population of stem cells derived from part of a single unit of umbilical cord blood and transplanted along with the remaining, non-manipulated cells from the same unit. The cord blood-derived cellular therapy improved survival in 101 patients compared to historical controls, according to a press release from Gamida Cell.
ALS Patient Begins Cellular Therapy in Phase IIa Clinical Trial
A press release distributed by BrainStorm Cell Therapeutics noted that the first patient has begun treatment with an autologous cellular therapy product in a phase IIa clinical trial to treat Amyotrophic Lateral Sclerosis, also known as Lou Gehrig's disease. Following on positive safety results from a phase I/II trial, patients will receive injections into the muscles and spinal cord of bone marrow cells that have been differentiated to the neural lineage.
The Use of Natural Killer Cells to Treat Cancer Takes Another Step Forward
Five articles published this month in "Transfusion" highlight a milestone in the development of natural killer, or NK, cells as a promising cellular therapy. NK cells transferred from a mis-matched donor may be a powerful tool in the fight against cancer but must be processed appropriately and used fresh. An article by S.A. Koepsell, D.M. Kadidlo et al. describes the testing of an NK cell processing and shipping procedure, and H. Klingemann et al. report the early results of a clinical trial employing that procedure. An article by R. Skeate et al. describes complications from improperly processed cells, while articles by S.A. Koepsell, J.S. Miller et al. and Shook et al. provide reviews of NK cell manufacturing and testing. Marie Csete, MD, PhD, provides an editorial about these important developments in this issue. The journal "Transfusion," included the Klingemann et al. article in its continuing medical education program.
Cellular Therapy for Knee Repair
A stem cell product, Cartistem, is undergoing testing in a clinical trial for the repair of knee cartilage caused by aging, trauma and degenerative diseases. This allogeneic cell product, derived from umbilical cord blood, will be tested in combination with microfracture surgery, a commonly used surgical technique. The trial, conducted at Rush University Medical Center, will evaluate the safety of the treatment and the regeneration of cartilage.
Biotime Set to Purchase Embryonic Stem Cell Assets from Geron
Intellectual property, patents, and an ongoing clinical trial of an embryonic stem cell-derived cellular therapy for spinal cord injury will be purchased from Geron by BioTime, Inc. Geron, known for launching the first clinical trial of a cellular therapy derived from embryonic stem cells, earlier announced its decision to focus on experimental therapies for cancer, leaving the fate of its embryonic stem cell therapy program uncertain.
Allogeneic Stem Cell Trial for Spinal Cord Injury
In a phase I safety trial, an allogeneic stem cell product derived from a human spinal cord will be injected into the injury site of thoracic spinal cord injury patients with complete paralysis. This trial follows preclinical evidence that the cellular therapy product could engraft and form neurons in paralyzed rats, helping those animals regain locomotor function.
Second Cohort of Patients Enrolled in Clinical Trial of Stem Therapy for Stroke
SanBio, Inc., will test the safety and efficacy of its allogeneic cellular therapy product derived from bone marrow in a second cohort of patients suffering from stroke injuries. In this trial, which is being conducted at Stanford University, Northwestern University, and the University of Pittsburgh, the cellular therapy product will be injected into the brain adjacent to the area damaged by ischemic stroke. No safety issues were reported from the first cohort of patients.
Mesoblast to Begin Phase II Clinical Trial of Cellular Therapy for Rheumatoid Arthritis
Allogeneic mesenchymal precursor cells harvested from bone marrow will be injected intravenously into rheumatoid arthritis patients who have had incomplete or inadequate response to a biologic therapy. The randomized, double-blind placebo-controlled trial of 48 patients will assess both safety and effectiveness.
Cellular Therapy Derived From Embryonic Stem Cells for Macular Degeneration Engrafts in Eyes of Patients
In an interim report of its trials for Stargardt's macular dystrophy and dry age-related macular degeneration, Advanced Cell Technology revealed that the human embryonic stem cell-derived cells had engrafted in patients, coinciding with gains in visual acuity in some patients. The company believes that the cells, injected into the sub-retinal space, must engraft and replace parts of the damaged retinal pigmented epithelium to be effective.
Hepatocytes for Cellular Therapy: A Puzzle Waiting to Be Solved
An effective cell therapy for many incurable liver conditions has been tantalizingly close for years: animal models of liver disease have been cured using cellular therapies; intriguing case reports describe patients who benefitted from cellular therapy treatments; and at least a dozen cellular therapy clinical trial results have been published. However, these promising studies and limited clinical successes have yet to be integrated into widely-applicable and durable interventions. This article explores state-of-the-art hepatocyte therapy and highlights both the current challenges and future potential faced by researchers in this field. Read more
Fat-Derived Stem Cells: Why Didn't I Think of That?
