Morphological and Immunohistochemical Description of a Splenic Haemangioma in a Captive European Wolf (Canis lupus lupus) and a Review of the Current Literature.

Neoplastic diseases are rarely described in wild carnivores; only a few reports have been published on this topic. Here, we describe the histological and immunohistochemical features of a haemangioma in the spleen of a grey wolf (Canis lupus lupus) and we compare the results with the dog (Canis lupus familiaris). Additionally, we list the different publications found in the literature with neoplastic lesions in wolves. Our results show similar immunohistochemical features to dogs, in which neoplastic cells express Vimentin, von Willebrand factor, alpha smooth muscle actin antibody, vascular endothelial growth factor C and low vascular endothelial growth factor receptor 3. Toluidine blue special stain shows moderated increased numbers of mast cells infiltrating the tumor, a feature observed in benign vascular tumors in domestic dogs, but not in the malignant counterparts. To our knowledge, this is the first article describing the gross, histological and immunohistochemical features of a splenic haemangioma in a wolf.

Comparative evaluation of bolus and fractionated administration modalities for two antibody-cytokine fusions in immunocompetent tumor-bearing mice.

Antibody-cytokine fusion proteins are being considered as biopharmaceuticals for cancer immunotherapy. Tumor-homing cytokine fusions typically display an improved therapeutic activity compared to the corresponding unmodified cytokine products, but toxicity profiles at equivalent doses are similar, since side effects are mainly driven by the cytokine concentration in blood. In order to explore avenues to harness the therapeutic potential of antibody-cytokine fusions while decreasing potential toxicity, we compared bolus and fractionated administration modalities for two tumor-targeting antibody-cytokine fusion proteins based on human interleukin-2 (IL2) and murine tumor necrosis factor (TNF) (i.e., L19-hIL2 and L19-mTNF) in two murine immunocompetent mouse models of cancer (F9 and C51). A comparative quantitative biodistribution analysis with radio-labeled protein preparations revealed that a fractionated administration of L19-hIL2 could deliver comparable product doses to the tumor with decreased product concentration in blood and normal organs, compared to bolus injection. By contrast, L19-mTNF (a product that causes a selective vascular shutdown in the tumor) accumulated most efficiently after bolus injection. Fractionated schedules allowed the safe administration of a cumulative dose of L19-mTNF, which was 2.5-times higher than the lethal dose for bolus injection. Dose fractionation led to a prolonged tumor growth inhibition for F9 teratocarcinomas, but not for C51 colorectal tumors, which responded best to bolus injection. Thus, dose fractionation may have different outcomes for the same antibody-cytokine product in different biological contexts.