Tumor Vaccine Combined with Cytokines and Suicide Gene Therapy for Canine Spontaneous Soft Tissue Sarcomas

FINOCCHIARO, LILIANA M.E.; VILLAVERDE, MARCELA S.; GIL CARDEZA, MARÍA L.; RIVEROS, MARÍA D.; GLIKIN, GERARDO C.

San Diego, CA, USA.

Congreso; American Society of Gene Therapy (ASGT). 12th Annual Meeting.; 2009

American Society of Gene Therapy.

Soft-tissue sarcomas (STS) that arise from many non-bony connective tissues comprise approximately 15% of all skin and subcutaneous tumors in the dog. As an adjuvant treatment of surgery, we evaluated the safety, efficacy, and antitumor effects of a vaccine containing both canine STS lysates and genetically modified cells secreting human granulocyte-macrophage colony-stimulating factor (hGM-CSF) and human interleukin-2 (hIL-2), simultaneous to in situ cationic lipid mediated canine interferon-B (cIFN-B) and herpes simplex thymidine kinase (HSVtk) suicide gene therapy. Ten canine patients were subjected to: (i) surgery followed by multiple injections of DMRIE:DOPE-complexed plasmid DNA encoding cIFN-B and HSVtk co-administrated with ganciclovir (GCV) in the areas surrounding the excised tumor; (ii) periodic subcutaneous injection of living irradiated xenogenic cells secreting hGM-CSF and hIL-2 mixed with formolized allogeneic and autologous tumor lysates concurrent with (iii) periodic multiple intra and/or peritumoral injections of cIFN-B and HSVtk-carrying lipoplexes and GCV, in cases of partial tumor resection or local relapse. While some patients developed indurations at the vaccination sites, the treatment did not produce significant changes in complete blood counts or serum biochemical parameters. Systemic toxicity, organ dysfunction or fever was not found in any patient. In those patients presenting local relapse (5 of 10), the suicide gene plus cIFN-B treatment induced local antitumor activity evidenced by the objective responses (2 complete, 1 partial) and stable disease (1), while local disease progressed in only 1 of those 5 patients. In addition, the treatment controlled regional metastases (lymph nodes) that developed only in 2 of 10 patients, and completely abolished distant metastases (as evidenced by X-rays and ultrasound), suggesting a strong systemic antitumor immunity. The most encouraging result was the wide survival times of most patients (4 more than 2 years, 3 more than 1 year). In conclusion, the use of this treatment after surgical removal of the tumor is safe and could delay or prevent post-surgical recurrence and metastases, with the consequent quality of life and survival rate improvement. A subsequent trial including a representative amount of canine patients bearing different types of STS is being tested for the efficacy of the treatment.