title: Enhancement of antitumor radiation efficacy and consistent induction of the abscopal effect in mice by ECI301, an active variant of macrophage inflammatory protein-1alpha.
abstract: OBJECTIVE
  We studied whether i.v. administration of a chemokine after local tumor site irradiation could prevent remaining, as well as distant, nonirradiated tumor cell growth by leukocyte recruitment.
  
  
  METHODS
  Tumors were implanted s.c. in the right or both flanks. After local irradiation at the right flank, ECI301, a human macrophage inflammatory protein-1alpha variant was injected i.v. Tumor volumes were measured every 3 days after treatment.
  
  
  RESULTS
  In Colon26 adenocarcinoma-bearing BALB/c mice, repeated daily administration (over 3-5 consecutive days) of 2 mug per mouse ECI301 after local irradiation of 6 Gy prolonged survival without significant toxicity, and in about half of the treated mice, the tumor was completely eradicated. Three weekly administrations of ECI301 after local irradiation also led to significant, although less effective, antitumor radiation efficacy. ECI301 also inhibited growth of other syngenic tumor grafts, including MethA fibrosarcoma (BALB/c) and Lewis lung carcinoma (C57BL/6). Importantly, tumor growth at the nonirradiated site was inhibited, indicating that ECI301 potentiated the abscopal effect of radiation. This abscopal effect observed in BALB/c and C57BL/6 mice was tumor-type independent. Leukocyte depletion studies suggest that CD8+ and CD4+ lymphocytes and NK1.1 cells were involved.
  
  
  CONCLUSIONS
  Marked inhibition of tumor growth at the irradiated site, with complete tumor eradication and consistent induction of the abscopal effect, was potentiated by i.v. administration of ECI301. The results of this study may offer a new concept for cancer therapy, namely chemokine administration after local irradiation, leading to development of novel therapeutics for the treatment of advanced metastatic cancer.
authors.affiliation: Department of Radiology, University of Tokyo Hospital, Tokyo, Japan.
authors.forename: Kenshiro
authors.initials: K
authors.lastname: Shiraishi
authors.forename: Yoshiro
authors.initials: Y
authors.lastname: Ishiwata
authors.forename: Keiichi
authors.initials: K
authors.lastname: Nakagawa
authors.forename: Shoji
authors.initials: S
authors.lastname: Yokochi
authors.forename: Chiho
authors.initials: C
authors.lastname: Taruki
authors.forename: Teruo
authors.initials: T
authors.lastname: Akuta
authors.forename: Kuni
authors.initials: K
authors.lastname: Ohtomo
authors.forename: Kouji
authors.initials: K
authors.lastname: Matsushima
authors.forename: Takuya
authors.initials: T
authors.lastname: Tamatani
authors.forename: Shiro
authors.initials: S
authors.lastname: Kanegasaki
mesh_terms: D000818:Animals; D054405:Chemokine CCL3 / Q000008:administration & dosage*; D003131:Combined Modality Therapy; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000276:immunology* / Q000532:radiotherapy*; D011878:Radiotherapy
chemical_list: D054405:Chemokine CCL3