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C H A P T E R 94

OVERVIEW AND HISTORICAL PERSPECTIVE OF

CURRENT CELL-BASED THERAPIES

Leslie E. Silberstein and Helen E. Heslop

The discovery in 1900 by Karl Landsteiner of the ABO blood group involving hematopoietic/bone marrow-derived cells has evolved,
system paved the way for transfusion therapy, that is, the ability to similar to blood banking and transfusion medicine, into a highly
safely infuse living blood cells as a therapeutic modality (see Chapters regulated discipline with oversight by several regulatory agencies,
95–109). Thus, the discipline began with the collection by venipunc- including the FDA and the National Institutes of Health Recombi-
ture of whole blood, which required anticoagulation and storage at nant DNA Advisory Board (see Chapters 96 and 97).
refrigerated temperatures. These procedures were optimized when it
became possible to isolate different cell populations, such as red blood
cells, platelets, and granulocytes. The term blood banking refers to TABLE Evaluation of Allogeneic Donor for Eligibility to
collection and storage of blood products, both of which are highly 94.1 Provide Cell Therapy Product
regulated by the United States Food and Drug Administration (FDA). Evaluation/Test a Rationale/Purpose
The pioneering work by E. Donnall Thomas and others between
1950 and 1970, demonstrating the feasibility of transfusing bone Complete history and physical To review the donor’s medical and
marrow cells (i.e., bone marrow transplantation) as a treatment social history for risk factors for
modality marked the next significant development of cellular thera- communicable disease agents and
1
pies (see Chapters 103–109). The success of bone marrow engraft- diseases.
ment is related to the presence of hematopoietic stem and progenitor To review for clinical evidence of risk
cells in the bone marrow; immune cells in the graft, including T cells factors or diseases.
and natural killer cells, mediate graft-versus-tumor effects in patients Donor questionnaire To evaluate risk factors for
transplanted for hematologic malignancy. Hematopoietic stem cell communicable disease (using
populations, currently used for therapy of malignant and nonmalig- uniform donor questionnaire
b
nant disease, can be isolated from bone marrow, from (mobilized) drafted by an international task
peripheral blood, and from umbilical cord blood (see Chapter 95). force).
An exciting new development in hematopoietic stem cell transplanta- CBC, platelets, differential To evaluate for evidence of
tion is the genetic manipulation/transduction of the hematopoietic hematologic abnormalities.
stem cell to correct hereditary disorders such as the congenital
2,3
immunodeficiencies and hemoglobinopathies (see Chapter 98). Electrolytes, BUN, creatinine, To evaluate for evidence of liver or
More recently, the ability to isolate and expand cell populations in glucose, total protein, electrolyte abnormalities.
culture has led to the evaluation of a number of cell therapy strategies. albumin, total bilirubin,
Only one approach, a dendritic cell vaccine, has so far been approved alkaline phosphatase, ALT,
4
by the FDA in the United States, but several CD19 CAR products AST, LDH
have obtained breakthrough designation and will likely be approved ABO typing To confirm identity.
5
soon. Infusions of other cells expanded ex vivo or significantly HLA typing To conduct HLA matching for some
manipulated are conducted as experimental procedures through the indications.
FDA’s Investigational New Drug application process. Many such To confirm identity.
studies use autologous cells, which do not have a risk for transferring
communicable disease, but (because they are patient-specific prod- HIV-1 antibody, HIV-2 antibody, To exclude communicable disease
ucts) make late-stage clinical trials more challenging. The use of HIV NAT, HTLV-1/2 agents.
allogeneic cells requires careful assessment of donor eligibility because antibodies, HBs antigen, Must be collected at the time of
of the risk for infectious disease transmission or transfer of immune HBc antibody, HCV NAT, recovery of the cells or tissue from
6
reactivity (Table 94.1). Allogeneic cells may also be used to produce CMV antibody, serologic test the donor; or up to 7 days before
a patient-specific product in some clinical settings, such as treatment for syphilis, West Nile virus or after recovery.
of relapse postallogeneic transplant in which full HLA matching is NAT, Chagas disease (if For donors of peripheral blood stem/
required. In other applications, however, third-party cells may have indicated by region) progenitor cells, oocytes and bone
benefits, including the advantage of broad applicability since a larger marrow may be collected for
number of patients can receive a product generated from a single testing up to 30 days.
donor. a The donor eligibility rule requires human cell and tissue products
A broad range of cell types are currently being evaluated in clinical establishments to screen and test cell and tissue donors for risk factors for, and
trials (see Chapters 97–101). Immune cell populations with distinct clinical evidence of, relevant communicable disease agents or diseases.
Additional Investigational New Drug-specific tests may also be mandated. All
biologic properties are being infused to treat cancer and infectious facilities need to use United States Food and Drug Administration-approved
diseases, and some approaches have progressed to late-phase testing testing.
b
Foundation for the Accreditation of Cellular Therapy (FACT) Standards: HPC
(see Chapters 100 and 101). Nonhematopoietic stromal cells from Donor History Questionnaire http://www.factwebsite.org/Inner.aspx?id=163
bone marrow have attracted considerable interest recently for use in ALT, Alanine aminotransferase; AST; aspartate aminotransferase; BUN,
tissue repair and immunomodulation, largely because of their multi- blood urea nitrogen; CBC, complete blood cell count; CMV, cytomegalovirus;
lineage differentiation potential and their secretion of cytokines and HBc, hemoglobin C; HBs, hemoglobin S; HCV, hepatitis C virus; HIV, human
chemokines (see Chapter 99). Their use, while experimental, is immunodeficiency virus; HLA, human leukocyte antigen; HTLV-1/2, human
T-lymphotropic virus-1/2; LDH, lactate dehydrogenase; NAT, nucleic acid testing.
promising. Thus, significant experience in cell-based therapies
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