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Title: Decreased response rates by the combination of histamine and IL-2 in melphalan-based isolated limb perfusion
Authors: Brunstein, Flavia ×
Hoving, Saske
Aan de Wiel-Ambagtsheer, Gisela
de Bruijn, Ernst
Guetens, Gunther
Eggermont, Alexander M M
Ten Hagen, Timo L M #
Issue Date: Apr-2007
Series Title: Cancer immunology, immunotherapy : CII vol:56 issue:4 pages:573-80
Abstract: Histamine (Hi) combined to melphalan in a rat experimental model of isolated limb perfusion (ILP) for lower limb soft tissue sarcoma, resulted in overall response rates (OR) of 66%. Likewise, ILP with interleukin-2 (IL-2) resulted in OR of 67%, when combined to melphalan, in the same experimental model. In systemic immunotherapy, the combination of IL-2 and Hi has been used for solid tumor treatment based on immunomodulatory effects. In this study, we used our well-established ILP experimental model to evaluate whether the synergistic effect between the two drugs seen in the systemic setting, could further improve response rates in a loco-regional setting. Histological evaluation was done directly and 24 h after ILP. Melphalan uptake by tumor and muscle were measured. Hi and IL-2 together, combined to melphalan in the ILP led to OR of only 28%. Histology of tumors demonstrated partial loss of Hi-induced hemorrhagic effect when IL-2 was present. Melphalan accumulation in the tumor when both Hi and IL-2 were added (3.1-fold) was very similar to accumulation with Hi only (2.8-fold), or IL-2 only (3.5-fold) combined to melphalan. In vitro there was no synergy between the drugs. In conclusion there was a negative synergistic effect between IL-2 and Hi in the regional setting.
URI: 
ISSN: 0340-7004
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Experimental Oncology
Department of Oncology - miscellaneous
× corresponding author
# (joint) last author

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