Journal
JOURNAL OF IMMUNOTHERAPY
Volume 31, Issue 4, Pages 420-430Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/CJI.0b013e31816dad10
Keywords
peptide; ovarian cancer; tumor immunity; vaccine; phase 1 clinical trial
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Funding
- NCI NIH HHS [P30 CA44579] Funding Source: Medline
- NCRR NIH HHS [5 M01 RR00847] Funding Source: Medline
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Nine participants with epithelial ovarian, fallopian tube, or primary peritoneal carcinoma, who were human leukocyte antigen (HLA)-A1(+), HLA-A2(+), or HLA-A3(+), were eligible to enroll in a phase I study designed to assess the safety and immunogenicity of a peptide-based vaccine. Participants received 5 class I major histocompatibility complex-restricted synthetic peptides derived from multiple ovarian cancer-associated proteins plus a class 11 major histocompatibility complex-restricted synthetic helper peptide derived from tetanus toxoid protein. The vaccines were administered with granulocyte macrophage-colony stimulating factor in Montanide ISA-51 adjuvant over a 7-week period. All vaccine-related toxicities were grade I to 2, the most common being injection site reaction (grade 2, 100%), fatigue (grade 1, 78%), and headache (grade 1, 67%). Lymphocytes from the peripheral blood and a node draining a secondary vaccine site (sentinel immunized node) were harvested during the course of vaccination and T-cell responses to the peptides were evaluated using an enzyme-linked immunosorbent spot assay. CD8(+) T-cell responses were detected in I participant ex vivo and in 8 of 9 participants (89%) after in vitro stimulation. All 4 HLA-A2 and HLA-A3-restricted peptides were immunogenic. This includes 2 peptides, folate binding protein (FBP191-199) and Her-2/ neU(754-762), which had not previously been evaluated in vaccines in humans. Responding T cells required over 200 nM for halfmaximal reactivity. These data support continued investigation of these peptides as immunogens for patients with ovarian cancer but, owing to low potency, also suggest a need for additional immunomodulation in combination with vaccines to increase the magnitude and to improve the quality of the T-cell responses.
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