Effect of granulocyte/macrophage colony-stimulating factor on vaccination with an allogeneic whole-cell melanoma vaccine.
Effect of granulocyte/macrophage colony-stimulating factor on vaccination with an allogeneic whole-cell melanoma vaccine.
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DOI：
10.1158/1078-0432.ccr-09-1540
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发表时间：
2009-11-15
期刊：
影响因子：
--
通讯作者：
Morton DL
中科院分区：
文献类型：
--
作者：
Faries MB;Hsueh EC;Ye X;Hoban M;Morton DL
The availability of a variety of immune response modifiers creates an opportunity for improved efficacy of immunotherapy, but it also leads to uncertainty in how to combine agents and how to assess those combinations. We sought to assess the impact of the addition of GM-CSF to vaccination with a melanoma vaccine. Ninety-seven patients with resected melanoma (Stage II-IV) were enrolled, stratified by stage and randomized to receive a cellular melanoma vaccine with or without GM-CSF. The primary endpoint was delayed-type hypersensitivity (DTH) response to melanoma cells. Antibody responses, peripheral leukocyte counts and survival were also examined. The GM-CSF arm demonstrated enhanced antibody responses with an increase in IgM titer against the TA90 antigen and increased TA90 immune complexes. This arm also had diminished anti-melanoma cell DTH response. Peripheral blood leukocyte profiles showed increases in eosinophils and basophils with decreased monocytes in the GM-CSF arm. These immune changes were accompanied by an increase in early melanoma deaths and a trend toward worse survival with GM-CSF. These data suggest that GM-CSF is not helpful as an immune adjuvant in this dose and schedule, and raise concern that it may be harmful. Based upon the discordant findings of an immune endpoint and clinical outcome, use of such surrogate endopoints in selecting treatments for further evaluation must be done with a great deal of caution.
