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Induction of CD8 T-cell-Ifn-γ response and positive clinical outcome after immunization with gene-modified allogeneic tumor cells in advanced non-small-cell lung carcinoma

Cancer Gene Therapy volume 10, pages 850–858 (2003)Cite this article

Abstract

Large tumor burdens in advanced non-small-cell lung carcinoma (NSCLC) are thought to be immunosuppressive. To determine whether CD8-mediated immune responses could be elicited in stage IIIB/IV NSCLC patients, 14 subjects were immunized several times with allogeneic NSCLC cells transfected with CD80 (B7.1) and HLA-A1 or A2. Patients enrolled were matched or unmatched at the HLA A1 or A2 locus and their immune response compared. Immunization significantly increased the frequencies of interferon-γ secreting CD8 T cells in all but one patient in response to ex vivo challenge with NSCLC cells. The CD8 response of matched and unmatched patients was not statistically different. NSCLC reactive CD8 cells did not react to K562. Clinically, five of 14 patients responded to immunization with stable disease or partial tumor regression. The study demonstrates that CD8 Ifn-γ responses against nonimmunogenic or immunosuppressive tumors can be evoked by cellular vaccines even at advanced stages of disease. The positive clinical outcome suggests that nonimmunogenic tumors may be highly susceptible to immune effector cells generated by immunization.

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Acknowledgements

We gratefully acknowledge support for this work from the family and friends of Iris Zeitler and the University of Miami Sylvester Comprehensive Cancer Center. LR is supported by a Clinical Career Development Award and SP by a Young Investigator Award from ASCO. Further support came from NIH Grant RO1-CA39201-14.

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Authors and Affiliations

  1. Department of Medicine, University of Miami School of Medicine, Miami, 33136, Florida, USA

    Luis E Raez, Peter A Cassileth, Swaminathan Padmanabhan, Paulette A Baldie & Kasi Sridhar

  2. Department of Epidemiology and Public Health, University of Miami School of Medicine, Miami, 33136, Florida, USA

    James J Schlesselman

  3. Department of Microbiology and Immunology, University of Miami School of Medicine, Miami, 33136, Florida, USA

    Eva Z Fisher & Eckhard R Podack

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  1. Luis E Raez
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Correspondence to Eckhard R Podack.

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Raez, L., Cassileth, P., Schlesselman, J. et al. Induction of CD8 T-cell-Ifn-γ response and positive clinical outcome after immunization with gene-modified allogeneic tumor cells in advanced non-small-cell lung carcinoma. Cancer Gene Ther 10, 850–858 (2003). https://doi.org/10.1038/sj.cgt.7700641

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