Article

Immunotherapy with bovine aortic endothelial cells in subcutaneous and intracerebral glioma models in rats: effects on survival time, tumor growth, and tumor neovascularization.

Department of Neurooncology, Istituto Nazionale Neurologico "C. Besta", 20133, Milan, Italy.
Cancer Immunology and Immunotherapy (impact factor: 3.7). 12/2004; 53(11):955-62. DOI:10.1007/s00262-004-0529-5 pp.955-62
Source: PubMed

ABSTRACT High-grade gliomas are aggressive tumors of the central nervous system characterized by endothelial cell proliferation and a high degree of vascularity. Conventional antitumoral treatments (i.e., surgery, radiotherapy, and chemotherapy) do not achieve satisfactory results (median survival in glioblastoma 12-18 months). It has been suggested that immunotherapy with xenogenic endothelial cells could slow tumor growth rate in a number of tumors in a murine model, but the study did not include gliomas. In experiments performed in our laboratory, vaccination with proliferating bovine aortic endothelium increased survival time in Fischer rats inoculated intracerebrally with 9L. Immunotherapy was also able to reduce the growth of subcutaneously injected 9L gliosarcoma cells in Fischer rats and to decrease microvessel density within the tumors, in the absence of major organ toxicity. Immunoglobulins (Ig) in the sera from vaccinated rats stained bovine aortic endothelium as well as human umbilical vein endothelium in active proliferation. Moreover, immune sera from immunized rats stained microvessels of human malignant glioma specimens and vessels of intracerebrally implanted tumors. Two proteins of MW of 11 and 19 kDa were identified by Western blot as targets of Ig elicited by vaccination. A possible future development is to select peptides/proteins suitable for vaccination in humans, avoiding the biohazards connected with xenogenic whole-cell vaccination.

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Keywords

9L gliosarcoma cells
 
central nervous system
 
Conventional antitumoral treatments
 
decrease microvessel density
 
Fischer rats
 
Fischer rats inoculated intracerebrally
 
glioblastoma 12-18 months
 
human malignant glioma specimens
 
human umbilical vein endothelium
 
Ig elicited
 
immune sera
 
immunized rats stained microvessels
 
major organ toxicity
 
murine model
 
possible future development
 
proliferating bovine aortic endothelium
 
rats stained bovine aortic endothelium
 
satisfactory results
 
survival time
 
Western blot