IL-1/IL-3 gene therapy of non-small cell lung cancer (NSCLC) in rats using 'cracked' adenoproducer cells.
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 alpha and for rat interleukin-3 beta 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.
Esandi
M C
MC
Department of Molecular Cell Biology, Leiden University, The Netherlands.
van Someren
G D
GD
Bout
A
A
Mulder
A H
AH
van Bekkum
D W
DW
Valerio
D
D
Noteboom
J L
JL
D000256:Adenoviridae; D000818:Animals; D002289:Carcinoma, Non-Small-Cell Lung / Q000628:therapy*; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D007375:Interleukin-1 / Q000235:genetics*; D007377:Interleukin-3 / Q000235:genetics*; D008175:Lung Neoplasms / Q000628:therapy*; D051381:Rats; D011919:Rats, Inbred Strains
D007375:Interleukin-1; D007377:Interleukin-3