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Enhancement of Cytolytic T Lymphocyte Precursor Frequency in Melanoma Patients following Immunization with the MAGE-1 Peptide Loaded Antigen Presenting Cell-based Vaccine¹

Departments of Medicine [X. H., N. G. C., J. R. S., B. M.] and Surgery [S. H. K., M. T. E.], University of Connecticut School of Medicine, Farmington, Connecticut 06030

Identification of human melanoma-associated peptide antigens for CTLs has opened unprecedented opportunities for active specific immunotherapy for melanoma with synthetic peptide. We have shown that immunization with a MAGE-1 gene encoded nonapeptide (EADPT-GHSY)-pulsed autologous antigen presenting cell-based vaccine induces autologous melanoma-reactive and peptide-specific CTL response, in situ, at the vaccination site and at distant tumor deposits in patients who are HLA-A1+ and whose melanoma cells express the MAGE-1 mRNA. Here, we show that such immunization is also capable of increasing the frequency of autologous melanoma-reactive CTL precursors in the circulation. We further show that in vitro stimulation of the postimmunization peripheral blood lymphocytes with the MAGE-1 nonapeptide-loaded antigen presenting cell and interleukin-2 leads to significant expansion of peptide-specific and autologous melanoma-reactive CTL response.

¹ The work was supported by United States Public Health Service Grant CA 61398 from the National Cancer Institute, in part by United States Public Health Service Grant MO1-RR 06192 from the NIH, and in part by the Lavery Memorial Research Fund.

² To whom requests for reprints should be addressed, at University of Connecticut School of Medicine, 263 Farmington Avenue, Farmington, CT 06030-3210.

Received 3/27/96. Accepted 4/25/96.

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