title: Advanced renal cell carcinoma treated with granulocyte-macrophage colony-stimulating factor gene therapy: a clinical course of the first Japanese experience.
abstract: 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.
authors.affiliation: Department of Urology, Institute of Clinical Medicine, University of Tsukuba, Ibaraki, Japan. rkawa@md.tsukuba.ac.jp
authors.forename: Koji
authors.initials: K
authors.lastname: Kawai
authors.forename: Kenzaburo
authors.initials: K
authors.lastname: Tani
authors.forename: Naohide
authors.initials: N
authors.lastname: Yamashita
authors.forename: Shinji
authors.initials: S
authors.lastname: Tomikawa
authors.forename: Masazumi
authors.initials: M
authors.lastname: Eriguchi
authors.forename: Makoto
authors.initials: M
authors.lastname: Fujime
authors.forename: Ko
authors.initials: K
authors.lastname: Okumura
authors.forename: Tadao
authors.initials: T
authors.lastname: Kakizoe
authors.forename: Shirley
authors.initials: S
authors.lastname: Clift
authors.forename: Dale
authors.initials: D
authors.lastname: Ando
authors.forename: Richard
authors.initials: R
authors.lastname: Mulligan
authors.forename: Atsusi
authors.initials: A
authors.lastname: Yamauchi
authors.forename: Masayuki
authors.initials: M
authors.lastname: Noguchi
authors.forename: Shigetaka
authors.initials: S
authors.lastname: Asano
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Akaza
mesh_terms: 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
chemical_list: D016178:Granulocyte-Macrophage Colony-Stimulating Factor