1997 Fiscal Year Final Research Report Summary
Development of novel adoptive immunotherapy of malignant effusions using tumor cells genetically engineered to secrete interleukin-2
| Project/Area Number |
07457254
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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 |
General surgery
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| Research Institution | HIROSHIMA UNIVERSITY |
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Principal Investigator |
TOGE Tetsuya Research Institute for Radiation Biology and Medicine, Hiroshima University, Professor, 原爆放射能医学研究所, 教授 (40034657)
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| Co-Investigator(Kenkyū-buntansha) |
MIYAHARA Eiji Hiroshima University Medical Hospital, Medical stuff, 医学部・附属病院, 医員
YAMAGUCHI Yoshiyuki Research Institute for Radiation Biology and Medicine, Hiroshima University, Ass, 原爆放射能医学研究所, 講師 (10230377)
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| Project Period (FY) |
1995 – 1997
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| Keywords | lymphocyte therapy / malignant effusion / gene transfection / cytotoxic T lymphocytes / IL-2 |
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| Research Abstract |
Malignant effusion is one of the most frequent complications in patients with fatal cancer and the establishment of effective treatment for malignant effusions is recently focuced in the world. We have attempted to develop the novel adoptive immunotherapy of malignant effusions using lymphocytes stimulated with tumor cells genetically engineered to secrete interleukin (IL)-2.
First, tumor cell lines (2 gastric, 2 colon and 1 pancreatic cancer cell lines) were established and retrovirally transduced with human IL-2 gene. Transgene was detected by mRNA analysis and IL-2 secretion was confirmed by ELISA and bioassay specific IL-2. Second, these tumor cells were inactivated with mytomicin C and subjected for in vitro stimulation of patients' lymphocytes. The lymphocytes were further cultured with solid phase-CD3/IL-2 system which could make 1,000-fold expansion. The lymphocytes had a significantly potent cytotoxicity againt tumor cells. Finally, 3 patients with malignant effusion were treated with this system in safe and clinical efficacy was obtained in 2 patients.
It is suggested that adoptive immunotherapy using lymphocytes stimulated with tumor cells genetically engineered to secrete interleukin (IL) -2 may effective for treatment of malignant effusions. Further experiences are warranted to make sure the efficacy of this novel treatment modality.
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