The idea of using subcutaneous fat as a source of cells for cellular therapy applications is appealing. The harvest procedure is relatively less invasive than surgical procedures necessary to derive cells from deeper anatomic sites, and people appear to be more than willing to shed a few excess adipocytes. Relocation of fat from the waist or hips to a site in the body deficient in fat cells to repair soft tissue damaged by disease, trauma, or lost with age seems like a good idea. Clinical experience, however, has revealed deficiencies in this strategy. This article analyzes recent advances in the field of adipocyte cell therapy that may make this procedure more effective than previously reported. The article also explores the potential of adipose derived cells for other therapeutic indications. Read more
REGULATORY AND GOVERNMENT UPDATE
AABB Task Force Updates HPC, Apheresis and HPC, Marrow Donor History Questionnaire
The HPC, Apheresis and HPC, Marrow Donor History Questionnaire Version 1.3 materials are now available online. The AABB Interorganizational DHQ-HPC Task Force updated the materials to incorporate additional recommendations based on clinical evidence — namely those regarding a history of positive test results — from section IV.F of the Food and Drug Administration's "Guidance for Industry: Eligibility Determination for Donors of Human Cells, Tissues, and Cellular and Tissue-Based Products," August 2007. Other changes were made to provide clarity, specificity and consistency and to harmonize the DHQ materials with the National Marrow Donor Program. A complete summary of the updates is available online.
The HPC, Apheresis and HPC, Marrow DHQ materials were developed to provide establishments with a standardized tool to screen allogeneic hematopoietic progenitor cell donors for communicable disease risk factors. Version 1.2 materials will remain available until July 2013 to facilitate the transition.
Advisory Group Seeks Comment on Draft Terminology for CT Labeling
The Cellular Therapy Coding and Labeling Advisory Group, or CTCLAG, has proposed draft terminology to address the concern that a number of products with the "TC," or Therapeutic Cell, designation do not have obvious therapeutic benefit. The CTCLAG proposal intends to accommodate current users by minimizing the amount of change and aligning the terminology with fields such as tissue banking that use ISBT 128 terminology. The deadline to submit comments on the proposal is March 15, 2013.
Improved Characterization of Bone Marrow Stromal Stem Cells Could Support Use as Safe Therapies
A team of researchers at the Office of Cellular, Tissue and Gene Therapies of the FDA's Center for Biologics Evaluation and Research has used a mass spectrometry-based proteomics technique to characterize human bone marrow multipotent stromal cells, or hBM-MSC. The technique may result in safer and more effective therapies. In their study, the scientists focused on the analysis of proteins on the surface of hBM-MSC that had been multiplied in a culture dish but had not yet differentiated or matured. The team identified twice as many membrane proteins than had been reported previously, including 14 new markers that may be used to characterize hBM-MSC. These specific cells hold potential for cellular therapies because, in addition to their role in preventing cell death and supporting immune system functions, they are thought to play key roles in repairing or regenerating organs and helping the body grow new blood vessels. The research was published in the "Journal of Proteomics." More information is available online.
FDA Issues Rule on Current Good Manufacturing Practice Requirements for Combination Products
The FDA has issued a final rule on the application of current good manufacturing practice, or CGMP, requirements applicable to combination products. The rule, which creates Title 21 of the Code of Federal Regulations Part 4 Subpart A, is intended to clarify which CGMP requirements apply when drugs, devices and biological products are combined. The rule sets forth a transparent and streamlined regulatory framework for firms to use when demonstrating compliance with CGMP requirements for "single-entity" and "co-packaged" combination products. The rule will go into effect on July 22, 2013.
CBER, FDA – HCT/P Inspection Information
The FDA has updated HCT/P inspections information with Fiscal Year 2012 data. The summary includes inspections performed and inspection conclusions since Fiscal Year 2003.
AABB Posts "Ask the FDA and CMS/CLIA" Annual Meeting Session Transcript
The transcript from the "Ask the FDA and CMS/CLIA" session of the AABB's 2012 Annual Meeting & CTTXPO is now available on the association's website. The session featured discussions of the policies, regulations, guidance documents and inspection programs relating to the oversight of blood and cellular therapies activities by the FDA and the Centers for Medicare and Medicaid Services' Clinical Laboratory Improvement Amendments program. Individuals with questions may contact AABB's Regulatory Affairs department.
