Once a drug candidate has been identified and developed, safety and toxicity testing are critical next steps to ensure that no unexpected immune-related adverse events (IrAEs), such as cytokine release syndrome, are induced upon drug treatment.

Drug safety, also known as pharmacovigilance, involves assessing a drug's potential to cause harm. The aim is to identify, understand, and minimize adverse effects before the drug enters human trials. Selecting the appropriate preclinical model is crucial for ensuring that your results are translatable and mimic a human response.

If you have finished in vitro testing of your lead compound and are now seeking the most suitable in vivo preclinical model to evaluate your construct’s safety, genOway is here to support your next steps.

4 steps you need to follow for successful safety assessment of your compound

Relying on wild-type mice or inappropriate humanized models may result in a potentially viable drug candidate being rejected, or important adverse drug reactions not being detected, as occurred in the TeGenero 2006 clinical trial with TGN1412. This can happen when drug safety experiments are performed in PBMC-reconstituted mouse models that do not consider the contribution of myeloid cells to the elicited immune response and which contain a majority of pre-activated T cells.

当社は、お客様の研究ニーズに応えるため、幅広いトランスレーショナル前臨床モデルを開発しました。これらは単独で、あるいは相互に補完的に活用することで、研究効果を最大化し、研究を加速させることができます。これらのモデルは、すぐにご購入いただけます（当社の カタログ掲載モデル）で即座にご購入いただけるほか、お客様のご要望に合わせて特別に開発することも可能です（当社の カスタムモデル）のいずれかとなります。をご参照ください）。

Our selection of catalog models includes different types of models useful for safety assessment.

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ヒト化免疫系（HIS）モデル

As part of our catalog, we also provide humanized mouse models with a human immune system (HIS), such as the genO-BRGSF-HIS and genO-BRGSF-A2-HIS models. These models are engrafted with human CD34+ hematopoietic stem cells, which provide a much more complete reconstitution of the immune system compared to human PBMCs, thereby making them more translational to clinical studies. Given their functional human myeloid and lymphoid compartments, permissiveness to PDX and CDX engraftments, and extended lifespan, these models are ideal for safety assessment of immunotherapies targeting myeloid and lymphoid cells, as shown in articles published by both Sensei Bio and genOway.

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標的特異的なヒト化モデル

幅広い種類の 標的特異的なヒト化株が多数用意されており、今すぐご購入いただけます。これらのモデルは免疫能を有しており、ヒト標的遺伝子の生理的な発現を示します。当社のカタログに掲載されているモデルの一部は以下の通りです：

Several humanized immune checkpoint models, such as the genO-hCTLA-4 and the genO-hCD47/hSIRPα models, among many others. With these models you can assess the safety of your human-specific immunomodulators/immunotherapies. These models have proved successful in contributing to the safety testing of new therapies, as shown by Maxivax and Caedo Oncology.
Humanized CD3 and CD28 models are also available to help you assess the safety of new T-cell engagers, such as the genO-panhCD3 and genO-hCD28 models, as presented at the SITC 2022, and AACR 2024, respectively.
The humanized TFRC model (hCD71) allows you to test the safety of constructs aiming to cross the blood-brain barrier, or therapies targeting CD71-overexpressing cancers, as demonstrated by Bratti et al., 2024.
Our humanized FcγR model is a powerful tool for safety assessment of Fc-competent therapeutic antibodies.

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細胞株

Another important consideration when performing safety tests for cancer drugs is whether the tumor might impact the drug’s pharmacokinetics or mechanism of action, and whether the activation status of the immune system could also impact the drug’s safety profile. Therefore, if you would like to analyze the safety of your drug in a cancer biology context, our humanized mouse models can be used for syngeneic studies, for which a complementary catalog of cell lines is available.

A variety of cell lines, such as colon carcinoma cells lines (MC38 and CT26, for C57BL/6 and BALB/c mice, respectively) or a lymphoma cell line (EL4), are available.
これらの細胞株は、（EL4系統では）CD19や CD20などのヒトタンパク質を、あるいは（MC38およびCT26系統では）ヒト化免疫チェックポイントを発現するように改変されています。
また、当社はさまざまなレポーター細胞株およびノックアウト細胞株も提供しており、これらはお客様の有効性試験やターゲットの検証における対照としてご利用いただけます。

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免疫不全モデル

In our vast portfolio, you can also find immunodeficient rodents. These models can additionally be used for safety assessment in very specific cases. These include analyzing potential on- and off-target effects of CAR-T therapies or testing the safety of gene therapy. Our immunodeficient models support PDX and CDX engraftment and can develop metastasis, as well as allow longer experimental timeframes due to their extended longevity.