Immune response to fetal calf serum by two adenosine deaminase-deficient patients after T cell gene therapy.
The first approved clinical gene therapy trial for adenosine deaminase (ADA) deficiency employed autologous T cells grown in fetal calf serum (FCS)-supplemented medium and transduced with a retroviral vector (LASN) also produced in the presence of FCS. Ten years after their enrollment, both patients have circulating T cells containing vector DNA. However, whereas approximately 20% of the circulating T cells from patient 1 are still vector positive, less than 1% of patient 2's T cells have detectable vector. This difference appears to be not only a function of the original transduction efficiency and cell expansion capability in vitro, but also of the immune response that patient 2 developed to FCS components during the course of her treatment. In this study, serum samples from each patient were tested for antibodies to FCS by enzyme-linked immunosorbent assay and anti-FCS responses were demonstrated in both patients. Analysis of immunoglobulin classes revealed comparable levels of IgA and IgM anti-FCS titers. Patient 2, however, had significantly higher IgG responses to FCS than did patient 1. Investigation of the development of anti-FCS responses by IgG subclasses indicated that there was a different pattern in the development of IgG immunity to FCS between the two patients. In addition, significant antibody response to bovine lipoprotein was detected in patient 2, but not in patient 1 or in control samples. These findings suggest that the unique immune response mounted by patient 2 may have influenced the outcome of the gene transfer treatments in this patient.
Tuschong
Laura
L
Clinical Gene Therapy Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892-1820, USA.
Soenen
Sherry L
SL
Blaese
R Michael
RM
Candotti
Fabio
F
Muul
Linda Mesler
LM
D000243:Adenosine Deaminase / Q000172:deficiency; D000818:Animals; D001798:Blood Proteins / Q000276:immunology; D001804:Blood Transfusion, Autologous; D002417:Cattle; D004797:Enzyme-Linked Immunosorbent Assay; D015316:Genetic Therapy; D005822:Genetic Vectors; D006801:Humans; D012190:Retroviridae; D016511:Severe Combined Immunodeficiency / Q000235:genetics / Q000276:immunology* / Q000628:therapy*; D013601:T-Lymphocytes / Q000276:immunology* / Q000637:transplantation / Q000821:virology; D014161:Transduction, Genetic
D001798:Blood Proteins; D000243:Adenosine Deaminase