Immunotherapy with bovine aortic endothelial cells in subcutaneous and intracerebral glioma models in rats: effects on survival time, tumor growth, and tumor neovascularization.
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.
Article: Cancer vaccines.[show abstract] [hide abstract]
ABSTRACT: The term cancer vaccines encompasses 2 different types of vaccines. Prophylactic vaccines block infection by viruses that can alter host DNA and result in cancer. The hepatitis B vaccine and the human papillomavirus vaccines are examples of prophylactic vaccines that can prevent cancer from developing. More recently, therapeutic vaccines have been developed and used as adjunctive therapy in patients who have already been diagnosed with cancer. Therapeutic vaccines stimulate the host's immune system to recognize cancer cells as foreign and to attack them. Most of the therapeutic vaccines being studied are used in combination with other forms of cancer therapy.Primary care 12/2011; 38(4):703-15, viii-ix. · 0.81 Impact Factor
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ABSTRACT: Targeting angiogenesis represents a new strategy for the development of anticancer therapies. New targets derived from proliferating endothelial cells may be useful in developing anticancer drugs that prolong or stabilize the progression of tumors with minimal systemic toxicities. These drugs may also be used as novel imaging and radiommunotherapeutic agents in cancer therapy. In this review, the mechanisms and control of angiogenesis are discussed. Genetic and proteomic approaches to defining new potential targets on tumor vasculature are then summarized, followed by discussion of possible antiangiogenic treatments that may be derived from these targets and current clinical trials. Such strategies involve the use of endogenous antiangiogenic agents, chemotherapy, gene therapy, antiangiogenic radioligands, immunotherapy, and endothelial cell-based therapies. The potential biologic end points, toxicities, and resistance mechanisms to antiangiogenic agents must be considered as these therapies enter clinical trials.Journal of Clinical Oncology 10/2002; 20(18):3906-27. · 18.04 Impact Factor
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ABSTRACT: An attractive strategy for the therapy of carcinomas and other solid tumors would be to target cytotoxic agents or host immune effectors to the endothelial cells of the tumor vasculature rather than to the tumor cells themselves. The key advantage of this approach is that the endothelial cells are freely accessible through the blood whereas the tumor cells are, for the most part, inaccessible. Also, endothelial cells are similar in different tumors, making it feasible to develop a single reagent for treating numerous types of cancer. In this chapter, we review progress in this "vascular targeting" approach, from the validation of the concept in a mouse model to the characterization of the TEC-11 antibody against endoglin, an endothelial cell proliferation marker that is upregulated on endothelial cells in miscellaneous human solid tumors. In addition, we review other tumor endothelial cell markers that are candidates for vascular targeting in man.Breast Cancer Research and Treatment 02/1995; 36(2):237-51. · 4.47 Impact Factor