Development of an allogeneic whole-cell tumor vaccine expressing xenogeneic gp100 and its implementation in a phase II clinical trial in canine patients with malignant melanoma |
| |
Authors: | AN Alexander MK Huelsmeyer Ann Mitzey RR Dubielzig ID Kurzman EG MacEwen DM Vail |
| |
Institution: | (1) Department of Medical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, 2015 Linden Drive, Madison, WI 53706, USA;(2) Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, 2015 Linden Drive, Madison, WI 53706, USA;(3) The MacEwen Center for Clinical Trials and Translational Research, School of Veterinary Medicine, University of Wisconsin-Madison, 2015 Linden Drive, Madison, WI 53706, USA;(4) University of Wisconsin Comprehensive Cancer Center, University of Wisconsin-Madison, 2015 Linden Drive, Madison, WI 53706, USA;(5) Animal Cancer Center, Colorado State University, 300 West Drake Rd, Fort Collins, CO 80523-1620, USA |
| |
Abstract: | A xenogeneic melanoma-antigen-enhanced allogeneic tumor cell vaccine (ATCV) is an appealing strategy for anti-cancer immunotherapy
due to its relative ease of production, and the theoretical possibility that presentation of a multiplex of antigens along
with a xenogeneic antigen would result in cross-reaction between the xenogeneic homologs and self-molecules, breaking tolerance
and ultimately resulting in a clinically relevant immune response. In this study, we evaluated the efficacy of such a strategy
using a xenogeneic melanoma differentiation antigen, human glycoprotein 100 (hgp100) in the context of a phase II clinical
trial utilizing spontaneously arising melanoma in pet dogs. Our results demonstrate that the approach was well tolerated and
resulted in an overall response rate (complete and partial response) of 17% and a tumor control rate (complete and partial
response and stable disease of >6 weeks duration) of 35%. Dogs that had evidence of tumor control had significantly longer
survival times than dogs that did not experience control. Delayed type hypersensitivity (DTH) to 17CM98 canine melanoma cells
used in the whole cell vaccine was enhanced by ATCV and correlated with clinical response. In vitro cytotoxicity was enhanced
by ATCV, but did not correlate with clinical response. Additionally, anti-hgp100 antibodies were elicited in response to ATCV
in the majority of patients tested; however, this also did not correlate with clinical response. This approach, along with
further elucidation of the mechanisms of tumor protection after xenogeneic immunization, may allow the development of more
rational vaccines. This trial also further demonstrates the utility of spontaneous tumors in companion animals as a valid
translational model for the evaluation of novel vaccine therapies.
E.G. MacEwen deceased |
| |
Keywords: | Tumor cell vaccine Allogeneic Immunotherapy Melanoma Dog Glycoprotein-100 |
本文献已被 PubMed SpringerLink 等数据库收录! |
|