In order to create a physiologically relevant and reliable model for pre-clinical testing of immunotherapies, we have developed an in vivo hybrid murine model in which lung adenocarcinomas are driven by Kras mutation and Tp53 deletion in the KP GEMMs, and the TMB is increased to levels similar to human cancer by the concomitant administration of MNU in vivo. The gene discussed is TP53; the disease is lung adenocarcinoma.