For lentiviral-based cell therapies, a successful preclinical safety submission to the EMA hinges on a histology strategy that directly addresses vector-specific biological activity. Standard toxicology assessments are insufficient. An effective program must integrate specialized molecular pathology techniques with classical histology to investigate potential insertional mutagenesis, long-term transgene expression, and sustained host immune responses in relevant tissues.

The permanent integration of lentiviral vectors into the host genome presents unique safety questions that must be answered with tissue-based evidence. A robust histology plan provides the contextual data to interpret findings from biodistribution, toxicology, and efficacy studies.

Our approach focuses on several key analytical pillars:

• Vector Integration and Proliferation: Histological evaluation of all relevant tissues for any morphological evidence of abnormal cellular growth or dysplasia. These findings are correlated with vector copy number (VCN) data to build a complete safety profile.

• Non-target Tissue Biodistribution: Microscopic examination of tissues identified in biodistribution studies to determine the biological and pathological consequence, if any, of vector presence.

• Transgene Expression and Immunogenicity: Utilization of immunohistochemistry (IHC) and in situ hybridization (ISH) to confirm on-target transgene expression and to characterize the nature and extent of any immune cell infiltration in both target and non-target tissues.

The assessment of host immune responses is a core component of any viral vector safety program. A multi-faceted approach is required to evaluate humoral, innate, and T-cell mediated responses. While systemic assays provide quantitative data, histology provides the indispensable anatomical context. By visualizing immune cell populations directly within tissues, we can differentiate between a productive immune response and undesirable immunotoxicity. This approach provides the clear, defensible evidence required by regulators and delivers rapid pathology insights accelerating preclinical readouts.

Our scientific framework is built upon the 3Rs principles: to Replace, Reduce, and Refine the use of animals in research. about our welfare programs.

Our teams operate within a >100,000 sq ft facility designed for advanced therapy programs. Since the Franklin Biolabs brand launch in 2024, programs we have supported have maintained a 100% IND success rate, a track record established by our core scientific team since 2019. We provide the specialized histology data needed to meet EMA expectations for lentiviral cell therapies.