Exploring the State of the Science in the Field of Regenerative Medicine Challenges of and Opportunities for Cellular Therapies: Proceedings of a Workshop (2017) / Chapter Skim
Currently Skimming:
3 Hematologic and Immunologic Applications
3 Hematologic and Immunologic Applications
Pages 19-32
The Chapter Skim interface presents what we've algorithmically identified as the most significant single chunk of text within every page in the chapter.
Select key terms on the right to highlight them within pages of the chapter.
From page 19... ...
(Urnov) • Hematopoietic stem cell transplant is a well-established treatment for a number of conditions.
|
From page 20... ...
, using modified cells and gene therapy to improve clinical outcomes for patients who undergo hematopoietic stem cell transplantation (HSCT) , and the use of engineered T cells for the effective treatment of cancer.
|
From page 21... ...
. This finding, in combination with evidence from the "Berlin patient," an individual cured of HIV-1 infection after receiving an allogeneic transplant with stem cells carrying nonfunctional CCR5, spurred researchers at Sangamo BioSciences to develop CCR5-targeted HIV treatments (Tebas et al., 2014; Zou et al., 2013)
|
From page 22... ...
ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION Allogeneic HSCT, or bone marrow transplantation, has been well established for nearly 30 years as a standard-of-care treatment for many monogenic diseases and cancers, said Harry Malech, chief of the Laboratory of Host Defenses and chief of the Genetic Immunotherapy Section at the National Institute of Allergy and Infectious Diseases. It has become the standard of care for hemoglobinopathies, inherited bone marrow failure syndromes, primary immune deficiencies, lysosomal storage diseases, and some metabolic enzyme deficiencies and leukodystrophies.
|
From page 23... ...
Prevention, detection, and effective treatment of viral, bacterial, and fungal infections that may occur due to the immunodeficient status of transplant patients Increasing the Pool of Suitable Donors Often, the best donor is an HLA-matched sibling, Malech said; however, the availability of matches through unrelated donors has vastly increased in recent years due to the National Marrow Donor Program, and the best donor is increasingly likely to be found through that program.2 One challenge that still remains is that individuals of mixed ethnic heritage may have trouble finding a donor within the National Marrow Donor Program, Malech said. To expand the potential donor pool, researchers have also been exploring the possibility of performing haploidentical HSCT using a relative who is a partial HLA match (Locatelli et al., 2013)
|
From page 24... ...
. Targeted HSPC conditioning regimens that use only biologic agents represent a disruptive innovation that could transform HSPC transplantation, Malech said.
|
From page 25... ...
Advances in Gene Therapy The first evidence of clinically beneficial gene therapy for monogenic immune deficiencies was observed using infusions of murine gamma retrovirus vector-transduced autologous HSCs to treat X-linked severe combined immune deficiency (X-linked SCID) or adenosine deaminase-deficient severe combined immune deficiency (Aiuti et al., 2009; Gaspar et al., 2011; Hacein-Bey-Abina et al., 2010, 2014)
|
From page 26... ...
. At the conclusion of his presentation, Malech briefly reported that several recent trials of lentivector gene therapy have demonstrated promise for significant long-lasting clinical benefits for patients with monogenic illnesses including thalassemia (CavazzanaCalvo et al., 2010)
|
From page 27... ...
These early findings resulted in Science naming cancer immunotherapy 2013's Breakthrough of the Year, highlighting the work on CAR therapy and another approach called checkpoint blockade, which is aimed at blocking inhibitors of the immune response.
|
From page 28... ...
Innovations in cell-manufacturing sciences to get the product to patients more efficiently 4. Integration of gene transfer and gene editing technology with CAR therapy The Future of CAR T Cell Therapies T cells have been used as medicines for a number of years; however, progress in adoptive T cell therapy has been slow because of a lack of antigen-specific human T cells (Themeli et al., 2013)
|
From page 29... ...
Both patients and providers were reluctant to participate in early CAR T cell therapies, Sadelain said, and moving forward would not have been possible without addressing concerns and educating people about how the therapy worked. PATIENTS AS ACTIVE PARTICIPANTS IN HUMANITY-BASED RESEARCH Research participants are often viewed simply as "study subjects," but Jennifer Fields, a patient advocate, argued that they should be considered "active participants of humanity-based research." Having an informed patient population is critical to supporting continuing research in the field, she said, but there is a significant communications gap in the current scientific research process.
|
From page 30... ...
Controlling the risks of these therapies is an iterative process that requires investigators, regulators, and clinical physicians to work together closely to quickly address effects as they are identified, Malech said. Sadelain noted that, in addition to the failure of mouse models to predict cancer as an effect of gene therapy, mouse models also failed to predict heart failure as a result of CAR T cell therapy.
|
From page 31... ...
Dunbar suggested that liaisons who are informed about the science and about the realities of clinical trials could act as brokers between researchers and patients to present a more balanced view.
|
Key Terms
This material may be derived from roughly machine-read images, and so is provided only to facilitate research.
More
information on Chapter Skim is available.