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J Transl Med. 2015 Mar 14;13:90. doi: 10.1186/s12967-015-0441-0.

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

Author information

1
Batu Biologics Inc, San Diego, 9255 Towne Centre Drive, Suite 450, San Diego, CA, 92121, USA. thomas.ichim@gmail.com.
2
Department of Endocrinology, The Affiliated Zhongshan Hospital of Dalian University, Dalian, 116001, China. shuanglqw1109@163.com.
3
Batu Biologics Inc, San Diego, 9255 Towne Centre Drive, Suite 450, San Diego, CA, 92121, USA. hongma2008@gmail.com.
4
Nova Southeastern University, Fort Lauderdale, Florida, USA. yy21@nova.edu.
5
Batu Biologics Inc, San Diego, 9255 Towne Centre Drive, Suite 450, San Diego, CA, 92121, USA. julszymanski@gmail.com.
6
Department of Surgery, University of Utah, Salt Lake City, Utah. amit.patel@hsc.utah.edu.
7
Department of Neurosciences, University of California San Diego, 9500 Gilman Dr., MSC 0752, La Jolla, San Diego, CA, 92093-0752, USA. skesari@ucsd.edu.
8
Translational Neuro-Oncology Laboratories, Moores Cancer Center, University of California San Diego, 3855 Health Sciences Dr., MSC 0819, La Jolla, San Diego, CA, 92093-0819, USA. skesari@ucsd.edu.
9
Department of Immunology, University of Western Ontario, London, Ontario, Canada. ameeek@gmail.com.
10
Batu Biologics Inc, San Diego, 9255 Towne Centre Drive, Suite 450, San Diego, CA, 92121, USA. samuel.wagner@batubiologics.com.

Abstract

BACKGROUND:

While 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.

METHOD:

Placenta-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.

RESULTS:

ValloVax™ 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.

CONCLUSION:

Given 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.

PMID:
25889119
PMCID:
PMC4363400
DOI:
10.1186/s12967-015-0441-0
[Indexed for MEDLINE]
Free PMC Article

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