Induction of tumor inhibitory anti-angiogenic response through immunization with interferon Gamma primed placental endothelial cells: ValloVax™Report as inadecuate




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Journal of Translational Medicine

, 13:90

First Online: 14 March 2015Received: 27 January 2015Accepted: 18 February 2015DOI: 10.1186-s12967-015-0441-0

Cite this article as: Ichim, T.E., Li, S., Ma, H. et al. J Transl Med 2015 13: 90. doi:10.1186-s12967-015-0441-0

Abstract

BackgroundWhile the concept of angiogenesis blockade as a therapeutic intervention for cancer has been repeatedly demonstrated, the full promise of this approach has yet to be realized. Specifically, drugs such as VEGF-blocking antibodies or kinase inhibitors suffer from the drawbacks of resistance development, as well as off-target toxicities. Previous studies have demonstrated feasibility of specifically inducing immunity towards tumor endothelium without consequences of systemic autoimmunity in both animal models and clinical settings.

MethodPlacenta-derived endothelial cells were isolated and pretreated with interferon gamma to enhance immunogenicity. Syngeneic mice received subcutaneous administration of B16 melanoma, 4 T1 mammary carcinoma, and Lewis Lung Carcinoma LLC, followed by administration of control saline, control placental endothelial cells, and interferon gamma primed endothelial cells ValloVax™. Tumor volume was quantified. An LLC metastasis model was also established and treated under similar conditions. Furthermore, a safety analysis in non-tumor bearing mice bracketing the proposed clinical dose was conducted.

ResultsValloVax™ immunization led to significant reduction of tumor growth and metastasis as compared to administration of non-treated placental endothelial cells. Mitotic inactivation by formalin fixation or irradiation preserved tumor inhibitory activity. Twenty-eight day evaluation of healthy male and female mice immunized with ValloVax™ resulted in no abnormalities or organ toxicities.

ConclusionGiven the established rationale behind the potential therapeutic benefit of inhibiting tumor angiogenesis as a treatment for cancer, immunization against a variety of endothelial cell antigens may produce the best clinical response, enhancing efficacy and reducing the likelihood of the development of treatment resistance. These data support the clinical evaluation of irradiated ValloVax™ as an anti-angiogenic cancer vaccine.

Thomas E Ichim and Shuang Li contributed equally to this work.

Electronic supplementary materialThe online version of this article doi:10.1186-s12967-015-0441-0 contains supplementary material, which is available to authorized users.

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Author: Thomas E Ichim - Shuang Li - Hong Ma - Yuliya V Yurova - Julia S Szymanski - Amit N Patel - Santosh Kesari - Wei-Ping 

Source: https://link.springer.com/







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