Oncolytic adenoviral therapy is a promising approach for pancreatic cancer. However, the lack of a suitable immune-competent mouse model to study oncolytic adenovirus (OA) antitumor activity precludes the full evaluation of the virotherapy. Human OA are generally very limited to produce infectious viral progeny in murine cancer cells what hinders the study of the immunological activity linked to OA replication.

In the current work we established the murine KPC cell line from pancreatic tumors developed in LSL-KRasᴳ¹²ᴰ; LSL-Tp53R¹⁷²ᴴ; Pdx-Cre mice. KPC cells were susceptible to adenoviral infection. Transduction efficiency in KPC cells was similar to the murine lung cancer CMT64.6 cells and consistently higher than in the PAN02 or CT26 murine cells. KPC infected cells with a replicative-competent adenovirus displayed cytopathic effect and generated a progeny of infective virions. In contrast, the viral load produced by CMT64.6 cells was rather limited. Viral genome replication revealed a number of intracellular viral genomes similar between both cells lines that resulted in similar expression of viral proteins at the mRNA level. Of notice, viral protein expression was remarkably superior in KPC cells when compared to CMT64.6 cells suggesting that adenoviral protein translation in KPC cells was less impeded. Interestingly, the OA AdNuPARmE1A displayed strong cytotoxicity in KPC cells and triggered antitumor activity in KPC xenografts developed in immunodeficient mice.

In summary, our data shows that KPC cells are semi-permissive to human OA replication rendering KPC syngeneic xenografts an interesting model to evaluate the multifaceted antitumor activities of OA for pancreatic cancer.