Developing novel cancer patient-derived xenografts (PDXs) that support evaluation of immunotherapies enhancing human T cell functionality in the absence of graft versus host disease   

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Presentation Time: 11:30 AM - 12:45 PM
Poster Board Number: B219
Abstract ID: 5962

Presenting Author:
Christa Cheatham , Comparative Medicine Resident at Univ. of Missouri, Columbia

Abstract:

Better preclinical models are needed to study immunotherapies targeting the adaptive immune system. We have developed several PDX models of human non-small cell lung cancer (NSCLC) by surgically implanting resected tumors subcutaneously in NOD scid gamma (NSG) mice. The NSCLC PDX models that we have established in our laboratory retain tumor-associated CD3+, CD4+, and CD8+ human T cells after multiple passages without causing graft versus host disease in the grafted mice. We have used such PDX human T cell positive models to test the potential therapeutic efficacy of a novel immunotherapy targeting human CD3 complex using a monovalent Fab fragment (mono-OKT3-Fab). We have compared the growth of PD-L1 positive NSCLC grafts in NSG mice treated with either anti-human PD-L1 antibodies, Mono-OKT3-Fabs or appropriate immunoglobulin controls. Whether implanting metastatic or non-metastatic, we observed that mice treated with either anti-PL-1 mAbs or Mono-OKT3-Fab had a significantly reduced tumor burden and increased survival over control mice. Additionally, when treating the metastatic NSCLC models with a combination of anti-human PD-L1+Mono-OKT3-Fab tumor grafts grew significantly slower, and mice prolonged their survival over control-treated mice. In summary, our PDX models are a useful tool for comparative studies of immunotherapies targeting human adaptive lymphocytes in the absence of the confounding effects of GVHD.