Abstract LB-113: Recombinant HER2/Neu expressing Listeria combined with radiation safely delays tumor progression and prolongs overall survival in a phase I clinical study in canine osteosarcoma

The purpose of this study is to determine the safety and efficacy of a highly attenuated recombinant Listeria monocytogenes expressing a chimeric human HER2/neu (Lm-LLO-HER2/neu) in combination with palliative radiation (RT) to induce HER2 specific immunity and delay tumor progression in dogs with spontaneous osteosarcoma (OSA). Dogs develop OSA that recapitulates many aspects of human OSA, and are recognized as a clinically relevant, large animal model in which to evaluate novel therapies. Previously we have shown that Lm-LLO-HER2/neu administration to dogs with HER2+ OSA following amputation and chemotherapy is safe, breaks tolerance to HER2 and prolongs overall survival.Ten systemically healthy dogs with histopathologically confirmed, treatment naïve, HER2+ appendicular OSA, and no evidence of cardiac or metastatic disease were enrolled. All dogs received 2 × 8Gy fractions of RT on consecutive days, followed by the first of 8 intravenous doses of Lm-LLO-HER2/neu given once every 3 weeks. Dogs were monitored at each treatment and every 2 months after for systemic and cardiac toxicity, lameness and quality of life (QOL) (using a validated owner questionnaire). Radiographs were performed at baseline, week 10, week 22 and every 2 months thereafter to determine the effect on the primary tumor and development of pulmonary metastases. PBMCs were collected every 3 weeks to evaluate HER2/neu specific T cell responses. The primary endpoint was time to progression; secondary end po...
Source: Cancer Research - Category: Cancer & Oncology Authors: Tags: Clinical Research (Excluding Clinical Trials) Source Type: research