TY - JOUR
T1 - Immunization of malignant melanoma patients with full-length NY-ESO-1 protein using TLR7 agonist imiquimod as vaccine adjuvant
AU - Adams, Sylvia
AU - O'Neill, David W.
AU - Nonaka, Daisuke
AU - Hardin, Elizabeth
AU - Chiriboga, Luis
AU - Siu, Kimberly
AU - Cruz, Crystal M.
AU - Angiulli, Angelica
AU - Angiulli, Francesca
AU - Ritter, Erika
AU - Holman, Rose Marie
AU - Shapiro, Richard L.
AU - Berman, Russell S.
AU - Berner, Natalie
AU - Shao, Yongzhao
AU - Manches, Olivier
AU - Pan, Linda
AU - Venhaus, Ralph R.
AU - Hoffman, Eric W.
AU - Jungbluth, Achim
AU - Gnjatic, Sacha
AU - Old, Lloyd
AU - Pavlick, Anna C.
AU - Bhardwaj, Nina
PY - 2008
Y1 - 2008
N2 - T cell-mediated immunity to microbes and to cancer can be enhanced by the activation of dendritic cells (DCs) via TLRs. In this study, we evaluated the safety and feasibility of topical imiquimod, a TLR7 agonist, in a series of vaccinations against the cancer/testis Ag NY-ESO-1 in patients with malignant melanoma. Recombinant, full-length NY-ESO-1 protein was administered intradermally into imiquimod preconditioned sites followed by additional topical applications of imiquimod. The regimen was very well tolerated with only mild and transient local reactions and constitutional symptoms. Secondarily, we examined the systemic immune response induced by the imiquimod/NY-ESO-1 combination, and show that it elicited both humoral and cellular responses in a significant fraction of patients. Skin biopsies were assessed for imiquimod's in situ immunomodulatory effects. Compared with untreated skin, topical imiquimod induced dermal mononuclear cell infiltrates in all patients composed primarily of T cells, monocytes, macrophages, myeloid DCs, NK cells, and, to a lesser extent, plasmacytoid DCs. DC activation was evident. This study demonstrates the feasibility and excellent safety profile of a topically applied TLR7 agonist used as a vaccine adjuvant in cancer patients. Imiquimod's adjuvant effects require further evaluation and likely need optimization of parameters such as formulation, dose, and timing relative to Ag exposure for maximal immunogenicity.
AB - T cell-mediated immunity to microbes and to cancer can be enhanced by the activation of dendritic cells (DCs) via TLRs. In this study, we evaluated the safety and feasibility of topical imiquimod, a TLR7 agonist, in a series of vaccinations against the cancer/testis Ag NY-ESO-1 in patients with malignant melanoma. Recombinant, full-length NY-ESO-1 protein was administered intradermally into imiquimod preconditioned sites followed by additional topical applications of imiquimod. The regimen was very well tolerated with only mild and transient local reactions and constitutional symptoms. Secondarily, we examined the systemic immune response induced by the imiquimod/NY-ESO-1 combination, and show that it elicited both humoral and cellular responses in a significant fraction of patients. Skin biopsies were assessed for imiquimod's in situ immunomodulatory effects. Compared with untreated skin, topical imiquimod induced dermal mononuclear cell infiltrates in all patients composed primarily of T cells, monocytes, macrophages, myeloid DCs, NK cells, and, to a lesser extent, plasmacytoid DCs. DC activation was evident. This study demonstrates the feasibility and excellent safety profile of a topically applied TLR7 agonist used as a vaccine adjuvant in cancer patients. Imiquimod's adjuvant effects require further evaluation and likely need optimization of parameters such as formulation, dose, and timing relative to Ag exposure for maximal immunogenicity.
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U2 - 10.4049/jimmunol.181.1.776
DO - 10.4049/jimmunol.181.1.776
M3 - Article
C2 - 18566444
AN - SCOPUS:47949129948
SN - 0022-1767
VL - 181
SP - 776
EP - 784
JO - Journal of Immunology
JF - Journal of Immunology
IS - 1
ER -