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Prepublished online as a Blood First Edition Paper on June 12, 2003; DOI 10.1182/blood-2003-02-0345.
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Blood, 1 October 2003, Vol. 102, No. 7, pp. 2498-2505
IMMUNOBIOLOGY
Rapid expansion of cytomegalovirus–specific cytotoxic T lymphocytes by artificial antigen-presenting cells expressing a single HLA allele
Genovefa A. Papanicolaou,
Jean-Baptiste Latouche,
Cuiwen Tan,
Jakob Dupont,
Jeffrey Stiles,
Eric G. Pamer, and
Michel Sadelain
From the Department of Medicine, the Immunology Program, and the Gene Transfer and Somatic Cell Engineering Laboratory, Memorial Sloan-Kettering Cancer Center, New York, NY.
Cytomegalovirus (CMV) is a major threat in patients undergoing allogeneic bone marrow transplantation. The adoptive transfer of CMV-specific cytotoxic T lymphocytes (CTLs) expanded from the blood of CMV-seropositive donors has been shown to effectively control CMV infection. However, the requirement for safe and effective antigen-presenting cells (APCs) for each patient precludes broad applicability of this successful form of therapy. Here we analyze the ability of artificial APCs (AAPCs) to activate and expand CMV-specific CTLs from peripheral blood of seropositive HLA A2.1+ donors. We demonstrate that AAPCs expressing the CMV P495 peptide or the full-length pp65 protein stimulate P495-specific CTLs at least as effectively as autologous, peptide-pulsed, peripheral blood mononuclear cells or EBV-transformed B cells. Starting from 100 mL of blood, the AAPCs reliably yield clinically relevant CTL numbers after a single stimulation. CTLs activated on AAPCs effectively kill CMV-infected fibroblasts and have a Tc1 memory effector phenotype identical to that of CTLs generated with autologous APCs. AAPCs thus offer a rapid, controlled, convenient, and highly reproducible system for expanding CMV-specific CTLs. Furthermore, the CTL expansion obtained with AAPCs encoding full-length pp65 indicates that AAPCs may be used to present known as well as unknown CTL epitopes in the context of the AAPC's HLA. (Blood. 2003;102:2498-2505)
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