Cancer immunotherapy by fusions of dendritic and tumour cells and rh-IL-12

被引:34
作者
Homma, S
Kikuchi, T
Ishiji, N
Ochiai, K
Takeyama, H
Saotome, H
Sagawa, Y
Hara, E
Kufe, D
Ryan, JL
Ohno, T
Toda, G
机构
[1] Jikei Univ, Sch Med, Inst DNA Med, Dept Oncol,Minato Ku, Tokyo 1058461, Japan
[2] Jikei Univ, Sch Med, Inst DNA Med, Dept Clin Data Bank, Tokyo 1058461, Japan
[3] Jikei Univ, Sch Med, Dept Internal Med, Div Gastroenterol & Hepatol, Tokyo 1058461, Japan
[4] Jikei Univ, Sch Med, Dept Neurosurg, Tokyo 1058461, Japan
[5] Jikei Univ, Sch Med, Dept Dermatol, Tokyo 1058461, Japan
[6] Jikei Univ, Sch Med, Dept Gynecol, Tokyo 1058461, Japan
[7] Jikei Univ, Sch Med, Dept Surg, Tokyo 1058461, Japan
[8] AHP Serv Japan Co Ltd, Wyeth Res Dept, Tokyo, Japan
[9] Saitama Canc Ctr, Res Inst Clin Oncol, Cell Therapy Lab, Kita Adachi, Japan
[10] Dana Farber Canc Inst, Boston, MA 02115 USA
[11] Wyeth Pharmaceut, Res & Dev, Expt Med, Cambridge, MA USA
关键词
cell fusion; dendritic cell; IL-12; immunotherapy; tumour vaccine;
D O I
10.1111/j.1365-2362.2005.01494.x
中图分类号
R5 [内科学];
学科分类号
1002 [临床医学]; 100201 [内科学];
摘要
Background Vaccination with fusion cells (FCs) comprising dendritic cells and tumour cells as well as administration of interleukin-12 (IL-12) showed a significant therapeutic effect against established tumours in mouse experimental models. We conducted immunotherapy against various malignant tumours using the FCs and rhIL-12, and investigated the safety and efficacy of the therapy. Materials and methods Patients' DCs were mixed with autologous irradiated tumour cells and treated with 50% polyethylene glycol to generate FCs. The FCs were inoculated intradermally, and then 30 ng kg(-1) of rhIL-12 was injected at the same sites 2 and 6 days later. This process was carried out as one cycle, and three of these cycles were repeated at 1-week intervals to comprise one course. After completing the course, its safety and therapeutic effects were estimated. Results The most frequently observed adverse event was fever, observed in 26% of patients in the first cycle. Decrease in white blood cell and an increase in serum ALT were observed in 28% and 25%, respectively. Three out of 12 patients with a malignant brain tumour (25%) achieved a partial response (PR), but other patients with a malignant tumour showed no regression of their tumours. Thirteen out of 16 patients with a brain tumour (81%) showed cutaneous delayed hypersensitivity responses. However, only one of 16 patients (6%) with a malignant tumour other than a brain tumour developed such responses. Conclusions Immunotherapy using a FC vaccine and rhIL-12 induced no serious adverse reactions, and provided good therapeutic responses in some of the patients with a brain tumour.
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收藏
页码:279 / 286
页数:8
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