Page 58 - NIH Guidelines for Research Involving Recombinant or Synthetic Nucleic Acid Molecules (April 2024)
Appendix D-43. Drs. Malcolm Brenner, Robert Krance, Helen E. Heslop, Victor Santana, and James
Ihle, St. Jude Children's Research Hospital, Memphis, Tennessee, may conduct experiments on 35
patients ≥ 1 year and ≤ 21 years of age at the time of initial diagnosis of acute myelogenous leukemia
(AML). The investigators will use the two retroviral vectors, LNL6 and G1Na, to determine the efficacy of
the bone marrow purging techniques: 4-hydroxyperoxicyclophosphamide and interleukin-2 (IL-2)
activation of endogenous cytotoxic effector cells, in preventing relapse from the reinfusion of autologous
bone marrow cells. (Protocol #9303-039)
Appendix D-44. Drs. Helen E. Heslop, Malcolm Brenner, and Cliona Rooney, St Jude Children's
Research Hospital, Memphis, Tennessee, may conduct experiments of 35 patients ≤ 21 years of age who
will be recipients of mismatched-related or phenotypically similar unrelated donor marrow grafts for
leukemia. In this Phase I dose escalation study, spontaneous lymphoblastoid cell lines will be
established that express the same range of Epstein-Barr Virus (EBV) encoded proteins as the recipient.
These EBV-specific cell lines will be transduced with LNL6 or G1Na and readministered at the time of
bone marrow transplant. This study will determine: (1) survival and expansion of these EBV-specific cell
lines in vivo, (2) the ability of these adoptively transferred cells to confer protection against EBV infection,
and (3) appropriate dosage and administration schedules. (Protocol #9303-038)
Appendix D-45. Drs. Robert W. Wilmott and Jeffrey Whitsett, Children's Hospital Medical Center,
Cincinnati, Ohio, and Dr. Bruce Trapnell, Genetic Therapy, Inc., Gaithersburg, Maryland, may conduct
experiments on 15 cystic fibrosis (CF) patients who have mild to moderate disease ≥ 21 years of age.
The replication-deficient type 5 adenovirus vector, Av1CF2, will be administered to the nasal and lobar
bronchial respiratory tract of patients. This study will demonstrate the: (1) expression of normal cystic
fibrosis transmembrane conductance regulator (CFTR) mRNA in vivo, (2) synthesis of CFTR protein, and
(3) correction of epithelial cell cAMP dependent Cl
-
permeability. The pharmacokinetics of CFTR
expression and ability to re-infect the respiratory tract with AvCF2 will be determined. Systemic and local
immunologic consequences of Av1CF2 infection, the time of viral survival, and potential for recombination
or complementation of the virus will be monitored. (Protocol #9303-041)
Appendix D-46. Dr. James M. Wilson of the University of Pennsylvania Medical Center, Philadelphia,
Pennsylvania, may conduct experiments on 20 adult patients with advanced cystic fibrosis lung disease.
An isolated segment of the patients' lung will be transduced with the E1 deleted, replication-incompetent
adenovirus vector, Ad.CΒ-CFTR using a bronchoscope for gene delivery. Ad.CB-CFTR contains the
human gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR) protein.
Pulmonary biopsies will be obtained by bronchoscopy at 4 days, 6 weeks, and 3 months following
treatment. Patients will be monitored for evidence of CFTR gene transfer and expression, immunological
responses to CFTR or adenovirus proteins, and toxicity. (Protocol #9212-035)
Appendix D-47. Dr. Hilliard F. Seigler of Duke University Medical Center, Durham, North Carolina, may
conduct experiments on 20 patients with disseminated malignant melanoma. Autologous tumor cells will
be transduced with a retroviral vector, pHuγ-IFN, that contains the gene encoding human γ-IFN.
Following lethal irradiation, the transduced cells will be readministered to patients for the purpose of
generating cytotoxic T cells that are tumor specific along with the up-regulation of Class I major
histocompatibility antigens. Patients will be monitored for clinical regression of tumors and generation of
tumor-specific cytotoxic T lymphocytes. (Protocol #9306-043)
Appendix D-48. Drs. Stefan Karlsson and Cynthia Dunbar of the National Institutes of Health, Bethesda,
Maryland, and Dr. Donald B. Kohn of the Children’s Hospital of Los Angeles, Los Angeles, California,
may conduct experiments on 10 patients with Gaucher disease. CD34(+) hematopoietic stem cells will be
isolated from bone marrow or from peripheral blood treated with granulocyte-colony stimulating factor.
CD34(+) cells will be transduced with a retrovirus vector, G1Gc, containing cDNA encoding human
glucocerebrosidase and administered intravenously. Patients will be monitored for toxicity and
glucocerebrosidase expression. (Protocol #9306-047)
Appendix D-49. Dr. Gary J. Nabel of the University of Michigan Medical Center, Ann Arbor, Michigan,
may conduct experiments on 12 patients with AIDS to be divided into 4 experimental groups. CD4(+)