2002 Fiscal Year Final Research Report Summary
CLINICAL STUDY OF LOCOREGIONAL ADOPTIVE CELLULAR IMMUNOTHERAPY FOR THE CANCER OF DIGESTIVE TRACT
| Project/Area Number |
12671283
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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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 | KURUME UNIVERSITY |
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Principal Investigator |
TOH Uhi KURUME UNIV. SCHL. OF MEDICINE, ASSIT. PROF., 医学部, 助手 (60268901)
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| Co-Investigator(Kenkyū-buntansha) |
SUEYOSHI Susumu KURUME UNIV. SCHL. OF MEDICINE, ASSIT. PROF., 医学部, 講師 (30235840)
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| Project Period (FY) |
2000 – 2002
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| Keywords | CANCER IMMUNOTHERAPY / AUTOLOUGUS TUMOR CELL-STIMULATED T LYMPHOCYTE / LOCOREGIONAL ADMINISTRATION / PHASE I / II STUDY / REGULATORY T CELL / PROTEASOME INHIBITOR / CYTOKINE / サイトカイン |
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| Research Abstract |
In first 2 years, to develop a novel tumor-specific adoptive cellular immunotherapy, we conducted a phase I/II clinical trial for patients with refractory advanced or recurrent esophageal cancer. The tumor cell-stimulated T cells (AuTL) were propagated ex vivo by a mixed culture with autologous tumor cell and peripheral blood lymphocytes. In 5 of 11 cases (45%), the AuTLs showed a specific cytotoxicity against autologous tumor cell and other tumor cells lines in an HLA- class I molecular restricted manner tested by ^<51>Cr release assay and IFN-g production assay. These AuTLs were administrated into the tumor locoregionally by repeated direct or endoscopic injections. The clinical response was observed with 1 CR, 3 PRs, 2 SDs and 5 PDs and adverse events were all tolerable. This study also suggested CTL activity in the administrated cells and percentages of CD16^+ cells in the peripheral blood might be laboratory markers for prediction of clinical response. In last year, in order to investigate a new modulator to enhance effects of this immunotherapy, we focused on a synergistic effect in inducing human tumor cell apoptosis between the proteasome inhibitor (PS-341) in combination with the cytotoxic protein TRAIL. High doses of PS-341 alone were toxic to the most human tumor cell lines. However, in presence of TRAIL the apoptosis would be greatly enhanced by intermediate doses of PS-341. Proteasome inhibitor might be a novel modulator for cancer immunotherapy.
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Research Products
(12 results)
