title: Suicide plus immune gene therapy prevents post-surgical local relapse and increases overall survival in an aggressive mouse melanoma setting.
abstract: In an aggressive B16-F10 murine melanoma model, we evaluated the effectiveness and antitumor mechanisms triggered by a surgery adjuvant treatment that combined a local suicide gene therapy (SG) with a subcutaneous genetic vaccine (Vx) composed of B16-F10 cell extracts and lipoplexes carrying the genes of human interleukin-2 and murine granulocyte and macrophage colony stimulating factor. Pre-surgical SG treatment, neither alone nor combined with Vx was able to slow down the fast evolution of this tumor. After surgery, both SG and SG + Vx treatments, significantly prevented (in 50% of mice) or delayed (in the remaining 50%) post-surgical recurrence, as well as significantly prolonged recurrence-free (SG and SG + Vx) and overall median survival (SG + Vx). The treatment induced the generation of a pseudocapsule wrapping and separating the tumor from surrounding host tissue. Both, SG and the subcutaneous Vx, induced this envelope that was absent in the control group. On the other hand, PET scan imaging of the SG + Vx group suggested the development of an effective systemic immunostimulation that enhanced (18)FDG accrual in the thymus, spleen and vertebral column. When combined with surgery, direct intralesional injection of suicide gene plus distal subcutaneous genetic vaccine displayed efficacy and systemic antitumor immune response without host toxicity. This suggests the potential value of the assayed approach for clinical purposes.
authors: Unidad de Transferencia Genética, Instituto de Oncología "Ángel H. Roffo", Universidad de Buenos Aires, Argentina.
authors: Marcela S
authors: MS
authors: Villaverde
authors: Cellvax Laboratoires, École Nationale Vétérinaire d'Alfort, France.
authors: Kristell
authors: K
authors: Combe
authors: Facultad de Ciencias Veterinarias, Universidad de Buenos Aires, Argentina.
authors: Adriana G
authors: AG
authors: Duchene
authors: Cellvax Laboratoires, École Nationale Vétérinaire d'Alfort, France.
authors: Ming X
authors: MX
authors: Wei
authors: Unidad de Transferencia Genética, Instituto de Oncología "Ángel H. Roffo", Universidad de Buenos Aires, Argentina.
authors: Gerardo C
authors: GC
authors: Glikin
authors: Unidad de Transferencia Genética, Instituto de Oncología "Ángel H. Roffo", Universidad de Buenos Aires, Argentina. Electronic address: gglikin@bg.fcen.uba.ar.
authors: Liliana M E
authors: LM
authors: Finocchiaro
mesh_terms: D000818:Animals; D019496:Cancer Vaccines; D002457:Cell Extracts; D062109:Dermatologic Surgical Procedures; D041722:Genes, Transgenic, Suicide / Q000235:genetics; D015316:Genetic Therapy / Q000379:methods*; D016179:Granulocyte Colony-Stimulating Factor / Q000235:genetics; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D007376:Interleukin-2 / Q000235:genetics; D016173:Macrophage Colony-Stimulating Factor / Q000235:genetics; D008546:Melanoma, Experimental / Q000235:genetics / Q000276:immunology / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D009364:Neoplasm Recurrence, Local; D009368:Neoplasm Transplantation; D012867:Skin / Q000473:pathology*; D012878:Skin Neoplasms / Q000235:genetics / Q000276:immunology / Q000628:therapy*
chemical_list: D019496:Cancer Vaccines; D002457:Cell Extracts; D007376:Interleukin-2; D016179:Granulocyte Colony-Stimulating Factor; D016173:Macrophage Colony-Stimulating Factor
keywords: DMRIE; GM-CSF; HSV-TK; IL-2; Melanoma vaccine; PET scan