A mouse model for the study of anti-tumor T cell responses in Kras-driven lung adenocarcinoma

Cell Rep Methods. 2021 Sep 27;1(5):100080. doi: 10.1016/j.crmeth.2021.100080. Epub 2021 Sep 16.

Abstract

Kras-driven lung adenocarcinoma (LUAD) is the most common lung cancer. A significant fraction of patients with Kras-driven LUAD respond to immunotherapy, but mechanistic studies of immune responses against LUAD have been limited because of a lack of immunotherapy-responsive models. We report the development of the immunogenic KP × NINJA (inversion inducible joined neoantigen) (KP-NINJA) LUAD model. This model allows temporal uncoupling of antigen and tumor induction, which allows one to wait until after infection-induced inflammation has subsided to induce neoantigen expression by tumors. Neoantigen expression is restricted to EPCAM+ cells in the lung and expression of neoantigen was more consistent between tumors than when neoantigens were encoded on lentiviruses. Moreover, tumors were infiltrated by tumor-specific CD8 T cells. Finally, LUAD cell lines derived from KP-NINJA mice were immunogenic and responded to immune checkpoint therapy (anti-PD1 and anti-CTLA4), providing means for future studies into the immunobiology of therapeutic responses in LUAD.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adenocarcinoma of Lung* / genetics
  • Animals
  • Antibodies / metabolism
  • CD8-Positive T-Lymphocytes
  • Lung Neoplasms* / genetics
  • Mice

Substances

  • Antibodies