Delivery of methoxymorpholinyl doxorubicin by interleukin 2-activated NK cells: Effect in mice bearing hepatic metastases

L. Quintieri, A. Rosato, N. Amboldi, C. Vizler, D. Ballinari, P. Zanovello, D. Collavo

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

The possibility of using interleukin 2 (IL-2)-activated natural killer cells (A-NK) to carry methoxymorpholinyl doxorubicin (MMDX; PNU 152243) to liver-infiltrating tumours was explored in mice bearing 2-day established M5076 reticulum cell sarcoma hepatic metastases. In vitro, MMDX was 5.5-fold more potent than doxorubicin against M5076 tumour cells. MMDX uptake by A-NK cells correlated linearly with drug concentration in the incubation medium [correlation coefficient (r) = 0.999]; furthermore, as MMDX incorporation was readily reproducible in different experiments, the amount of drug delivered by A-NK cells could be modulated. In vivo experiments showed that intravenous (i.v.) injection of MMDX-loaded A-NK cells exerted a greater therapeutic effect than equivalent or even higher doses of free drug. The increase in lifespan (ILS) following A-NK cell delivery of 53 μg kg-1 MMDX, a dosage that is ineffective when administered in free form, was similar to that observed in response to 92 μg kg-1 free drug, a dosage close to the 10% lethal dose (ILS 42% vs, 38% respectively). These results correlated with pharmacokinetic studies showing that MMDX encapsulation in A-NK cells strongly modifies its organ distribution and targets it to tissues in which IL-2 activated lymphocytes are preferentially entrapped after i.v. injection.

Original languageEnglish
Pages (from-to)1067-1073
Number of pages7
JournalBritish journal of cancer
Volume79
Issue number7-8
DOIs
Publication statusPublished - Feb 28 1999

Keywords

  • A-NK cell
  • Drug delivery
  • Liver metastases
  • Methoxymorpholinyl doxorubicin

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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