A phase 1 study of adoptive transfer of autologous CD8+ T lymphocytes in patients with acquired immunodeficiency syndrome (AIDS)-related complex or AIDS.
Based on preclinical studies showing that CD8+ T lymphocytes of human immunodeficiency syndrome (HIV)-infected subjects have anti-HIV activities, a phase 1 study was undertaken to determine the safety and feasibility of infusing in vitro purified, activated, and expanded CD8+ cells as a therapeutic measure in seven patients with acquired immunodeficiency syndrome (AIDS)-related complex (ARC) or AIDS. Autologous CD8+ cells were first selectively isolated in monoclonal antibody-coated flasks from peripheral blood mononuclear cells recovered by leukapheresis. They were then cultured and expanded with phytohemagglutinin and recombinant interleukin-2 (rIL-2) before infusion. Five cycles of isolations and infusions of increasing numbers of CD8+ T cells were achieved in five of seven subjects. Five cycles could not be completed in two subjects with AIDS whose CD4+ cell counts were < or = 48/microliters. Infusions of CD8+ cells alone were well tolerated. Four patients received rIL-2 by continuous infusion for 5 days with their final cycle of CD8+ cells. All developed reversible adverse effects attributable to rIL-2. After infusion, 111In-labeled CD8+ cells quickly accumulated in the lungs, with less than 10% of the labeled cells remaining in the circulation. After 24 hours, labeled CD8+ cells were reduced in the lungs, but increased and persisted in liver, spleen, and bone marrow. Four of five patients who were treated with multiple infusions of CD8+ cells have improved or remained clinically stable, and the fifth developed Pneumocystis carinii pneumonia but recovered. This study demonstrated that infusion of autologous, in vitro expanded and activated CD8+ cells was feasible and clinically well tolerated in five of seven subjects with advanced HIV infections.
Ho
M
M
Department of Infectious Diseases and Microbiology, Graduate School of Public Health, PA 15261.
Armstrong
J
J
McMahon
D
D
Pazin
G
G
Huang
X L
XL
Rinaldo
C
C
Whiteside
T
T
Tripoli
C
C
Levine
G
G
Moody
D
D
D000386:AIDS-Related Complex / Q000628:therapy*; D000163:Acquired Immunodeficiency Syndrome / Q000628:therapy*; D000328:Adult; D000911:Antibodies, Monoclonal; D016827:CD8 Antigens / Q000276:immunology; D002469:Cell Separation; D002478:Cells, Cultured; D006678:HIV / Q000302:isolation & purification; D006801:Humans; D016219:Immunotherapy, Adoptive; D007376:Interleukin-2 / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D007937:Leukapheresis; D007958:Leukocyte Count; D008168:Lung / Q000166:cytology; D008213:Lymphocyte Activation; D010835:Phytohemagglutinins / Q000494:pharmacology; D011994:Recombinant Proteins / Q000494:pharmacology / Q000627:therapeutic use; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000637:transplantation*
D000911:Antibodies, Monoclonal; D016827:CD8 Antigens; D007376:Interleukin-2; D010835:Phytohemagglutinins; D011994:Recombinant Proteins