Hasan, AN, Kollen, WJ, Trivedi, D, Selvakumar, A, Dupont, B, Sadelain, M et al.. A panel of artificial APCs expressing prevalent HLA alleles permits generation of cytotoxic T cells specific for both dominant and subdominant viral epitopes for adoptive therapy. J Immunol 183: 2837-2850

Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
The Journal of Immunology (Impact Factor: 4.92). 09/2009; 183(4):2837-50. DOI: 10.4049/jimmunol.0804178
Source: PubMed


Adoptive transfer of virus-specific T cells can treat infections complicating allogeneic hematopoietic cell transplants. However, autologous APCs are often limited in supply. In this study, we describe a panel of artificial APCs (AAPCs) consisting of murine 3T3 cells transduced to express human B7.1, ICAM-1, and LFA-3 that each stably express one of a series of six common HLA class I alleles. In comparative analyses, T cells sensitized with AAPCs expressing a shared HLA allele or autologous APCs loaded with a pool of 15-mer spanning the sequence of CMVpp65 produced similar yields of HLA-restricted CMVpp65-specific T cells; significantly higher yields could be achieved by sensitization with AAPCs transduced to express the CMVpp65 protein. T cells generated were CD8(+), IFN-gamma(+), and exhibited HLA-restricted CMVpp65-specific cytotoxicity. T cells sensitized with either peptide-loaded or transduced AAPCs recognized epitopes presented by each HLA allele known to be immunogenic in humans. Sensitization with AAPCs also permitted expansion of IFN-gamma(+) cytotoxic effector cells against subdominant epitopes that were either absent or in low frequencies in T cells sensitized with autologous APCs. This replenishable panel of AAPCs can be used for immediate sensitization and expansion of virus-specific T cells of desired HLA restriction for adoptive immunotherapy. It may be of particular value for recipients of transplants from HLA-disparate donors.

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    • "Using overlapping pentadecapeptides expressing components of the CMVpp65 epitope, Dr. O'Reilly's group loaded autologous dendritic cells (DCs) with 15-mers and sensitized T cells prior to adoptive therapy for drug resistant CMV. Peptides that cause increased gamma interferon (IFNγ ) release by T cells were considered immunodominant [2]. In a phase I trial, they observed that 70% of patients cleared their infection, and it took about 18 to 20 days to observe a response. "
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