alexa Development of inCVAX, In situ Cancer Vaccine, and Its Immune Response in Mice with Hepatocellular Cancer | OMICS International
ISSN: 2155-9899

Journal of Clinical & Cellular Immunology
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Research Article

Development of inCVAX, In situ Cancer Vaccine, and Its Immune Response in Mice with Hepatocellular Cancer

Xiaoqiang Qi1,2, Samuel SK Lam3, Dai Liu1,2, Dae Young Kim4, Lixin Ma5, Lu Alleruzzo3, Wei Chen6, Tomas Hode3, Carolyn J Henry7, Jussuf Kaifi1,2, Eric T Kimchi1,2, Guangfu Li1,2* and Kevin F Staveley-O’Carroll1,2,8*

1Department of Surgery, University of Missouri, Columbia, MO 65212, USA

2Ellis Fischel Cancer Center, University of Missouri, Columbia, MO 65212, USA

3Immunophotonics Inc., 4320 Forest Park Avenue #303, St. Louis, Missouri 63108, USA

4Veterinary Medical Diagnostic Laboratory, College of Veterinary Medicine, University of Missouri, Columbia, MO 65212, USA

5Department of Radiology, University of Missouri, Columbia, MO 65212; Harry S. Truman Memorial VA Hospital Biomolecular Imaging Center, USA

6Veterinary Medical and Surgery, College of Veterinary Medicine, University of Missouri, Columbia, MO 65212, USA

7Department of Molecular Microbiology and Immunology, University of Missouri, Columbia, MO 65212, USA

8Department of Molecular Microbiology and Immunology, University of Missouri, Columbia, MO 65212, USA

*Corresponding Authors:
Guangfu Li, Ph.D
DVM Assistant Professor
Department of Surgery, Ellis Fischel Cancer Center
the University of Missouri
One Hospital Drive, Columbia, MO 65212, USA
Tel: 573-882-8454
Fax: 573-884-6054
E-mail: [email protected]
 
Kevin F. Staveley-O’Carroll M.D., Ph.D
Professor and Chair of Surgery
Director of Ellis Fischel Cancer Center
the University of Missouri, One Hospital Drive, Columbia
MO 65212, USA
Tel: 573-882-8454
Fax: 573-884-6054
E-mail: [email protected]

Received Date: June 20, 2016; Accepted Date: July 12, 2016; Published Date: July 18, 2016

Citation: Qi X, Kit LS, Liu D, Kim DY, Ma L, et al. (2016) Development of Laser Immunotherapy to Study Its Impact on Immune Response in Mice with Hepatocellular Cancer. J Clin Cell Immunol 7:438. doi: 10.4172/2155-9899.1000438

Copyright: © 2016 Qi X, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Manipulation of immune system toward the rejection of established cancers has become the standard of care in some patients. Here we propose the development of an in situ autologous cancer vaccine, inCVAX, for the treatment of hepatocellular cancer (HCC). inCVAX is based on the induction of local immunogenic cancer cell death combined with local dendritic cell stimulation by intratumoral injection of the immune-activator N-dihydro-galactochitosan (GC). In a first set of experiments, cellular and molecular studies were performed to investigate the effect of inCVAX on immune activation in a murine model of HCC that we previously developed. Once large tumors were formed in mice, the tumor is surgically exposed and a laser fiber was inserted into the center of an individual tumor mass. Using a 10 mm diffuser tip, laser irradiation of 1.5 W was applied to heat the tumor at different durations (6-10 min) to assess tolerability of photothermal application at different temperatures. The laser application was followed by immediate injection of GC, and each mouse received one laser treatment and one GC injection. ELISA was used to assess the level of cytokines; immunohistochemical staining was conducted to analyze the effect of inCVAX on immune cell tumor-filtration and expression of tumor-specific antigens (TSAs) and tumor-associated antigens (TAAs). Results indicate that survival correlated to thermal exposure. At lower temperatures the photothermal effect was sufficient to induce tumor necrosis, but without obvious complication to the mice, although at these temperatures the treatment didn’t alter the level of TSAs and TAAs, so further optimization is suggested. Nevertheless, in response to the inCVAX treatment, cytotoxic cytokine IFN-γ was significantly increased, but suppressive cytokine TGF-β was dramatically reduced. Furthermore, inCVAX prompted tumor infiltration of CD3+, CD4+, and CD8+ T cells; but modulated macrophage subsets differently. In conclusion, while the protocol needs further optimization, it would appear that inCVAX for the treatment of HCC activates an immune response in tumor-bearing mice, which in turn may have potential for the treatment of HCC.

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