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Induction of human cytotoxic T lymphocytes by artificial antigen-presenting cells

Abstract

The adoptive transfer of antigen-specific cytotoxic T lymphocytes (CTLs) is a promising therapeutic approach for a number of diseases. To overcome the difficulty in generating specific CTLs, we established stable artificial antigen-presenting cells (AAPCs) that can be used to stimulate T cells of any patient of a given human leukocyte antigen (HLA) type. Mouse fibroblasts were retrovirally transduced with a single HLA–peptide complex along with the human accessory molecules B7.1, ICAM-1, and LFA-3. These AAPCs consistently elicit strong stimulation and expansion of HLA-restricted CTLs. Owing to the high efficiency of retrovirus-mediated gene transfer, stable AAPCs can be readily engineered for any HLA molecule and any specific peptide.

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Figure 1: Generation of AAPCs from mouse fibroblasts.
Figure 2: Stimulation of peripheral blood cytotoxic T cells against the flu peptide.
Figure 3: Expansion of primary CD8+ T cells stimulated with AAPCA2F or flu peptide-pulsed autologous dendritic cells.
Figure 4: Artificial APCs induce cytotoxic T-cell responses against tumor antigens.
Figure 5: Cytotoxic T-lymphocyte induction against tumor antigens in different HLA A2.1+ donors.
Figure 6: HLA-restricted cytolysis of melanoma cells by CTLs induced by AAPCA2G and AAPCA2M.

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Acknowledgements

We thank C. Tan (Gene Transfer and Somatic Cell Engineering Facility, MSKCC) for excellent technical assistance, T. Delohery (Flow Cytometry Core Facility, MSKCC) for excellent assistance with cell sorting, and Dr. I. Rivière for reviewing the manuscript. This work was supported by grant CA-59350, the Dewitt Wallace Fund, and the McDonnell Scholars Award for Molecular Medicine (M.S.).

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Correspondence to Michel Sadelain.

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Latouche, JB., Sadelain, M. Induction of human cytotoxic T lymphocytes by artificial antigen-presenting cells. Nat Biotechnol 18, 405–409 (2000). https://doi.org/10.1038/74455

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