Preparation of activated dendritic cells capable of priming tumor-specific cytotoxic T lymphocytes in patients with metastatic cancer using penicillin-killed streptococcus pyogenes (OK432) and anti-CD40 antibody
| Project/Area Number |
17591475
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Thoracic surgery
|
|---|
| Research Institution | Kagawa University |
|---|
Principal Investigator |
KONTANI Keiichi Kagawa University, Faculty of Medicine, Lecturer, 医学部附属病院, 講師 (90314153)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
YOKOMISE Hiroyasu Kagawa University, Faculty of Medicine, Professor, 医学部, 教授 (80231728)
HUANG Cheng-long Kagawa University, Faculty of Medicine, Assistant Professor, 医学部, 助教授 (10271511)
YAMAUCHI Akira Kagawa University, Faculty of Medicine, Professor, 医学部, 教授 (00291427)
木原 実 香川大学, 医学部附属病院, 助手 (50322269)
|
|---|
| Project Period (FY) |
2005 – 2006
|
| Project Status |
Completed (Fiscal Year 2006)
|
| Budget Amount *help |
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2006: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2005: ¥2,000,000 (Direct Cost: ¥2,000,000)
|
|---|
| Keywords | cancer vaccine / immunotherapy / dendritic cell / tumor antigen / cytokine / 外科 / 樹状制帽 / 細胞ワクチン / 乳癌・肺癌 |
|---|
| Research Abstract |
In order to achieve sufficient therapeutic potency, it has been proposed that vaccine therapy with dendritic cells needs to be combined with manipulation of immunological checkpoints, such as inhibition of regulatory T cells and blockade of negative signals, and enhancement of T cell trafficking to tumor sites. In the combinatorial cancer immunotherapy, use of matured/activated dendritic cells (DCs) with more potent antigen presenting capacity seems to be essential for eliciting anti-tumor immune responses. We herein established an ex vivo induction strategy for activated DCs capable of eliciting efficient tumor antigen-specific cytotoxic T lymphocytes (CTLs) from patients with metastatic cancer as well as healthy donors. Immature DCs were matured by 48 h-culture in the presence of anti-CD40 antibody and penicillin-killed streptococcus pyogenes (0K432). Supplementation with both anti-CD40 antibody and OK432 resulted in induction of activated DCs with higher surface expression of CD80, CD83, CD86 and major histocompatibility complex (MHC) class II antigens, compared with other mature DCs that were induced by the combination of anti-CD40 with tumor necrosis factor-alpha (TNF-a) or lipopolysaccharide (LPS). In analysis of the produced cytokine profiles, the activated DCs produced the highest T-helper 1 (Th1)-type cytokines for at least 72 h. Furthermore, the activated DCs, pulsed with tumor-associated antigen (TAA) peptide, elicited in vitro tumor-specific CTLs, but DCs prepared with other combinations did not in cancer patients. Therefore, we suggest that the activated DCs shown here might be used as a basic element for the combinatorial cancer immunotherapy.
|
Report
(3 results)
Research Products
(8 results)
