title: Flavone acetic acid enhances accumulation of IL-2 activated NK cells within established metastases.
abstract: Flavone acetic acid, an agent which has been implicated in both tumor vasculature collapse and NK cell activations, has been tested recently as a potential anti-cancer chemotherapeutic agent. We have tested this agent in combination with adoptive immunotherapy using IL-2 activated natural killer (A-NK) cells in a metastatic B16 melanoma model in C57BL/6 mice. By using rhodamine-labeled A-NK cells we have been able to quantitate both the number of A-NK cells that localize within each tumor section and the percentage of the tumor area occupied by A-NK cells. This has been accomplished using an image analysis system. Flavone acetic acid (200 mg/kg, i.p.) given one day prior to the injection of A-NK cells increased the area of the tumor occupied by A-NK cells and the area of individual A-NK cells approximately 2-fold; however, it did not appear to increase the number of A-NK cells per tumor cross-section. Nevertheless, this increase did not lead to any significant change in the therapeutic efficacy of A-NK cell adoptive immunotherapy. Our studies therefore suggest that mere enhancement of A-NK cell recruitment into tumor metastases does not necessarily translate into enhanced metastatic therapeutic efficacy. Moreover, this method may be a useful tool for pre-screening of compounds which enhance the accumulation of adoptively transferred cells into tumor metastases prior to in vivo screening for therapeutic efficacy.
authors.affiliation: University of Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine, PA 15213, USA.
authors.forename: R P
authors.initials: RP
authors.lastname: Kitson
authors.forename: M
authors.initials: M
authors.lastname: Ohashi
authors.forename: K W
authors.initials: KW
authors.lastname: Brunson
authors.forename: R H
authors.initials: RH
authors.lastname: Goldfarb
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D004317:Doxorubicin / Q000494:pharmacology; D005260:Female; D005419:Flavonoids / Q000494:pharmacology*; D007091:Image Processing, Computer-Assisted; D016219:Immunotherapy, Adoptive; D015979:Killer Cells, Lymphokine-Activated / Q000502:physiology*; D008175:Lung Neoplasms / Q000276:immunology* / Q000556:secondary; D051379:Mice; D008810:Mice, Inbred C57BL; D008856:Microscopy, Fluorescence; D009368:Neoplasm Transplantation; D014407:Tumor Cells, Cultured
chemical_list: D000276:Adjuvants, Immunologic; D000970:Antineoplastic Agents; D005419:Flavonoids; D004317:Doxorubicin; C049328:flavone acetic acid