DEVELOPMENT OF NEW CANCER VACCINE THERAPY AGAINST LUNG CANCER

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Abstract

We have established a strategy as follows to identify oncoantigens and HLA-restricted epitope peptides, which can be applied as cancer vaccine therapy; (i) to identify genes overexpressed in 120 clinical lung cancers using the cDNA microarray representing 27 648 genes, (ii) to validate the clinicopathological significance of their protein expression by tissue microarray covering 1300 cases of lung cancers, (iii) to verify whether they are essential for the growth of cancer cells by siRNAs, (iv) to screen for the epitope peptides recognized by human HLA-A*0201/A*2402-restricted cytotoxic T lymphocyte (CTL) by ELISPOT assay in the list of these oncoantigens. We identified dozens of HLA-A*2402- or -A*0201-restricted epitope peptides, which were derived from cancer-testis antigens essential for the growth and/or survival of cancer cells, as targets for cancer vaccination against lung cancer. In a phase I trial, we examined using a combination of three peptides the safety, immunogenicity, and antitumor effect of vaccine treatment of HLA-A*2402- or -A*0201-positive advanced lung cancer patients who failed to standard therapy. The cancer vaccine therapy using these three peptides demonstrated safety and good immunogenicity as well as promising disease control rate, and therefore warrants further clinical studies. In this session, we also introduce and discuss on-going International Conference on Harmonization (ICH)-Good Clinical Practice (GCP)-based clinical study in patients with lung cancer refractory to standard therapy.

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