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Journal article
Immunotherapy with a HER2-Targeting Listeria Induces HER2-Specific Immunity and Demonstrates Potential Therapeutic Effects in a Phase I Trial in Canine Osteosarcoma
Clinical cancer research, v 22(17), pp 4380-4390
01 Sep 2016
PMID: 26994144
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Purpose: Recombinant Listeria vaccines induce tumor-specific T-cell responses that eliminate established tumors and prevent metastatic disease in murine cancer models. We used dogs with HER2/neu(+) appendicular osteosarcoma, a well-recognized spontaneous model for pediatric osteosarcoma, to determine whether a highly attenuated, recombinant Listeria monocytogenes expressing a chimeric human HER2/neu fusion protein (ADXS31-164) could safely induce HER2/neu-specific immunity and prevent metastatic disease.
Experimental Design: Eighteen dogs that underwent limb amputation or salvage surgery and adjuvant chemotherapy were enrolled in a phase I dose escalation clinical trial and received either 2 x 10(8), 5 x 10(8), 1 x 10(9), or 3.3 x 10(9) CFU of ADXS31-164 intravenously every 3 weeks for 3 administrations.
Results: Only low-grade, transient toxicities were observed. ADXS31-164 broke peripheral tolerance and induced antigen-specific IFN gamma responses against the intracellular domain of HER2/neu in 15 of 18 dogs within 6 months of treatment. Furthermore, ADXS31-164 reduced the incidence of metastatic disease and significantly increased duration of survival time and 1-, 2-, and 3-year survival rates when compared with a historical control group with HER2/neu(+) appendicular osteosarcoma treated with amputation and chemotherapy alone.
Conclusions: These findings demonstrate that ADXS31-164 administered in the setting of minimal residual disease can induce HER2/neu-specific immunity and may reduce the incidence of metastatic disease and prolong overall survival in a clinically relevant, spontaneous, large animal model of cancer. These findings, therefore, have important translational relevance for children with osteosarcoma and adults with other HER2/neu(+) cancers. (C) 2016 AACR.
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Details
- Title
- Immunotherapy with a HER2-Targeting Listeria Induces HER2-Specific Immunity and Demonstrates Potential Therapeutic Effects in a Phase I Trial in Canine Osteosarcoma
- Creators
- Nicola J. Mason - University of PennsylvaniaJosephine S. Gnanandarajah - University of PennsylvaniaJulie B. Engiles - University of PennsylvaniaFalon Gray - University of PennsylvaniaDanielle Laughlin - University of PennsylvaniaAnita Gaurnier-Hausser - Drexel UniversityAnu Wallecha - AdvaxisMargie Huebner - ClinData Services Inc., Fort Collins, Colorado.Yvonne Paterson - University of Pennsylvania
- Publication Details
- Clinical cancer research, v 22(17), pp 4380-4390
- Publisher
- Amer Assoc Cancer Research
- Number of pages
- 11
- Grant note
- Advaxis Inc. Companion Animal Research Fund of the University of Pennsylvania Mari Lowe Center for Comparative Oncology, University of Pennsylvania
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Intensive Medical Sciences (IMS)
- Web of Science ID
- WOS:000383038200013
- Scopus ID
- 2-s2.0-84988663778
- Other Identifier
- 991019302291804721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Oncology