Pre-existing Cardiomyocytes Responsible for Renewal of Heart Muscle
There is debate in the cardiovascular field over whether new heart cells created to maintain cardiac homeostasis throughout mammalian adult life originate through turnover of existing cardiomyocytes or from cardiac stem cells. Senyo et al. take a novel approach to explore this question by using pulse–chase techniques to measure DNA synthesis in the adult heart. The authors conclude that during normal aging, pre-existing cardiomyocytes are the dominant source of cardiomyocyte replacement in normal myocardial homeostasis — a process that is increased during recovery from myocardial infarction.
Considerations in Early Clinical Trial Design for Orthopedics
The design of early clinical studies in orthopedics presents specific ethical issues that should be addressed. Niemansburg et al. present a review of these issues that includes the importance of matching study design with outcome measures, the assessment of risks and benefits, and appropriate participant selection.
Generation of Induced Pluripotent Stem Cell Lines Reveals Genetic Mosaicism in Fibroblasts
A reason cited that induced pluripotent stem cells, or iPS cells, may not be clinically relevant is that the process of deriving the cells induces genetic transformations that are dangerous to the patient. In contradiction to that argument, Abyzov et al. reported that a large proportion of genetic copy number variations found in iPS cells were present at very low frequency in the fibroblast cell population from which they were derived. These results imply that copy number variation found in iPS cells may not be a result of the iPS reprogramming method, but that clonal selection of iPS cells may identify rare copy number variants in the parental lines. In addition to addressing doubts about clinical fitness, this research suggests that iPS technology could be useful for discovering low-frequency copy number variations in human tissue.
Clinical Outcomes Equivalent Between Patients Who Received Related and Unrelated Peripheral Blood Stem Cells
Donation of peripheral blood stem cells from relatives can be accepted following less strict criteria than from unrelated donors, potentially increasing safety risk. A study conducted at the Leiden University Medical Center, Netherlands, compared outcomes of recipients of stem cells from related donors that would have been deferred if originating from an unrelated source to eligible and unrelated donors. Both patient populations reported few post-treatment adverse events.
EVENTS, OPPORTUNITIES, RESOURCES
AABB Center for Cellular Therapies to Develop Directory of Training Opportunities
The AABB Center for Cellular Therapies is seeking contributions to develop a directory of training opportunities. Upon completion, the directory will offer an extensive list of education programs related to cellular therapy laboratory practice, quality activities, patient care and clinical programs. All organizations offering such opportunities are encouraged to complete the online submission form. AABB will post all relevant submissions. Preference will be given to AABB-accredited facilities.
PACT Workshop on Developing Cellular Therapies to Be Held in April
Production Assistance for Cellular Therapies, or PACT, will be conducting a workshop on April 9, 2013, titled "Developing Cellular Therapies: From Preclinical Safety to Clinical Evaluation." Topics covered include the transition of cellular therapies to the clinic, development of in vivo models, and novel cellular therapies. The workshop will be held at the University of Wisconsin-Madison, and is free of charge and open to the cellular therapy community.
FOR MEMBERS ONLY
"Novel Therapies Showcase" Added to AABB CCT Subsection Activity
The Novel Therapies and CT Product Development subsection, led by Pampee Young, MD, PhD, and Magali Fontaine, MD, PhD, has recently introduced the "Novel Therapies Showcase." This showcase features novel therapies in development by fellow members and invited guests. As part of this feature, Vic Lemas, PhD, and Janice Davis Sproul, MAS, MT(ASCP), of Johns Hopkins University, recently discussed the role they played in the double-arm transplant of an Iraqi veteran. During this presentation, they delivered a comprehensive description of their experience preparing bone marrow extractions for infusion. The purpose of the treatment is to achieve graft tolerance by creating mixed chimerism of the bone marrow. All members interested in novel therapies and CT product development are encouraged to enroll in this subsection.
Join the Cellular Therapy Group Within the AABB Community
One of the benefits of AABB individual membership is access to the association's online Community. This Web-based discussion platform is designed to help members network and connect with colleagues and other professionals, share collective knowledge, and post technical questions relevant to cellular therapies that are answered by peers. New members and members who have not yet discovered this feature are encouraged to log in to the AABB Community website, select "Cellular Therapy" and click "Join This Group." Sign up to receive email alerts of new postings by clicking on the golden alarm bell that is visible in the "Discussions" section.
AABB CCT Business Management Subsection Renamed "CT Management"
The AABB Center for Cellular Therapies business management subsection has been renamed CT Management. The new name better represents the focus of the subsection on financial and management issues that affect efficiency and productivity of cellular therapy facilities. Interested members are encouraged to join.