Tumor Homograft Models for Efficacy and PD Assessment

New immuno-oncology models are needed specifically for pharmacology and efficacy studies. Widely used syngeneic models are limited in number and cancer type, and larger collections of GEMM (featuring clear molecular disease drivers) are not suitable due to unsynchronized tumor progression and long latency periods.

At CrownBio we have developed MuPrime, tumor homograft models combining the benefits of GEMM with an improved operational simplicity, consistency, and growth, similar to syngeneic models.

MuPrime models provide an ideal platform to investigate your novel surrogate or cross-reactive immunotherapies with competent murine immunity, and the ability to synchronize tumor growth for pharmacology studies.

MuPrime models are subcutaneous or orthotopic homografts from spontaneous, carcinogen-induced, or CRISPR/Cas9-engeneered GEMM tumors into immunocompetent syngeneic hosts.

The resulting tumor homografts are never manipulated or adapted to grow in vitro, similar to parental GEMM. This means MuPrime models mirror original mouse tumor histopathology and genetic profiles, with various differentiation phenotypes, rich microenvironments, and cancer stem cell driven disease.

Key Advantages of Tumor Homografts

MuPrime tumor homografts are a unique platform to progress your immuno-oncology drug discovery, providing many advantages over traditional syngeneics or GEMM:

• Presence of a relevant tumor stroma
• Mirror original murine tumor histopathology
• Cancer stem cell driven disease
• Encompass disease-specific mutations of human cancers
• Lower mutational load than syngeneics
• Availability of a diverse range of cancer types and oncogenic drivers deriving from various GEMMs

Fully Validated Models

Models are fully validated through RNAseq and immunohistochemistry to confirm gene expression and mutational status. Response to standard of care agents as well as immunotherapy are also evaluated for our validated MuPrime models. A detailed baseline immune profile is also provided, making tumor homografts the ideal system to interrogate your novel agent as well as combination strategy.

Original GEMM tumor	MuPrime tumor (passage 0)	MuPrime tumor (passage 2)

Figure 1 Sample Pathology QC: mBR6004 MuPrime breast cancer tumors conserve original GEMM tumor histopathology through passages

Figure 2 Sample Model Response to Immunotherapy: Response to anti-PD-1 and anti-CTLA-4 evaluated in the mBR6004 breast cancer MuPrime model