Paper describes well-established protocols for PDAC orthotopic tumor homograft model development and immunoprofiling
(San Diego, Calif., November 15 2018) — Crown Bioscience, a global drug discovery and development services company providing translational platforms to advance oncology, inflammation, cardiovascular and metabolic disease research, has recently published in the Journal of Visual Experiments the establishment and immunological characterization of PDAC orthotopic tumor homograft models.
Pancreatic ductal adenocarcinoma (PDAC) research represents an area of high unmet medical need. PDAC fails to respond to a range of cancer therapies, including immunotherapy, partially due to an abundant tumor microenvironment (TME), that protects tumor cells from treatment. The development of new therapeutic and combination strategies requires highly relevant preclinical models recapitulating the complexity of PDAC tumors including the TME.
Transplantable PDAC models, developed by passaging primary tumors from GEMM or carcinogen-induced models into immunocompetent syngeneic hosts, provide an ideal model for pharmacology studies. However, standard subcutaneous modeling may not provide the specific tissue environment to fully recapitulate human disease.
The orthotopic PDAC homograft models developed in this publication capture the morphology of human tumors with enriched stromal content which is more suitable for preclinical pharmacology evaluation. The publication demonstrates that the TME of orthotopic transplantation differs from common subcutaneous transplantation, and indicates that this approach could better mimic human PDAC, and be more predictive of I/O treatment in patients which is also highly dependent on the TME.
In addition, the methods of marker panel design and gating strategies for comprehensive immune phenotyping using flow cytometry described in the publication can be applied to a variety of murine models and could be useful for immuno-oncology researchers working on various disease indications.
“These orthotopic PDAC homograft’s better reflect the microenvironment of the original tumor compared to standard subcutaneous models,” said Dr. Henry Li, Senior Vice President of Research and Innovation at CrownBio. “We expect that the detailed establishment of such models and characterization of their TILs (Tumor Infiltrate Leukocytes) will allow the identification of key immunological markers, either baseline, or the impact of the treatment, to help predict response or mechanism of the treatments.
More information on the publication can be found here: https://www.crownbio.com/publication/tme-profiling-ortho-pdac
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CrownBio is a global drug discovery and development solutions company providing translational platforms to advance oncology, inflammation, cardiovascular and metabolic disease research. With an extensive portfolio of relevant models and predictive tools, CrownBio enables clients to deliver superior clinical candidates.
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