Cell Therapy for Metastatic Osteosarcoma

In this study we will investigate the therapeutic potential of a type of white blood cell known as invariant natural killer T (iNKT) cells that are made from the blood of a healthy donor dog. iNKT cells are potent immune cells that kill cancer cells in mouse models and in some human cancer patients. In this study, we will use iNKT cells that express a cancer targeting receptor known as a chimeric antigen receptor (CAR). The CAR directs the modified iNKT cells to the cancer cells which are then killed. The CAR-iNKT cells also will further activate the patient’s own immune system to help kill the cancer cells. The purpose of this study is to determine the safety of CAR-iNKT cells, their maximum tolerated dose, how long they will remain in the patient and their effectiveness against bone cancer that has spread to the lungs. 

Contact:

Mary Beth Boland: mboland@vet.upenn.edu

Location: University of Pennsylvania

Study Type: Interventional

Intervention: CAR iNKT cells

Inclusion Criteria

Dogs with a histopathological diagnosis of B7-H3+ appendicular osteosarcoma (the expression of the target protein B7H3, will be determined by the study team, who will perform immunohistochemistry on a portion of the archived tumor taken from the initial site in the leg either pre-amputation or at the time of amputation)

• Dogs who have undergone standard of care amputation followed by 4 to 6 doses of carboplatin 
• Dogs who have not received cytotoxic chemotherapy for at least 8 weeks
• Dogs with evidence of pulmonary metastatic disease
• Adequate hematologic parameters, and hepatic and renal function
• No significant co-morbidities
• Expected survival time of at least 2 months at the time of enrollment
• Body weight of at least 18kg

Exclusion Criteria

• Dogs without evidence of B7-H3 expression on primary appendicular osteosarcoma as determined by IHC
• Dogs receiving cytotoxic chemotherapy or who have received cytotoxic chemotherapy within the last 8weeks
• Clinically significant abnormalities on baseline complete blood count and/or biochemical profile
• Significant concurrent illness (including autoimmune or immune mediated disease or history of autoimmune or immune mediated disease, significant proteinuria, infectious disease etc.)
• Any unregulated chronic disease for which the dog is receiving daily medication. This includes but is not limited to: hyperadrenocorticism, neurologic disease, heart disease, liver disease, and/or renal disease

Potential Medical Benefits to Enrolled Animals 

The overall goal is to see either stable disease or regression of established pulmonary metastatic osteosarcoma lesions.

Potential Medical Risks to Enrolled Animals 

• Cytokine release syndrome – high fever, lethargy, inappetence, low blood pressure, fast heart rate, nausea, vomiting
• Graft versus Host Disease (GVHD) – CAR-iNKT cells could attack patient’s own tissues causing skin ulcerations, gastrointestinal symptoms, vomiting, and/or diarrhea.
• On target, off tumor cytotoxicity – damage to tissues in the body other than the cancer cells
• Dyspnea and tachypnea – difficulty breathing, rapid breathing
• Bone marrow suppression – increased susceptibility to infection
• Lethargy, fever, anorexia
• Nausea and vomiting
• Allergic reactions during cell infusion (facial and tongue edema, pruritis, vomiting, diarrhea). 

Financial Incentives for Study Participants 

Costs associated with treatment are covered.