Proven Intelligence Accelerating Next-Generation Therapies.

Executive Summary

Patient-Derived Xenograft (PDX) models provide a clinically relevant in vivo platform for evaluating the efficacy of next-generation therapies in oncology. By implanting patient tumor fragments into immunodeficient hosts, these models preserve the genomic and histological characteristics of the original human tumor. This approach offers a predictive advantage over traditional cell-line-derived xenografts for screening RNA payloads, gene editing systems, and cell-based modalities, directly informing candidate selection and minimizing clinical risk. Franklin Biolabs develops and validates custom PDX models within our >100,000 sq ft GxP-compliant facility, contributing to an 18-24 month timeline to IND.

Developing Clinically Relevant In Vivo Oncology Models

Standard oncology models often fail to recapitulate the complex tumor microenvironment and heterogeneity of human cancers. This disconnect can lead to poor clinical translation for novel therapeutic agents. Patient-Derived Xenograft models address this gap by maintaining the biological architecture and genomic integrity of the primary tumor, providing a more predictive system for efficacy testing.

Our scientific approach is informed by extensive experience in creating specialized xenograft platforms. The successful development of a humanized in vivo system for familial hypercholesterolaemia (PMID: 26081744) established a clear principle: patient-derived tissues can be used to build models that accurately reflect human disease states and predict the response to targeted advanced therapeutics. We apply this same principle to oncology, creating PDX models that serve as precise avatars for screening complex therapeutic candidates.

Applications for Next-Generation Therapies

The value of a well-characterized PDX platform is its ability to generate decision-making data for modalities that have complex mechanisms of action. High-fidelity in vivo intelligence for complex modalities is a prerequisite for successful clinical programs.

• RNA Therapeutics: Evaluate the in vivo delivery and anti-tumor activity of LNP-formulated mRNA, siRNA, or saRNA payloads in a human tumor context.

• Gene Editing Systems: Assess the efficacy and specificity of CRISPR-Cas9, base editor, or prime editor constructs delivered directly to the tumor.

• Cell-Based Modalities: Test the tumor-homing and cytotoxic potential of CAR-T, CAR-NK, or TCR-T therapies against solid tumors expressing relevant antigens.

The development of fit-for-purpose models is a foundational component of de-risking novel therapeutic programs, a concept validated in work developing nonhuman primate models for neovascular diseases (PMID: 15793254). That research demonstrated the necessity of creating specific in vivo systems to properly test novel agents. PDX models represent the application of this philosophy to personalized oncology.

GxP-Compliant Execution and Animal Welfare

All studies are designed and executed by our scientific team to meet program-specific objectives, from early proof-of-concept screening to formal IND-enabling toxicology studies. Our animal care and use programs are USDA-registered, and all work is conducted with a firm commitment to the 3Rs principles of Replacement, Reduction, and Refinement. This ethical framework is integrated directly into our study designs, ensuring both data integrity and the highest standards of animal welfare.