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 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 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.

• Authors: Paul Sabbatini, Takemasa Tsuji, Luis Ferran, Erika Ritter, Christine Sedrak, Kevin Tuballes, Achim A Jungbluth, Gerd Ritter, Carol Aghajanian, Katherine Bell-McGuinn, Martee L Hensley, Jason Konner, William Tew, David R Spriggs, Eric W Hoffman, Ralph Venhaus, Linda Pan, Andres M Salazar, Catherine Magid Diefenbach, Lloyd J Old, Sacha Gnjatic
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 18 Issue 23 Pg. 6497-508 (Dec 01 2012) ISSN: 1557-3265 [Electronic] United States
• PMID: 23032745 (Publication Type: Clinical Trial, Phase II, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: ©2012 AACR.

Chemical References

• Antibodies
• Antigens, Neoplasm
• Autoantigens
• Cancer Vaccines
• Peptides
• Vaccines, Subunit
• Polylysine
• poly ICLC
• Carboxymethylcellulose Sodium
• Poly I-C

Topics

• Adult
• Aged
• Antibodies (immunology)
• Antigens, Neoplasm (chemistry, immunology)
• Autoantigens (chemistry, immunology)
• CD4-Positive T-Lymphocytes (immunology)
• CD8-Positive T-Lymphocytes (immunology)
• Cancer Vaccines (administration & dosage, adverse effects, immunology)
• Carboxymethylcellulose Sodium (analogs & derivatives)
• Female
• Follow-Up Studies
• Humans
• Immunity, Humoral
• Middle Aged
• Neoplasm Staging
• Ovarian Neoplasms (immunology, pathology, therapy)
• Peptides (immunology)
• Poly I-C (immunology)
• Polylysine (analogs & derivatives, immunology)
• T-Lymphocytes, Regulatory (immunology)
• Treatment Outcome
• Vaccines, Subunit (administration & dosage, adverse effects, immunology)