PT  - JOURNAL ARTICLE
AU  - Sabbatini, Paul
AU  - Tsuji, Takemasa
AU  - Ferran, Luis
AU  - Ritter, Erika
AU  - Sedrak, Christine
AU  - Tuballes, Kevin
AU  - Jungbluth, Achim A.
AU  - Ritter, Gerd
AU  - Aghajanian, Carol
AU  - Bell-McGuinn, Katherine
AU  - Hensley, Martee L.
AU  - Konner, Jason
AU  - Tew, William
AU  - Spriggs, David R.
AU  - Hoffman, Eric W.
AU  - Venhaus, Ralph
AU  - Pan, Linda
AU  - Salazar, Andres M.
AU  - Diefenbach, Catherine Magid
AU  - Old, Lloyd J.
AU  - Gnjatic, Sacha
TI  - 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
AID  - 10.1158/1078-0432.CCR-12-2189
DP  - 2012 Dec 01
TA  - Clinical Cancer Research
PG  - 6497--6508
VI  - 18
IP  - 23
4099  - http://clincancerres.aacrjournals.org/content/18/23/6497.short
4100  - http://clincancerres.aacrjournals.org/content/18/23/6497.full
SO  - Clin Cancer Res2012 Dec 01; 18
AB  - 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 a human tumor 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. Clin Cancer Res; 18(23); 6497–508. ©2012 AACR.