Title: 1829 - Novel Syngeneic HNSCC Animal Models to Identify New Immune-oncology Strategies
Zhiyong Wang (Presenter)
Victoria Wu, UC San Diego
Michael Allevato, UC San Diego
Lynn Vitale-Cross, NIH
Mara Gilardi, UC San Diego
Daniel Martin, NIH
Juan Valera, Sanford Research
James Mcdermott, UC San Diego
Qianming Chen, Sichuan University
J.Silvio Gutkind, UC San Diego
Objectives: Recent revolutionary therapeutic strategies restoring T cell mediated anti-tumor immunity in head and neck squamous cell carcinoma (HNSCC) by targeting immune checkpoints, such as PD-1 and PD-L1, have demonstrated durable remissions. However, the overall response rate to these immunotherapies in HNSCC is only ~20%. There is a need to stratify patients that may respond best to these immune oncology (IO) agents, and to identify more effective therapeutic options. For this, pre-clinical animal models with a fully functioning immune system recapitulating the complexity of the tumor microenvironment are strictly required. Only few syngeneic mouse models are available, which are driven by ras oncogenes that are very infrequent in HNSCC. Therefore, animal models which are directly relevant to human HNSCC are urgently needed.
Methods: 4NQO, a carcinogen that mimics tobacco consumption was used to induce oral cancer in C57/Bl6 mice. HNSCC cell lines were isolated from these primary lesions (designated 4MOSCC1-4), sequenced, and used for the development of HNSCC tumors when orthotopically transplanted into the tongue of immunocompetent C57Bl/6 mice; Extensive characterization of their cancer-immune environment was performed by flow cytometry, Nano-string, and RNAseq approaches.
Results: 4MOSCC exhibit typical HNSCC histology and tobacco-related mutations, and are highly infiltrated by immune cells, similar to ~70% of human HNSCCs. 4MOSCC3 tumors respond to anti-PD-1 treatment, while 4MOSCC1 tumors, which do not express PD-L1 (<1% of cells), failed to respond to anti-PD-1 treatment. 4MOSCC3 is immunogenic, as vaccination with irradiated cells promote the rejection of subsequent re-challenge. Their use to explore novel precision immune co-therapies (PICT) will be presented.
Conclusions: Novel syngeneic HNSCC animal models grown orthotopically in wild type mice were established and characterized. These models, which reflect typical clinical situations, may provide unique opportunities to investigate the interplay between HNSCC and the immune system and to identify new IO strategies.
This abstract is based on research that was funded entirely or partially by an outside source:
National Natural Science Foundation of China (81602376,81520108009, 81621062), 111 Project of MOE (B14038), China；National Institute of Dental and Craniofacial Research (NIH/NIDCR) 1R01DE026644-01,USA
The submitter must disclose the names of the organizations with which any author have a relationship, the nature of the relationship, and the clinical or research area involved. The following is submitted: None