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Critical Reviews™ in Oncogenesis
SJR: 0.631 SNIP: 0.503 CiteScore™: 2

ISSN Imprimer: 0893-9675
ISSN En ligne: 2162-6448

Critical Reviews™ in Oncogenesis

DOI: 10.1615/CritRevOncog.v6.i3-6.10
pages 179-234

Adoptive CD8+ T-Cell Immunotherapy of AIDS Patients with Kaposi's Sarcoma

Roberto Patarca
Cordis Corporation, Miami Lakes, FL 33014
Nancy G. Klimas
E.M. Papper Laboratory of Clinical Immunology and Molecular Biology, University of Miami School of Medicine, Miami, Florida, USA
Jean Walling
Departments of Medicine and Microbiology & Immunology, E. M. Papper Laboratory of Clinical Immunology, University of Miami School of Medicine, P.O. Box 016960 (R-42), Miami, FL 33101
Dmitry Sandler
Departments of Medicine and Microbiology & Immunology, E. M. Papper Laboratory of Clinical Immunology, University of Miami School of Medicine, P.O. Box 016960 (R-42), Miami, FL 33101
Adam Friedlander
Departments of Medicine and Microbiology & Immunology, E. M. Papper Laboratory of Clinical Immunology, University of Miami School of Medicine, P.O. Box 016960 (R-42), Miami, FL 33101
Xue-Qin Jin
Departments of Medicine and Microbiology & Immunology, E. M. Papper Laboratory of Clinical Immunology, University of Miami School of Medicine, P.O. Box 016960 (R-42), Miami, FL 33101
Maria Nieves Garcia
Departments of Medicine and Microbiology & Immunology, E. M. Papper Laboratory of Clinical Immunology, University of Miami School of Medicine, P.O. Box 016960 (R-42), Miami, FL 33101
Mary Ann Fletcher
Departments of Medicine, and Microbiology and Immunology, University of Miami School of Medicine, E.M. Papper Laboratory of Clinical Immunology, P.O. Box 016960 (R-42), Miami, FL33101

RÉSUMÉ

This article reviews published and original findings from two clinical trials of adoptive CD8+ T-cell immunotherapy of patients with acquired immunodeficiency syndrome (AIDS) and Kaposi's sarcoma (KS). In the first trial, AIDS patients with either KS or oral hairy leukoplakia (OHL) received five rounds of reinfusions of 108 − 1010 ex vivo expanded and activated autologous CD8+ T cells. Recombinant interleukin-2 (rIL-2) was coadministered only with the fifth and final infusion. Improvement, and in some cases, resolution of OHL, KS, and candidiasis was observed with no side effects. The observation that clinical improvement of KS was more pronounced when reinfusion of CD8+ T cells was followed by rIL-2 infusion led to a second clinical trial designed to examine the effect of repeated infusions of autologous CD8+ T cells with concomitant rIL-2 administration in the treatment of AIDS-related KS. Improvement of KS status was observed in four out of the eight patients studied (three partial and one complete response). The CD8+ T-cell immunotherapy protocol also provided the opportunity to comparatively study CD8+ T-cell-associated genetic programs. Baseline expression patterns of soluble and surface immune markers by CD8+ T cells from AIDS patients and uninfected controls were predominantly of the type 1 type and differed mainly at a quantitative or kinetic level. Deficiencies in immune mediator expression by CD8+ T cells from AIDS patients tended to dissipate with progression through the protocol. Findings are discussed in the context of current knowledge and therapeutic implications of CD8+ T-cell function in AIDS and neoplasia.


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