title: In vivo migration of labeled autologous natural killer cells to liver metastases in patients with colon carcinoma.
abstract: BACKGROUND
  Besides being the effectors of native anti-tumor cytotoxicity, NK cells participate in T-lymphocyte responses by promoting the maturation of dendritic cells (DC). Adherent NK (A-NK) cells constitute a subset of IL-2-stimulated NK cells which show increased expression of integrins and the ability to adhere to solid surface and to migrate, infiltrate, and destroy cancer. A critical issue in therapy of metastatic disease is the optimization of NK cell migration to tumor tissues and their persistence therein. This study compares localization to liver metastases of autologous A-NK cells administered via the systemic (intravenous, i.v.) versus locoregional (intraarterial, i.a.) routes.
  
  
  METHODS
  A-NK cells expanded ex-vivo with IL-2 and labeled with (111)In-oxine were injected i.a. in the liver of three colon carcinoma patients. After 30 days, each patient had a new preparation of (111)In-A-NK cells injected i.v. Migration of these cells to various organs was evaluated by SPET and their differential localization to normal and neoplastic liver was demonstrated after i.v. injection of 99mTc-phytate.
  
  
  RESULTS
  A-NK cells expressed a donor-dependent CD56+ CD16+ CD3- (NK) or CD56+ CD16+ CD3+ (NKT) phenotype. When injected i.v., these cells localized to the lung before being visible in the spleen and liver. By contrast, localization of i.a. injected A-NK cells was virtually confined to the spleen and liver. Binding of A-NK cells to liver neoplastic tissues was observed only after i.a. injections.
  
  
  CONCLUSIONS
  This unique study design demonstrates that A-NK cells adoptively transferred to the liver via the intraarterial route have preferential access and substantial accumulation to the tumor site.
authors.affiliation: Dept of Internal Medicine, University of Turin, Italy. lina.matera@unito.it
authors.forename: Lina
authors.initials: L
authors.lastname: Matera
authors.forename: Alessandra
authors.initials: A
authors.lastname: Galetto
authors.forename: Marilena
authors.initials: M
authors.lastname: Bello
authors.forename: Cinzia
authors.initials: C
authors.lastname: Baiocco
authors.forename: Isabella
authors.initials: I
authors.lastname: Chiappino
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Castellano
authors.forename: Alessandra
authors.initials: A
authors.lastname: Stacchini
authors.forename: Maria A
authors.initials: MA
authors.lastname: Satolli
authors.forename: Michele
authors.initials: M
authors.lastname: Mele
authors.forename: Sergio
authors.initials: S
authors.lastname: Sandrucci
authors.forename: Antonio
authors.initials: A
authors.lastname: Mussa
authors.forename: Gianni
authors.initials: G
authors.lastname: Bisi
authors.forename: Theresa L
authors.initials: TL
authors.lastname: Whiteside