title: Effects of stimulating interleukin -2/anti- interleukin -2 antibody complexes on renal cell carcinoma.
abstract: BACKGROUND
  Current therapies for advanced renal cell carcinoma (RCC) have low cure rates or significant side effects. It has been reported that complexes composed of interleukin (IL)-2 and stimulating anti-IL-2 antibody (IL-2C) suppress malignant melanoma growth. We investigated whether it could have similar effects on RCC.
  
  
  METHODS
  A syngeneic RCC model was established by subcutaneously injecting RENCA cells into BALB/c mice, which were administered IL-2C or phosphate-buffered saline every other day for 4 weeks. RCC size was measured serially, and its weight was assessed 4 weeks after RENCA injection. Immune cell infiltration into RCC lesions and spleen was assessed by flow cytometry and immunohistochemistry.
  
  
  RESULTS
  IL-2C treatment increased the numbers of CD8(+) memory T and natural killer (NK) cells in healthy BALB/c mice (P < 0.01). In the spleen of RCC mice, IL-2C treatment also increased the number of CD8(+) memory T, NK cells, and macrophages as compared to PBS-treated controls (P < 0.01). The number of interferon-γ- and IL-10-producing splenocytes increased and decreased, respectively after 4 weeks in the IL-2C-treated mice (P < 0.01). Tumor-infiltrating immune cells including CD4(+) T, CD8(+) T, NK cells as well as macrophages were increased in IL-2C-treated mice than controls (P < 0.05). Pulmonary edema, the most serious side effect of IL-2 therapy, was not exacerbated by IL-2C treatment. However, IL-2C had insignificant inhibitory effect on RCC growth (P = 0.1756).
  
  
  CONCLUSIONS
  IL-2C enhanced immune response without significant side effects; however, this activity was not sufficient to inhibit RCC growth in a syngeneic, murine model.
authors.affiliation: Transplantation Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea. truehan1@empas.com.
authors.forename: Kyu-Hyun
authors.initials: KH
authors.lastname: Han
authors.affiliation: Nephrology clinic, Center for Clinical Specialty, National Cancer Center, Seoul, Republic of Korea. carnagekim@nate.com.
authors.forename: Ki Won
authors.initials: KW
authors.lastname: Kim
authors.affiliation: Transplantation Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea. jjyanpharm@gmail.com.
authors.forename: Ji-Jing
authors.initials: JJ
authors.lastname: Yan
authors.affiliation: Transplantation Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea. jaeghi@gmail.com.
authors.forename: Jae-Ghi
authors.initials: JG
authors.lastname: Lee
authors.affiliation: Transplantation Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea. vita77@snu.ac.kr.
authors.forename: Eun Mi
authors.initials: EM
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea. myeun81@hanmail.net.
authors.forename: Miyeon
authors.initials: M
authors.lastname: Han
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea. ejsquare@hanmail.net.
authors.forename: Eun Jin
authors.initials: EJ
authors.lastname: Cho
authors.affiliation: Transplantation Center, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 110-744, Republic of Korea. kangseong@empas.com.
authors.forename: Seong Sik
authors.initials: SS
authors.lastname: Kang
authors.affiliation: Transplantation Center, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 110-744, Republic of Korea. ihyejin01@naver.com.
authors.forename: Hye Jin
authors.initials: HJ
authors.lastname: Lim
authors.affiliation: Transplantation Center, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 110-744, Republic of Korea. marvin77@empal.com.
authors.forename: Tai Yeon
authors.initials: TY
authors.lastname: Koo
authors.affiliation: Transplantation Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea. curie@snu.ac.kr.|Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea. curie@snu.ac.kr.|Transplantation Center, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 110-744, Republic of Korea. curie@snu.ac.kr.
authors.forename: Curie
authors.initials: C
authors.lastname: Ahn
authors.affiliation: Transplantation Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea. jcyjs@dreamwiz.com.|Transplantation Center, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 110-744, Republic of Korea. jcyjs@dreamwiz.com.
authors.forename: Jaeseok
authors.initials: J
authors.lastname: Yang
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D000936:Antigen-Antibody Complex / Q000494:pharmacology*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D002292:Carcinoma, Renal Cell / Q000276:immunology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D058501:Enzyme-Linked Immunospot Assay; D007376:Interleukin-2 / Q000276:immunology / Q000494:pharmacology*; D007680:Kidney Neoplasms / Q000276:immunology*; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000276:immunology; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex; D007376:Interleukin-2