AACR20 Poster 5616: Evaluate Immunotherapy Mechanism of Action with Immune Cell Lineage Specific DTR Models

Characterization of a Spectrum of DTR Models for Conditional Depletion of Specific Immune Cell Lineages

Ying Jin, Jiahua Zhou, Fengge Li, Ruilin Sun*, Annie X. An, Henry Q.X. Li, Davy X. Ouyang
*Shanghai Model Organisms Center, Inc., 3577 Jinke Rd, Shanghai, 201203 China

Cancer immunotherapies often work through more than one mechanism of action, mediated by multiple immune cell subsets. For example, we’ve previously shown that anti-PD-1 antitumor effects are predominately driven by CD8+ cytotoxic T cells, but are also led by CD4+ effector T cells in some tumors.

It’s critical to dissect the mechanism of action of specific immunotherapies by clarifying their role through different immune cell lineages. This data can guide rational approaches for monotherapy treatment as well as combination strategies.

This poster details the characterization of a series of immune cell specific diphtheria toxin receptor (DTR) models - transgenic mouse models in which specific immune cell subsets are easily depleted from the whole model following diphtheria toxin administration. These models provide important tools for examining the mechanism of action of various cancer immunotherapies.

Watch this Poster to Discover:

• How transgenic DTR mice are an alternative option to antibody-mediated approaches for depleting targeted immune cell populations, particularly valuable for lineages lacking appropriate cell surface markers to be targeted by mAbs, e.g. Tregs
  
  
• Characterization of Foxp3-DTR mice, in which MC38 tumor growth was remarkably inhibited after Treg removal, alongside elevated CD8+ and CD4+ T cells and decreased myeloid cells (CD11b+)
  
  
• Characterization of several other transgenic DTR mouse models with specificity to deplete various immune cell lineages (e.g. CD19, CD4), providing useful tools to study the effects of immune cells

Watch the Poster Now!