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. Ā©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"
Altmetric Score
MSK Authors
  1. Larry M Pan
    6 Pan
  2. Jason Konner
    84 Konner
  3. Paul J Sabbatini
    199 Sabbatini
  4. Martee L Hensley
    220 Hensley
  5. William P Tew
    122 Tew
  6. David R Spriggs
    308 Spriggs
  7. Sacha Gnjatic
    111 Gnjatic
  8. Achim Jungbluth
    337 Jungbluth
  9. Gerd Ritter
    156 Ritter
  10. Erika Ritter
    34 Ritter
  11. Takemasa Tsuji
    14 Tsuji
  12. Lloyd J Old
    381 Old
  13. Christine Sedrak
    4 Sedrak
  14. Luis Ferran
    1 Ferran