Cancer Therapy: Clinical Phase I Trial ofOverlappingLongPeptides fromaTumorSelf- Antigen and Poly-ICLC Shows Rapid Induction of Integrated Immune Response in Ovarian Cancer Patients
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چکیده
Purpose: Long peptides are efficiently presented to both CD4þ and CD8þ T cells after intracellular processing by antigen-presenting cells. To investigate the safety and in vivo immunogenicity of synthetic overlapping longpeptides (OLP) fromahuman tumor self-antigen,we conducted aphase I clinical trialwith 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 inCohort 1 (n1⁄44) received 1.0mgOLP, Cohort 2 (n1⁄4 13) receivedOLP inMontanide-ISA-51, andCohort 3 (n1⁄4 11) received OLPþ 1.4mgPoly-ICLC inMontanide-ISA-51 onweeks 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 andCD8þ T cellswere undetectable after vaccinationwithOLP alone, butwere found in 6 of 13 (46%) and 8 of 13 (62%) patients, respectively, after vaccination with OLPþMontanide, and in 10 of 11 (91%) and 10 of 11 (91%) patients, respectively, after vaccination with OLPþMontanideþPoly-ICLC. NY-ESO-1–specific CD4þ T cells were detected in all patients with greater frequency andpolyclonalitywhenMontanide-ISA-51was used for vaccination. Inclusionof Poly-ICLCas an adjuvant further accelerated the induction of NY-ESO-1–specific immune responses. Conclusions: The current study shows that NY-ESO-1OLP vaccine is safe and rapidly induces consistent integrated immune responses (antibody,CD8þ andCD4þ) innearly all vaccinatedpatientswhen givenwith appropriate adjuvants. Clin Cancer Res; 18(23); 6497–508. 2012 AACR.
منابع مشابه
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.
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. EXPER...
متن کاملEffect of Montanide and poly-ICLC adjuvant on human self/tumor antigen-specific CD4+ T cells in phase I overlapping long peptide vaccine trial.
Vaccination of patients with ovarian cancer with overlapping long peptides (OLP) from cancer-testis antigen NY-ESO-1 and poly-ICLC in Montanide-ISA-51 (Montanide) was found to consistently induce integrated immune responses (antibody, CD4(+), and CD8(+) T cells). Using detailed methods, we investigated the respective effects of poly-ICLC and Montanide adjuvant on pre- and postvaccine NY-ESO-1-s...
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