Phase I trial of overlapping long peptides from a tumor self-antigen and poly-ICLC shows rapid induction of integrated immune response in ovarian cancer patients

Paul Sabbatini, Takemasa Tsuji, Luis Ferran, Erika Ritter, Christine Sedrak, Kevin Tuballes, Achim A. Jungbluth, Gerd Ritter, Carol Aghajanian, Katherine Bell-McGuinn, Martee L. Hensley, Jason Konner, William Tew, David R. Spriggs, Eric W. Hoffman, Ralph Venhaus, Linda Pan, Andres M. Salazar, Catherine Magid Diefenbach, Lloyd J. OldSacha Gnjatic

Research output: Contribution to journalArticlepeer-review

201 Scopus citations

Abstract

Purpose: Long peptides are efficiently presented to both CD4+ and CD8+T cells after intracellular processing by antigen-presenting cells. To investigate the safety and in vivo immunogenicity of synthetic overlapping long peptides (OLP) from ahumantumor self-antigen, we conducted a phase I clinical trial with OLP from cancer-testis antigen NY-ESO-1 in various adjuvant combinations. Experimental Design: Twenty-eight patients with advanced ovarian cancer in second or third remission were enrolled sequentially in three cohorts and received at least one vaccination. Patients in Cohort 1 (n = 4) received 1.0 mg OLP, Cohort 2 (n = 13) received OLP in Montanide-ISA-51, and Cohort 3 (n = 11) received OLP+ 1.4 mg Poly-ICLC in Montanide-ISA-51 on weeks 1, 4, 7, 10, and 13. Humoral and cellular responses were evaluated by standardized immunomonitoring techniques (ELISA, ELISPOT assay, intracellular cytokine staining, and tetramer staining). Results: The vaccine was generally well tolerated with injection site reactions and fatigue that resolved. NY-ESO-1-specific antibody and CD8+ T cells were undetectable after vaccination with OLP alone, but were found in 6 of 13 (46%) and 8 of 13 (62%) patients, respectively, after vaccination with OLP+Montanide, and in 10 of 11 (91%) and 10 of 11 (91%) patients, respectively, after vaccination with OLP+Montanide+Poly-ICLC. NY-ESO-1-specific CD4+ T cells were detected in all patients with greater frequency and polyclonality when Montanide-ISA-51 was used for vaccination. Inclusion of Poly-ICLC as an adjuvant further accelerated the induction of NY-ESO-1-specific immune responses. Conclusions: The current study shows that NY-ESO-1 OLP vaccine is safe and rapidly induces consistent integrated immune responses (antibody, CD8+ and CD4 +) in nearly all vaccinated patients when given with appropriate adjuvants.

Original languageEnglish
Pages (from-to)6497-6508
Number of pages12
JournalClinical Cancer Research
Volume18
Issue number23
DOIs
StatePublished - 1 Dec 2012
Externally publishedYes

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