IL-1/IL-3 gene therapy of non-small cell lung cancer (NSCLC) in rats using ‘cracked’ adenoproducer cells

Abstract

Cytokine gene therapy was studied in established L42 tumour responses. These were due to local release of cytotumours in syngeneic rats. L42 is a transplantable nonkines, not to systemic effects. Growth retardation also immunogenic non-small cell lung cancer (NSCLC). Genes occurred in contralateral tumours which were not injected. coding for human interleukin-1␣ and for rat interleukin-3␤When rats carrying established tumours were vaccinated were transferred by injecting producer cells of recombinant with lysates of tumours collected during treatment with adenovirus vectors into the tumour in attempts to achieve 'cracked' producer cells, significant tumour growth retarhigh concentrations of the cytokines inside the tumor withdation was obtained. We speculate that both cytokines, if out systemic toxicity. Limited tumour growth delay was produced at sufficiently high concentrations in tumours, obtained with viable producer cells. For logistic reasons induce inflammation which in turn initiates an immune stocks of pooled frozen producer cells allowed intensive response against tumours growing at a distant site. These treatment of groups of tumour bearing rats. The cells were findings seem to justify further exploration of IL-1 and IL-3 lysed by thawing before administration. Ten daily injections gene transfer for the treatment of cancers. of such 'cracked' producer cells induced reproducible

A comparison of efficacy and toxicity between electroporation and adenoviral gene transfer

“…The L44 carcinoma was serially passaged on syngeneic rats. For the experiments, the tumours were established in the flank of rats by implanting small pieces (3 × 3 × 3 mm) of tumour tissue sub-cutaneously as described before [30]. …”

The involvement of IL-1 in tumorigenesis, tumor invasiveness, metastasis and tumor-host interactions

“…The efficiency of tumor cell vaccines, transiently expressing IL-1α, was also demonstrated by their ability to intervene in the growth of violent lymphoma cells. Treatment of a rat non-small cell lung cancer (NSCLC) with an adenovirus expressing genes of IL-1α and IL-3, induced growth retardation [156]. As adenovirus is immunogenic and is eradicated in mice after one to two weeks, these anti-tumor effects also result from transient expression of the cytokine.…”

Adenoviral gene transfer of angiostatic ATF-BPTI inhibits tumour growth

“…The subcutaneously growing tumour has a low microvascular density of 1.4% ± 0.6 (n = 10) and a volume doubling time of 10 days ± 0.8 (n = 10). For the experiments, the tumours were established in the flank of rats by implanting small pieces (3 × 3 × 3 mm) of tumour tissue sub-cutaneously as described before [41]. …”