We previously identified three novel HLA-A24-restricted
epitope peptides, which were
derived from three cancer-testis
antigens, TTK
protein kinase (TTK),
lymphocyte antigen 6 complex locus K (LY6K), and
insulin-like growth factor (IGF)-II
mRNA binding protein 3 (IMP-3), as targets for cancer
vaccination against esophageal
squamous cell carcinoma (
ESCC). To examine the safety,
immunogenicity, and
antitumor effect of
vaccine treatment using a combination of these three
peptides, 10 HLA-A2402-positive advanced
ESCC patients who failed to standard therapy were enrolled in a
phase I clinical trial. Each of the three
peptides (1 mg each) was intradermally administered with 1 mL of incomplete
Freund's adjuvant to the
neck in three separate regions weekly for 5 weeks. The cancer
vaccination therapy was well tolerated without any treatment-associated
adverse events of grade 3 or 4. The TTK-, LY6K-, and/or IMP-3-specific
T-cell immune responses were observed by enzyme-linked immunospot
assay in
peripheral blood lymphocytes obtained from nine of the 10
ESCC patients after their
vaccination. The
median survival time after the
vaccination was 6.6 months. The
vaccination could induce good clinical responses in 50% of the 10 patients. One patient experienced a complete response in
hepatic metastasis lasting 7 months, one showed objective responses in all
lung metastasis lesions, and three patients revealed a stable disease condition for at least 2.5 months. The
cancer vaccine therapy using these three
peptides demonstrated satisfactory safety and good
immunogenicity as well as promising disease control rate, and therefore warrants further
clinical studies.
