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


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.
Homma
S
S
Jikei University School of Medicine, Tokyo, Japan. sahya@jikei.ac.jp
Kikuchi
T
T
Ishiji
N
N
Ochiai
K
K
Takeyama
H
H
Saotome
H
H
Sagawa
Y
Y
Hara
E
E
Kufe
D
D
Ryan
J L
JL
Ohno
T
T
Toda
G
G
D002459:Cell Fusion / Q000379:methods; D003713:Dendritic Cells / Q000502:physiology*; D005260:Female; D005334:Fever / Q000209:etiology; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000209:etiology; D007167:Immunotherapy / Q000009:adverse effects / Q000379:methods*; D018664:Interleukin-12 / Q000008:administration & dosage*; D008297:Male; D009369:Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D010865:Pilot Projects; D012867:Skin / Q000276:immunology; D016896:Treatment Outcome; D014407:Tumor Cells, Cultured
D018664:Interleukin-12