Immunization of HLA-A2+ Melanoma Patients with MAGE-3 or MelanA Peptide-pulsed Autologous Peripheral Blood Mononuclear Cells Plus Recombinant Human Interleukin 12

作者: Francesca Fallarino , Thomas F. Gajewski , Andrew Ashikari , Matthew Sherman

DOI:

关键词: Antigen presentationInterleukin 12Tumor antigenMART-1 AntigenAntigenDendritic cellImmunologyCellular immunityPeripheral blood mononuclear cellMedicine

摘要: Vaccination with dendritic cells (DCs) pulsed tumor antigen peptides has shown promise in the treatment of melanoma. Interleukin (IL)-12 production by DCs is a key component for their efficacy. Murine studies have that IL-12 promotes potent antitumor immunization when coadministered loaded onto other class I MHC+ cells, thus bypassing need to use DCs. The easiest cell source obtain large quantity from human patients peripheral blood mononuclear (PBMCs). A Phase clinical trial was performed metastatic melanoma using autologous PBMCs MAGE-3 or MelanA peptide, various doses recombinant (rh)IL-12. Patients receiving low-to-moderate rhIL-12 developed increased specific CD8+ T-cell responses. Of eight showing immunity, six had evidence activity, one complete, partial, minor, and three mixed responses observed. In two responses, growing tumors were found lack expression used immunize. Thus, vaccination peptide-pulsed plus induces immunity without generate Outgrowth antigen-negative argues future development polyepitope vaccines.

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