1. Dendritic/pancreatic carcinoma fusions for clinical use: Comparative functional analysis of healthy- versus patient-derived fusions
- Author
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Koido, Shigeo, Hara, Eiichi, Homma, Sadamu, Namiki, Yoshihisa, Komita, Hideo, Takahara, Akitaka, Nagasaki, Eijiro, Ito, Masaki, Sagawa, Yukiko, Mitsunaga, Makoto, Uchiyama, Kan, Satoh, Kenichi, Arihiro, Seiji, Ohkusa, Toshifumi, Gong, Jianlin, and Tajiri, Hisao
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PANCREATIC cancer , *DENDRITIC cells , *CANCER cells , *BLOOD proteins , *COMPARATIVE studies , *TRANSFORMING growth factors , *INTERLEUKINS , *METASTASIS - Abstract
Abstract: Fetal calf serum (FCS)-independent pancreatic cancer cells were established in plasma protein fraction (PPF)-supplemented medium that is an agent of good manufacturing practice (GMP) grade. Dendritic cells (DCs) were activated with the Toll-like receptor agonist, penicillin-inactivated Streptococcus pyogenes (OK-432) that is also a GMP grade agent. Therefore, sufficient amounts of FCS-independent fusions were successfully generated with decreased potential hazards of FCS. The FCS-independent fusions expressed tumor-associated antigens, HLA-DR, costimulatory molecules, IL-12, and IL-10. Stimulation of T cells with fusions from healthy donors resulted in proliferation of T cells with high expression levels of perforin/granzyme B and IFN-γ and efficient induction of antigen-specific cytotoxic T lymphocytes (CTLs). Selection and expansion of T-cell clones were confirmed by TCR Vβ analysis. However, fusions from patients with metastatic pancreatic cancer induced increased expression levels of TGF-β1 in CD4+ CD25high T cells and low levels of CTLs with decreased IFN-γ production. [Copyright &y& Elsevier]
- Published
- 2010
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