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

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

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  • Media type: E-Article
  • Title: 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
  • Contributor: Sabbatini, Paul; Tsuji, Takemasa; Ferran, Luis; Ritter, Erika; Sedrak, Christine; Tuballes, Kevin; Jungbluth, Achim A.; Ritter, Gerd; Aghajanian, Carol; Bell-McGuinn, Katherine; Hensley, Martee L.; Konner, Jason; Tew, William; Spriggs, David R.; Hoffman, Eric W.; Venhaus, Ralph; Pan, Linda; Salazar, Andres M.; Diefenbach, Catherine Magid; Old, Lloyd J.; Gnjatic, Sacha
  • imprint: American Association for Cancer Research (AACR), 2012
  • Published in: Clinical Cancer Research
  • Language: English
  • DOI: 10.1158/1078-0432.ccr-12-2189
  • ISSN: 1078-0432; 1557-3265
  • Origination:
  • Footnote:
  • Description: <jats:title>Abstract</jats:title> <jats:p>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.</jats:p> <jats:p>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).</jats:p> <jats:p>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.</jats:p> <jats:p>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.</jats:p>
  • Access State: Open Access