Potential role of granulocyte-macrophage colony-stimulating factor as vaccine adjuvant

Abstract

The uses of GM-CSF as an immunomodulator and vaccine adjuvant are reviewed. GM-CSF has a variety of effects on immune responses: it induces class II major histocompatibility complex antigen expression on the surface of macrophages; it enhances dendritic cell maturation and migration; it results in a localized inflammation at the injection site; and it has marked effects on maturation of haematopoietic progenitor cells in the bone marrow. Animal and human studies suggest that administration of GM-CSF can increase antibody titres to foreign antigens. Monkeys injected with human interleukin (IL)-3 plus GM-CSF, at a different injection site, developed peak antibody titres which were 8- to 30-fold higher than those in monkeys injected with IL-3 alone. In a study of ovarian cancer patients receiving GM-CSF to prevent chemotherapy-induced neutropenia, two patients who had demonstrated a low titre of antithyroid antibodies prior to the study showed an increase in antibody titre and transient thyroiditis after administration of GM-CSF. Recently a GM-CSF/antigen fusion protein has been tested. An antibody corresponding to a specific idiotype expressed on B-cell lymphomas was fused to GM-CSF and injected into mice with B-cell lymphoma xenografts. The mice developed antibodies to the lymphoma and there was a protective effect against disease progression. Preliminary results of clinical trials using GM-CSF in humans suggest that it enhances antibody responses to hepatitis B vaccine. On the basis of these preliminary results, several clinical trials are being planned and it would appear that GM-CSF has potential as a vaccine adjuvant.