| Budget Amount *help |
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2001: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2000: ¥2,000,000 (Direct Cost: ¥2,000,000)
|
|---|
| Research Abstract |
A lck gene was identified by the gene-expression cloning method, in which a KE4-cytotoxic T cell (CTL) line was used. The KE4-CTL line was previously established from tumor-infiltrating lymphocytes (TILs) of squamous cell carcinoma. The Lck protein (p56k/c), a src family tyrosine kinase which is essential for T cell development and function, is aberrantly expressed in metastatic colon cancers. The type I transcript was used in the cancer cell lines, in agreement with the results reported previously, whereas the type II transcript was used in normal cells and tissues.Further, all p56^<lck> esophageal cancer cell lines were established from the primary esophageal tumors patients who had distinct metastases, including the KE4 tumor cells from which the lck gene was cloned as a gene encoding tumor-rejection antigen. p56^<lck> seems to facilitate the malignant transformation of epithelial cells through initiation of anchorage-independent proliferation. We identified three peptides (Lck208-216, Lck486-494, and Lck488-497), which were recognized by KE4-CTL. These Lck peptides augmented CTh activity in peripheral blood mononuclear cells of colon and other epithelial cancer patients with metastasis, but not those without metastasis. CTL precursors recognizing the Lck peptide were identified in freshly prepared PBMCs of metastatic cancer patients, and their frequency was significantly augmented by the stimulation with the peptide. Thus, Lck peptides could be useful for specific immunotherapy toward metastatic cancer patients.
|
