Intratumoural injection of the toll-like receptor-2/6 agonist 'macrophage-activating lipopeptide-2' in patients with pancreatic carcinoma: a phase I/II trial

Br J Cancer. 2007 Sep 3;97(5):598-604. doi: 10.1038/sj.bjc.6603903. Epub 2007 Jul 31.

Abstract

This phase I/II trial examined safety and efficacy of the toll-like receptor 2/6 agonist MALP-2 in combination with gemcitabine in patients with incompletely resectable pancreas carcinomas. MALP-2 is a toll-like receptor 2/6 agonist, acts as an immunological adjuvant, and has been described recently to prolong survival in a mouse model of an orthotopic, syngeneic pancreas tumour. Male and female patients with incompletely resectable pancreas carcinomas were eligible while those with R0 or R1 resections or with peritoneal carcinosis were excluded. Ten patients were injected intratumourally during surgery with 20-30 microg MALP-2 followed by postoperative chemotherapy. Samples were taken from peripheral blood and wound secretion, and assayed for cell content, cytokine and CRP levels, and NK activity. An MALP-2 dose of 20 microg was well tolerated. Clear signs of local MALP-2 effects were presented by the influx of lymphocytes and monocytes in wound secretions, and abolishment of inhibition of NK activity. The actual mean survival is 17.1+/-4.2 months; the median survival being 9.3 months. Two patients are still alive after 31 months. Up to 20 microg MALP-2 was well tolerated, and no systemic side effects were noted. The mean survival of 17.1 months is remarkably high.

Publication types

  • Clinical Trial, Phase I
  • Clinical Trial, Phase II

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • C-Reactive Protein / metabolism
  • Combined Modality Therapy
  • Cytokines / blood
  • Cytotoxicity, Immunologic / immunology
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / adverse effects
  • Deoxycytidine / analogs & derivatives
  • Female
  • Granzymes / blood
  • Humans
  • Injections, Intralesional
  • Killer Cells, Natural / immunology
  • Lipopeptides
  • Male
  • Middle Aged
  • Myocardial Infarction / chemically induced
  • Oligopeptides / administration & dosage
  • Oligopeptides / adverse effects
  • Pancreatic Neoplasms / blood
  • Pancreatic Neoplasms / drug therapy*
  • Pancreatic Neoplasms / surgery
  • Survival Analysis
  • Time Factors
  • Toll-Like Receptor 2 / agonists*
  • Toll-Like Receptor 6 / agonists*
  • Treatment Outcome

Substances

  • Cytokines
  • Lipopeptides
  • Oligopeptides
  • Toll-Like Receptor 2
  • Toll-Like Receptor 6
  • Deoxycytidine
  • C-Reactive Protein
  • gemcitabine
  • macrophage stimulatory lipopeptide 2
  • Granzymes