Abstract
Background; We investigated, as a neoadjuvant to surgical therapy, the effect of a gene therapy of the primary tumour on the progression of minimal residual disease to overt liver metastases. The gene construct coding for the immunostimulatory molecules GM-CSF and B7-1 was delivered to the growing tumour by electroporation in Balb/C mice.
Methods; JBS fibrosarcomas were induced subcutaneously and were randomised at 80mm3 to control and treatment groups. One day prior to treatment, the portal circulation was seeded with tumour cells. Gene delivery was assessed by in vivo imaging, cytokine measurement and anti–tumour cytotoxicity (in vitro and in vivo). Responses were determined by liver examination.
Results; Gene expression and cytokine production was evident in treated tumours. Development of liver metastases was inhibited by neoadjuvant therapy in all 8 animals, in comparison to none of the control animals (n = 6) (average liver weight=0.99 g vs. 1.748 g. p< 0.03.) Metastases were confirmed histologically. Cytotoxicity studies and rechallenge confirmed development of specific T cell antitumour responses after gene therapy.
Conclusions; Immunogene therapy of the primary tumour induces effective anti–tumoural responses and inhibits the development of liver metastases. This strategy could be developed for neoadjuvant therapy of some human cancers.
Correspondence should be addressed to Ms Larissa Welti, Scientific Secretary, EFORT Central Office, Technoparkstrasse 1, CH-8005 Zürich, Switzerland
