Suicide Gene Therapy Solution for CRS Management

With more than ten years' experience in the CAR area, now Creative Biolabs is focused on drug discovery and development for cellular therapy. We are dedicated to bringing collaborative spirit during the whole process of our service. With the objective of serving better, our scientists have established innovative platforms about therapy discovery and development for CRS management.

Toxicities of CAR Modified T Cells

CAR-T cell therapies have developed to the forefront of cancer treatment approaches. Leverage by the natural immune system, the anti-tumor efficacy of CAR-modified T cells is greatly improved. As a double-edged weapon, the brisk immune system can help patients to fight with cancer after infusion of CAR-T cells but also can cause enhanced toxicities including cytokine release syndrome (CRS), anaphylaxis/allergy, and neurological toxicity. As one of the most promising treatment modality, CRS management (one type of the toxicities) become more and more important to improve the safety of CAR-T cell therapy.

Fig.1 Toxicities of CAR-modified T cells. (Sun, 2018)

Suicide Gene Therapy Solutions for CRS Management

In light of the various types of toxicities caused by the administration of CAR-modified T cells, it's necessary to find a balance between efficacy and safety. To achieve this, scientists all over the world have put forward several strategies. In Creative Biolabs, we have professional scientists who are versed in CAR-T cell therapy development. We provide suicide gene therapy solutions for CRS management. Suicide gene is a co-expressed molecule that can induce the selective destruction of CAR-T cells upon the administration of a nontoxic prodrug. Here are 3 strategies we provide. If you have any other specific requirements, please reach out to our scientists for assistance. We are committed to being the most trusted provider of drug discovery, development, and manufacturing solutions for biotech and pharmaceutical innovators.

• HSV-tk Suicide Therapy: The CAR-modified T cells will be eliminated upon being exposed to GCV.
• iCasp9 Suicide Therapy: Upon the administration of the synthetic molecule AP1903, the fusion protein (caspase 9 and a drug-sensitive protein) will dimerize, resulting in the rapid apoptosis of CAR-T cells.
• Targetable Surface Antigen Suicide Therapy: The CAR-T cells are transduced with targetable surface antigens such as CD20 or truncated EGFR. After the administration of the relevant monoclonal antibody (anti-CD20 mAb, or anti-tEGFR mAb), CAR-T cells will be eliminated through complement/antibody-dependent cellular cytotoxicity (CDC/ADCC).

Fig.2 Approaches of overcoming toxicities by the suicide gene co-expression in T cells. (Sun, 2018)

Highlight Features

• From discovery to animal model testing
• Comprehensive portfolio
• Support every step of the way

At Creative Biolabs, we are dedicated to accelerating your drug discovery and development programs from the early discovery to later in vivo animal validation. Our goal is to expedite your program and promote your drug candidate through the discovery pipeline faster. Any questions, please don't hesitate to contact us.

References

1. Khadka, Roman H., et al. "Management of cytokine release syndrome: an update on emerging antigen-specific T cell engaging immunotherapies." Immunotherapy. 11.10 (2019): 851-857.
2. Sun, Shangjun, et al. "Immunotherapy with CAR-modified T cells: Toxicities and overcoming strategies." Journal of immunology research. 2018 (2018).