Combination of cytokine-enhanced vaccine and chemo-gene therapy as surgery adjuvant treatments for spontaneous canine melanoma
Autor: | Chiara Fondello, Liliana Maria Elena Finocchiaro, Gerardo Claudio Glikin, Lucrecia Agnetti |
---|---|
Rok vydání: | 2019 |
Předmět: |
Male
0301 basic medicine Ganciclovir medicine.medical_specialty Genetic enhancement medicine.medical_treatment Oral Surgical Procedures Antineoplastic Agents Biology Thymidine Kinase Bleomycin 03 medical and health sciences Dogs Postoperative Complications 0302 clinical medicine Genetics medicine Canine Melanoma Animals Dog Diseases Melanoma Molecular Biology Cells Cultured Vaccines Synthetic Chemotherapy Granulocyte-Macrophage Colony-Stimulating Factor Genetic Therapy Interferon-beta Suicide gene medicine.disease Surgery 030104 developmental biology Chemotherapy Adjuvant 030220 oncology & carcinogenesis Interleukin-2 Molecular Medicine Female Mouth Neoplasms Cancer vaccine Adjuvant medicine.drug |
Zdroj: | Gene Therapy. 26:418-431 |
ISSN: | 1476-5462 0969-7128 |
Popis: | After 6 years of follow-up treating 364 canine melanoma patients, we present here results about the proof-of-concept, safety, and efficacy of a new surgery adjuvant combined gene therapy. The adjuvant treatment (AT) group was divided in three arms as follows: (i) complete surgery plus vaccine (CS-V), (ii) complete surgery plus combined treatment (CS-CT), and (iii) partial surgery plus combined treatment (PS-CT). Besides the genetic vaccines composed by tumor extracts and lipoplexes carrying human interleukin-2 and granulocyte-macrophage colony-stimulating factor genes, the patients were subjected to combined treatment received in the post-surgical bed injections of lipid-complexed thymidine kinase suicide gene plus ganciclovir and canine interferon-β gene plus bleomycin. As compared with surgery-only treated controls (So), CS-CT and CS-V treatments significantly increased the fraction of local disease-free (from 20 to 89 and 74%) and distant metastases-free patients (M0: from 45 to 87 and 84%). Although less effective than CS arms, PS-CT arm demonstrated a significantly improved control of metastatic disease (M0: 80%) compared with So (M0: 44%). In addition, AT produced a significant 9.3- (CS-CT), 6.5- (CS-V), and 5.4-fold (PS-CT) increase of overall survival as compared with their respective So controls. In general terms, the AT changed a lethal disease into a chronic disease where 70% of CS-CT, 51% of CS-V, and 14% of PS-CT patients died of melanoma unrelated causes. These surgery adjuvant treatments delayed or prevented post-surgical recurrence and distant metastasis, and improved disease-free and overall survival while maintaining quality of life. These successful outcomes encourage assaying a similar scheme for human melanoma. |
Databáze: | OpenAIRE |
Externí odkaz: |