THE FRED HUTCHINSON CANCER RESEARCH CENTER 
AND THE UNIVERSITY OF WASHINGTON SCHOOL OF MEDICINE 
DEPARTMENT OF MEDICINE, DIVISION OF ONCOLOGY 
10/07/9F\ 
1. Phase I Study of Cellular Adoptive Immunotherapy Using Genetically Modified CD8 + HIV-Specific T 
cells for HIV Seropositive Patients Undergoing Allogeneic Bone Marrow Transplant 
Investigators: S.R. Riddell, M.D., Assistant Member, FHCRC, 667-5249; P.D. Greenberg, M.D., Professor 
of Medicine and Immunology UW, Member FHCRC; R.W. Overell, Ph.D., Immunex Corporation; T.P. 
Loughran, M.D., Associate Member FHCRC; M.J. Gilbert, M.D., Senior Fellow, FHCRC; S.D. Lupton, 
Ph.D., Immunex Corporation; J. Agosti, M.D., Immunex Corporation; S. Scheeler, Immunex Corporation 
R.W. Coombs, M.D., Assistant Professor of Medicine, UW; L. Corey, M.D., Professor of Medicine, UW. 
Emergency 24-hour Phone: 667-5001 
2. Introduction 
This clinical protocol proposes to examine the safety and potential antiviral efficacy of transferring 
genetically modified HIV-specific CD8 + cytotoxic T lymphocytes (T c ) as additional antiviral therapy with 
AZT to HTV seropositive patients undergoing allogeneic bone marrow transplant for malignant lymphoma. 
The CD8 + T c clones will be modified by retrovirus mediated gene transfer to contain a marker/suicide gene, 
which will facilitate analysis of the in vivo persistence of transferred T cells and provide a potential means of 
ablating T cells if toxicity occurs. 
3. Background and Rationale 
Infection with human immunodeficiency virus (HIV) produces a cellular immunodeficiency eventually 
resulting in AIDS [1,2]. Approximately one to two million people in the United States are believed to be 
infected with HIV, and it is estimated that between 25 and 65 percent of infected individuals will develop 
AIDS within seven years of primary infection [3,4]. The development of clinical AIDS carries a dismal 
prognosis with a median survival of twelve to twenty-four months following diagnosis without antiretroviral 
therapy [5,6], 
Therapeutic efforts for patients with AIDS have centered on improved treatment of opportunistic 
infections and the use of antiretroviral drugs targeting the viral reverse transcriptase to limit HIV spread. 
Studies evaluating the efficacy of the antiviral agent azidothymidine (AZT) for patients with clinical AIDS or 
the prodromic findings denoted as the AIDS-related complex (ARC) have demonstrated a modestly improved 
survival, but treatment related hematopoietic toxicity, the in vivo selection of AZT resistant HIV variants and 
the development of B cell lymphomas have emerged as significant obstacles [7-10]. The B cell lymphomas 
developing in HIV seropositive individuals may arise in part due to the cellular immunodeficiency caused by 
HIV infection [10-12], These lymphomas often respond to chemotherapy, but the overall prognosis is poor 
with a median survival of less than one year. Allogeneic BMT is a potentially curative modality for non-HIV 
infected individuals with B cell lymphoma [13] and may be of potential benefit for lymphoma patients 
harboring HIV [14]. Moreover, it is conceptually possible that BMT could provide immunologic 
reconstitution if host HIV infection could be prevented from spreading to donor derived hematopoietic cells, 
thus potentially preventing or delaying the onset of AIDS. 
A. Bone Marrow Transplantation for HIV Seropositive Individuals 
Bone marrow transplant in the context of host HIV infection is based on the hypothesis that 
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