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Thursday, October 04, 2012

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



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

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 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 advanced ovarian cancer patients in second or third remission were enrolled sequentially in 3 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, 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 found in 6/13 (46%) and 8/13 (62%) patients respectively after vaccination with OLP+Montanide, and in 10/11 (91%) and 10/11 (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 adjuvant further accelerated induction of NY-ESO-1-specific immune responses.

CONCLUSIONS: The current study demonstrates 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.



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