In vivo Tumorigenicity Testing to Evaluate Your Therapeutics’ Safety

For all novel therapy types in the immuno-oncology field such as immunotherapies, small molecule, biologics, ATMPs, gene therapeutics etc., rigorous preclinical research is the key to success in clinical trials. Learn more about how InnoSer’s expertise in the oncology field helps you obtain relevant insights beyond examining the efficacy profile of your novel therapeutic candidates.  

Novel cell therapy products need to be evaluated for their potential to give rise to non-neoplastic and neoplastic lesions. This may especially be the case for therapies using human embryonic stem cells (hESCs) and induced-pluripotent stem cells (iPSCs). Contaminant undifferentiated cells within these cell cultures can form teratomas due to their intrinsic tumorigenic properties. InnoSer is part of a European grant project investigating HLA-homozygous iPSC-cardiomyocytE Aggregates to treat heart disease (HEAL). As part of the project, InnoSer perform in vivo biodistribution and tumorigenicity testing studies.  

Similarly, as part of one of InnoSer’s oncology research grant projects, our immuno-oncology team has worked with p53-deficient mice. Currently, p53 KO mice (p53-/- and/or p53+/-) are being explored by regulatory agencies to help reduce animal use and study duration of the required traditional two-year rodent carcinogenicity studies. In contrast to the heterozygotes, homozygous mice show a high susceptibility to cancer at younger ages already (Figure 1), resulting in a potentially more rapid tumorigenesis induction following treatment.  

FIGURE 1. Characterized spontaneous tumour incidences in the p53^-/- mouse model. Here, we evaluated the clinical onset of signs of disease (A) and survival probability (B) of the tP53 knockout mice  Kaplan-Meier curves show the time of onset of clinical signs and death. (C) Histopathological assessments have shown that most common spontaneous neoplasms were of skeletal, lymph node, spleen and liver-origin. Here shown as example images of spleen-originated tumours (arrow shows tumour cells, arrowhead points to necrosis). PanCK expression in the cytoplasm of cancer cells in spleen shows epithelial origin of the lesion. Lymph node originated tumours show neoplastic lymphocytes (H&E) which are CD3+ T-cells.

Drug development can be an iterative and long process, whereby InnoSer can be your dedicated partner, offering fast turnaround times with back-to-back experiments including PK/PD profiling to help you optimise your lead compounds. Curious to learn more about InnoSer’s capabilities within the drug development space?