Study Start Date: 08/01/2011
Study End Date: 07/31/2013

Evaluation of Listeria monocytogenes expressing recombinant huHer2/neu to stimulate anti-tumor immunity and prolong survival times in dogs with appendicular osteosarcoma
Canine osteosarcoma (OSA) is a common, highly aggressive cancer that frequently affects the long bones of large breed dogs. Current therapy consists of limb amputation plus systemic chemotherapy. However despite therapy 90% of patients die within one year of diagnosis from metastatic disease. The immune system plays an important role in identifying and specifically targeting cancerous cells in the body. In this proposal we will utilize a novel approach to stimulate anti-tumor immunity in dogs that have undergone limb amputation for the treatment of OSA. The approach utilizes the intracellular bacteria Listeria monocytogenes that has been genetically modified to express a tumor associated antigen, Her-2/neu to sitmulate an immune response against tumor cells remaining following removal of the primary tumor (limb amputation). Previous studies in mice have shown that this approach rapidly and effectively induces a potent immune response against cancerous cells expressing Her-2/neu and provides a significant survival advantage over controls. The goal of the work is to determine a safe and effective dose of recombinant Listeria monocytogenes that induces Her-2/neu specific T cell immune responses in dogs with appendicular OSA. In addition we will determine whether induced immunity can lead to protection from the development of metastatic disease in dogs with Her-2/neu expressing OSA.

Study Design:
Prospective

Sample Size:
9-18 dogs

Inclusion Criteria:

• Dogs with histopathological diagnosis of her2/neu positive OSA (sample of tumor can be sent to UPenn to confirm expression of her2/neu at the time of biopsy or amputation - please call Nicola Mason for further details).
• Dogs undergoing limb amputation and standard carboplatin therapy for treatment of OSA
• Dogs with no other systemic disease
• Life expectancy >3 months

Exclusion Criteria:

• Dogs that have not undergone limb amputation
• Dogs with concurrent systemic disease
• Dogs with evidence of thoracic metastases
• Dogs with impaired immune function (to be determined at the time of enrollment)

Study Controls:
NA

Study Endpoints:
Primary end-points:

1. Induction of her2/neu specific cytotoxic immune responses
2. Determination of safe and biologically effective dose

1. Disease free interval

Samples
Clinicians will be required to submit bone biopsies - fresh tissue placed in sterile saline and transported overnight to UPenn for evaluation of her2 expression prior to enrollment. Alternatively, patients will have biopsies performed at UPenn prior to enrollment.

Costs/Reimbursments
Participants will receive 3 doses of the Listeria vaccine, 3 weeks apart following standard carboplatin chemotherapy at no charge. Participants will also receive routine evaluations including blood work, thoracic radiographs and immune tests every 2 months after vaccination for a total of 18 months.

Full Disclosure information:

• The study is funded by a grant from Advaxis Incroporated.
• The investigator does not have a conflict of interest.
• The study will be published if results are negative.

Date published: 11/01/2011