How to assess tumor-specific immune responses? Need to identify tumor-specific antigens, no mean feat since most of what a tumor expresses is similar to what normal cells express, at least as in so far as immunologically relevant material, Antigen – Wikipedia, is concerned. Genetically engineering the mouse thymoma cell line EL4 to express the Ovalbumin – Wikipedia (OVA) protein, i.e., EL4-OVA, created a research tool to do just that.

Since the 1990s, T cell transgenic mice (Transgene – Wikipedia) have become basic immunology research models du jour. Among the most popular models in particular are T cell transgenics on the RAG (Recombination-activating gene – Wikipedia) knock out (KO) background. Knocking out the RAG-1 and -2 genes puts an end to the capacity for generating T and B cells. Thus a T cell transgenic mouse on the RAG KO background contains a monoclonal population of T cells expressing a single TCR (T-cell receptor – Wikipedia).

One of the most popular antigenic specificities chosen for creating such T cell transgenic mice has been OVA. For example the T cell transgenic mice OT-1 and OT-II on the C57BL/6 – Wikipedia background have a monoclonal population of CD8 and CD4 T cells, respectively, specific for OVA peptides. OTOH, the DO11.10 is an OVA peptide-specific CD4 T cell transgenic mouse on the BALB/c – Wikipedia background. C57Bl/6 and BALB/c are standard inbred mouse strains.

The EL4 mouse thymoma cell line was derived from a C57Bl/6 mouse. Making it express OVA made it a useful tool to assess anti-cancer immune responses in an antigen-specific manner. Typically, OT I and/or OT II T cells are injected into EL4-OVA tumor-bearing C57Bl/6 or C57Bl/6 RAG KO or WT (wild type) mice in various permutations and combinations. This makes it possible to use anti-OVA T cell responses as a surrogate for assessing anti-tumor T cell responses.