The Potential of Suicide plus Immune Gene Therapy for Treating Osteosarcoma: the Experience on Canine Veterinary Patients

FINOCCHIARO LME, SPECTOR A, ROSSI UA, GIL CARDEZA ML, SUÁREZ JL, RIVEROS MD, VILLAVERDE MS Y GLIKIN GC

Sarcoma: Symptoms, Causes and Treatments

E.J. Butler

Año: 2012;

Comparative oncology amalgamates the experience on naturally occurring cancers in veterinarypatients into more general studies of cancer, especially those focused on the human disease. Naturally occurring tumors in dogs have clinical and biological similarities to human cancers that are difficult to replicate in other model systems. Osteosarcoma (OSA) accounts for approximately 85% of primary bone cancers in the dog. It is a common cancer of large to giant breed dogs, and it occurs primarily in the appendicular skeleton. Being a common and highly metastatic tumor, it does not have additional treatment options when adjuvant chemotherapy has failed against its disseminated form. Even with removal of the primary tumor, before spread of the cancer is clinically detectable, metastases to lung, bone, or other sites eventually develop in almost all dogs. Palliative radiation therapy for bone pain is indicated in those dogs that do not undergo amputation or a limb-sparing surgery. Standard treatments result in median survival rates ranging between 78 and 130 days. In such context the need to develop new treatments to fight OSA is compelling. While most of cancer gene therapy for canine veterinary patients was aimed to spontaneous melanoma and some to primary canine soft-tissue sarcomas, only one was specifically aimed to OSA. Therefore, we propose a new treatment combining: (i) the local antiproliferative effects of interferon-β and HSV-thymidine kinase suicide gene therapy with (ii) the systemic effects triggered by OSA antigens in an immunostimulatory environment created by the slow secretion of granulocyte and macrophage colony-stimulating factor and interleukin-2. Beyond the high safety standard of the proposed treatment on six canine osteosarcoma patients, four of them survived more than 6 months (among them, one largely exceeded 1 year). In addition, the treatment prevented or delayed local relapse, regional metastases and distant metastases, suggesting a strong systemic antitumor immunity.We are presenting detailed evidences of two cases of a very successful outcome: (i) a first onepresenting a long term recurrence-free period after tumor surgical excision and (ii) a second one of a long-lasting complete remission without surgical intervention.As a conclusion of this work we suggest that the use of this treatment, associated or not to the surgical removal of the tumor (depending on the initial stage of the disease), would be safe and could delay or prevent recurrence and metastases, with the consequent quality of life and survival rate improvement. To establish the treatment efficacy, the encouraging results presented here warrant the proposal of a subsequent trial including a representative amount of canine patients.