Dendritic/pancreatic carcinoma fusions for clinical use: Comparative functional analysis of healthy- versus patient-derived fusions.
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| 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-gamma and efficient induction of antigen-specific cytotoxic T lymphocytes (CTLs). Selection and expansion of T-cell clones were confirmed by TCR Vbeta analysis. However, fusions from patients with metastatic pancreatic cancer induced increased expression levels of TGF-beta1 in CD4+ CD25high T cells and low levels of CTLs with decreased IFN-gamma production.
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| Authors | Shigeo Koido, Eiichi Hara, Sadamu Homma, Yoshihisa Namiki, Hideo Komita, Akitaka Takahara, Eijiro Nagasaki, Masaki Ito, Yukiko Sagawa, Makoto Mitsunaga, Kan Uchiyama, Kenichi Satoh, Seiji Arihiro, Toshifumi Ohkusa, Jianlin Gong, Hisao Tajiri |
| Journal | Clinical immunology (Orlando, Fla.) (Clin Immunol) Vol. 135 Issue 3 Pg. 384-400 (Jun 2010) ISSN: 1521-7035 [Electronic] United States |
| PMID | 20226739 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't) |
| Copyright | Copyright 2010 Elsevier Inc. All rights reserved. |
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