Immunization of malignant melanoma patients with full-length NY-ESO-1 protein using TLR7 agonist imiquimod as vaccine adjuvant

Sylvia Adams, David W. O'Neill, Daisuke Nonaka, Elizabeth Hardin, Luis Chiriboga, Kimberly Siu, Crystal M. Cruz, Angelica Angiulli, Francesca Angiulli, Erika Ritter, Rose Marie Holman, Richard L. Shapiro, Russell S. Berman, Natalie Berner, Yongzhao Shao, Olivier Manches, Linda Pan, Ralph R. Venhaus, Eric W. Hoffman, Achim JungbluthSacha Gnjatic, Lloyd Old, Anna C. Pavlick, Nina Bhardwaj

Research output: Contribution to journalArticle

192 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)776-784
Number of pages9
JournalJournal of Immunology
Volume181
Issue number1
DOIs
StatePublished - Jan 1 2008
Externally publishedYes

    Fingerprint

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Adams, S., O'Neill, D. W., Nonaka, D., Hardin, E., Chiriboga, L., Siu, K., Cruz, C. M., Angiulli, A., Angiulli, F., Ritter, E., Holman, R. M., Shapiro, R. L., Berman, R. S., Berner, N., Shao, Y., Manches, O., Pan, L., Venhaus, R. R., Hoffman, E. W., ... Bhardwaj, N. (2008). Immunization of malignant melanoma patients with full-length NY-ESO-1 protein using TLR7 agonist imiquimod as vaccine adjuvant. Journal of Immunology, 181(1), 776-784. https://doi.org/10.4049/jimmunol.181.1.776