1. ¹Department of Surgery, University of Heidelberg, Heidelberg 69120, Germany
2. ²National Centre for Tumour Diseases, University of Heidelberg, Heidelberg 69120, Germany
3. ³Wound Healing Research Group, BioTec Gründerzentrum, Braunschweig 38124, Germany

Correspondence: Professor A Märten, Department of Surgery, Im Neuenheimer Feld 350, Heidelberg 69120, Germany; E-mail: angela.maerten@med.uni-heidelberg.de

⁴These authors contributed equally to this work.

Received 8 May 2007; Revised 26 June 2007; Accepted 28 June 2007; Published online 31 July 2007.

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 g 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 g 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 17.14.2 months; the median survival being 9.3 months. Two patients are still alive after 31 months. Up to 20 g MALP-2 was well tolerated, and no systemic side effects were noted. The mean survival of 17.1 months is remarkably high.