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 Journal Article
| Authors: | Sabbatini, P.; Tsuji, T.; Ferran, L.; Ritter, E.; Sedrak, C.; Tuballes, K.; Jungbluth, A. A.; Ritter, G.; Aghajanian, C.; Bell-Mcguinn, K.; Hensley, M. L.; Konner, J.; Tew, W.; Spriggs, D. R.; Hoffman, E. W.; Venhaus, R.; Pan, L.; Salazar, A. M.; Diefenbach, C. M.; Old, L. J.; Gnjatic, S. |
| 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 |
| 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. ©2012 AACR. |
| Journal Title: | Clinical Cancer Research |
| Volume: | 18 |
| Issue: | 23 |
| ISSN: | 1078-0432 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 2012-12-01 |
| Start Page: | 6497 |
| End Page: | 6508 |
| Language: | English |
| DOI: | 10.1158/1078-0432.ccr-12-2189 |
| PROVIDER: | scopus |
| PUBMED: | 23032745 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 2 January 2013" - "CODEN: CCREF" - "Source: Scopus" |
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