2005 Fiscal Year Final Research Report Summary
Immunotherapy for prevention of postoperative recurrence in pancreatic cancer using cell therapy and vaccine therapy
| Project/Area Number |
15390397
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Digestive surgery
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| Research Institution | Yamaguchi University |
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Principal Investigator |
OKA Masaaki Yamaguchi University, School of Medicine, Professor, 医学部, 教授 (70144946)
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| Co-Investigator(Kenkyū-buntansha) |
HAZAMA Shoichi Yamaguchi University, Hospital, Assistant Professor, 医学部附属病院, 講師 (50253159)
YOSHINO Shigefumi Yamaguchi University, Faculty of Medicine, Assistant, 医学部, 講師 (60294633)
YAMAMOTO Kotaro Yamaguchi University, Faculty 1 of Medicine, Researcher, 医学部, 非常勤研究員 (50304481)
IIZUKA Norio Yamaguchi University, Faculty 1 of Medicine, Research Associate, 医学部, 助手 (80332807)
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| Project Period (FY) |
2003 – 2005
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| Keywords | Pancreatic Cancer / cell therapy / vaccine therapy / postoperative recurrence |
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| Research Abstract |
(1)Thirty patients with pancreatic cancer were treated by immunotherapy using MUC1-CTL after curative resection. Only 3 patient (10%) had liver recurrence. However, 19 patients (63%) had local recurrence. One year, 2 year, and 3 year survival rate were 83.3%, 32.4%, and 19.9%, respectively. This immunotherapy may prevent liver metastasis after surgery, but can not control local recurrence.
(2)To evaluate safety and immunological responses, we conducted a phase I study of personalized peptide vaccination for pancreatic cancer patients (n=11). Namely, pre-vaccination peripheral blood mononuclear cells were screened for their reactivity in vitro to each of 14 or 16 peptides in HLA-A24(+) or -A2(+) patients, and only the reactive peptides (maximum:4) were vaccinated in vivo. This regimen was generally well tolerated, although inflammatory reactions at the injection site were observed in 7 patients. Delayed-type hypersensitivity to peptides used for vaccination was observed in 7 patients. Increased cellular and humoral immune responses to at least one of peptides used for vaccination were observed in the post-vaccination PBMCs and sera from 4 of 8 patients and 4 of 10 patients tested, respectively. The 6- and 12-month survival rates for patients who received >3 vaccinations (n=10) were 80% and 20%, respectively. Due to tolerability and capability of inducing specific immunity, further development of personalized peptide-based immunotherapy for pancreatic cancer patients is warranted.
(3)We performed MUC1-CTL+personalized peptide-based immunotherapy in 3 patients undergone curative resection for pancreatic cancer. All patients still alive without recurrence.
(4)Fifteen patients with unresectable or recurrence pancreatic cancer were treated with MUC1-CTL+MUC1 peptide stimulated dendritic cells (DC) therapy. One patients had CR and 4 patients had SD. No severe side effects was observed.
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