Advanced renal cell carcinoma treated with granulocyte-macrophage colony-stimulating factor gene therapy: a clinical course of the first Japanese experience.
A phase I study of granulocyte-macrophage colony-stimulating factor (GM-CSF) gene-transduced tumor vaccine for patients with metastatic renal cell carcinoma (RCC) was initiated in 1998, as the first cancer gene therapy in Japan. The study is still ongoing, but the first patient is presented here as a case report. The patient was a 60-year-old man with Stage IV CRC with multiple lung metastases. After surgical resection of the tumor, autologous tumor cells were transduced and cultured to produce GM-CSF. The patient received a total of 2.2 x 108 gene-transduced autologous vaccine cells by subcutaneous injection. During the course of vaccination, growth of the largest metastatic mass slowed to some extent; however, multiple new lesions developed. About 1 month after the start of low-dose IL-2 therapy, rapid and remarkable regression in a large lung hilar metastatic mass was noticed. The patient died of progressive disease 7 months after the start of GM-CSF gene therapy. Careful histological examination by autopsy revealed that the responding mass was infiltrated by CD8 positive dominant T lymphocytes, and did not exhibit vasculitis or any other changes associated with active autoimmune disease.
Kawai
Koji
K
Department of Urology, Institute of Clinical Medicine, University of Tsukuba, Ibaraki, Japan. rkawa@md.tsukuba.ac.jp
Tani
Kenzaburo
K
Yamashita
Naohide
N
Tomikawa
Shinji
S
Eriguchi
Masazumi
M
Fujime
Makoto
M
Okumura
Ko
K
Kakizoe
Tadao
T
Clift
Shirley
S
Ando
Dale
D
Mulligan
Richard
R
Yamauchi
Atsusi
A
Noguchi
Masayuki
M
Asano
Shigetaka
S
Akaza
Hideyuki
H
D002292:Carcinoma, Renal Cell / Q000000981:diagnostic imaging / Q000473:pathology / Q000628:therapy*; D017809:Fatal Outcome; D015316:Genetic Therapy; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics*; D006801:Humans; D007564:Japan; D007680:Kidney Neoplasms / Q000000981:diagnostic imaging / Q000473:pathology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D011859:Radiography
D016178:Granulocyte-Macrophage Colony-Stimulating Factor