¹Section Gene Therapy, Department of Molecular Cell Biology, Leiden University, Leiden, The Netherlands

²Department of Biologya y Bioquimica Universidad Nacional del Sud, Bahia Blanca, Argentina

³IntroGene BV, Leiden, The Netherlands

⁴Pathologisch Laboratorium, Dordrecht, The Netherlands

⁵Department of Clinical Oncology, Leiden University Hospital, The Netherlands

Cytokine gene therapy was studied in established L42 tumours in syngeneic rats. L42 is a transplantable non-immunogenic non-small cell lung cancer (NSCLC). Genes coding for human interleukin-1 and for rat interleukin-3 were transferred by injecting producer cells of recombinant adenovirus vectors into the tumour in attempts to achieve high concentrations of the cytokines inside the tumor without systemic toxicity. Limited tumour growth delay was obtained with viable producer cells. For logistic reasons stocks of pooled frozen producer cells allowed intensive treatment of groups of tumour bearing rats. The cells were lysed by thawing before administration. Ten daily injections of such 'cracked' producer cells induced reproducible tumour responses. These were due to local release of cytokines, not to systemic effects. Growth retardation also occurred in contralateral tumours which were not injected. When rats carrying established tumours were vaccinated with lysates of tumours collected during treatment with 'cracked' producer cells, significant tumour growth retardation was obtained. We speculate that both cytokines, if produced at sufficiently high concentrations in tumours, induce inflammation which in turn initiates an immune response against tumours growing at a distant site. These findings seem to justify further exploration of IL-1 and IL-3 gene transfer for the treatment of cancers.

gene therapy; interleukin-1; interleukin-3; lung cancer; adenovirus; therapeutic vaccination