An approach of combined loco-regional adoptive immunotherapy and subcutaneous vaccination by allogeneic-IL2 gene-transfected tumor cell lines admixed with autologous tumor cells in patients with relapsed glioblastoma

Introduction: Prognosis of glioblastoma patients is very poor. Some encouraging results using immunotherapeutic techniques have been recently reported (both using antibody in passive loco-regional radio-immunotherapy and local adoptive therapy using lymphokine-activated killer cells (Lak) and interleukin-2 (IL2). Vaccination using autologous glioblastoma tumour cells transfected with IL2-human gene have been also attempted. Encouraged from the reported results, although episodic, we decided to evaluate the feasibility of a combined local and systemic immunotherapeutic approach using both adoptive-passive and active immunising techniques in 7 relapsed patients, already conventionally treated with surgery and radio-chemotherapy. Methods: As loco-regional therapy, in 5-60 days, 7 patients were treated with 0.4-1 M IU in doses of 0.1 M IU of recombinant alfa-interferon, 6 with 2-24 × 103 units of IL2, 4 with 11-58 × 106 of autologous Lak cells, 2 with 11-2200 × 106 of cells preincubated with 100 picogramme of bispecific murine monoclonal (anti-CD3 and anti-tenascin antibodies), 4 with 5-10 ml of human complement-fixing in vitro produced antibodies reacting with the tumours. The systemic treatment was performed in 2 patients with subcutaneous injection of 13-15 millions of autologous formalin-fixed glioblastoma tumour cells and 20-30 × 106 of allogeneic IL2-gene transfected and irradiated tumour cells. Results: In one of the patients we noticed adverse side effects. 3 died in 20-120 days with progression of disease; in one of them the progression was observed only in the lesion that was not treated. In one patient we noticed regression of the tumour 2 months after treatment. Of the remaining 3 patients, still alive, one is in progression. Conclusions: Although the observation period is too short for any clinical consideration, because one of the studied patients showed a good immunisation towards the autologous and allogeneic tumour cells and because of the complete absence of any adverse clinical side effects, such a combined loco-regional and systemic treatment, in our opinion, seems to be promising.