Eradication of tumor growth via biolistic transformation with allogeneic MHC genes

Abstract

Particle acceleration-mediated biolistics transformation has been rapidly adopted as a versatile technology for gene delivery since its original application as a physical method for delivery of foreign genes into higher plants. We have designed a versatile hand-held gene gun device for the genetic immunization of animals in vivo. The gene gun is driven by air blast and therefore does not require helium gas or vacuum for its function. In this report, we have employed this gene gun device to introduce allogenic H-2Kb DNA directly into tumor nodules of K36 tumor-bearing AKR/J mice. Expression of the exogenous H-2Kb gene led to the regression of well-established K36 tumors. This tumor regression was correlated with the generation of potent secondary CTL responses against the K36 tumor cells following expression of the exogenous H-2Kb gene in the K36 tumor cells. Furthermore, it was observed that H-stimulator cells could stimulate the generation of both allogeneic and tumor-specific secondary CTL responses whereas mitomycin-C treated tumor cells could only stimulate tumor-specific secondary CTL responses. This approach of introducing allogeneic MHC genes directly into cutaneous tumor lesions via biolistics transformation of tumor cells in vivo can potentially be developed into an effective method for cancer gene therapy.