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Drug Discovery for Cytokine Release Syndrome (CRS) Management

With unrivaled expertise and experiences in various immunotherapy discovery and development, Creative Biolabs independently developed a novel generation of drug discovery platform to manage the severe cytokine release syndrome (CRS) caused by immunotherapies. Our scientists are dedicated to various mechanisms to discover sought-after and innovative approaches for precision medicine with CRS management capacity.

Background

Immunotherapies have immense potential to activate the inherent antitumor activities of the immune system to fight diseases. They have achieved unparalleled success in recent years, especially the chimeric antigen receptor (CAR) T therapy and bi-specific T cell engagers (BiTEs) therapy. Although the immunotherapies have been invested to improve the potency and efficacy, they are demonstrated to induce various degrees of toxicities, including cytokine release syndrome (CRS) and neurotoxicity syndrome. CAR-T and BiTEs therapies can result in acute toxicities - increased levels of pro-inflammatory cytokines in clinical use. In addition, T cells can produce granulocyte-monocyte colony-stimulating factor (GM-CSF) and IFN-γ. Furthermore, monocytes and macrophages can secrete IL-6 and IL-1β which contribute to further toxicities. For patients who were infused with CAR-T or BiTE therapies, they exhibit fever, vascular leakage and some degree of organ dysfunction, which are harmful to patients’ lives.

Drug Discovery for Cytokine Release Syndrome (CRS) Management

To move immunotherapies forward into the clinical stage, a balance between efficacy and toxicity management must be achieved. As a CRO to provide CAR-T therapy and therapeutic antibody discovery, our scientists have accumulated extensive experiences in immunotherapy discovery and development. With interdisciplinary efforts across scientists in Creative Biolabs, we have established one-stop platforms for various types of drug discovery for CRS management. Taken together, we aim to advance the innovative strategies to ameliorate toxicities associated with immunotherapies. Here are the major directions we focus on. If you are interested in any other approaches, please contact our scientists for further assistance.

Creative Biolabs has paid tremendous efforts in genetic engineering approaches to control the toxicity. We provide drug discovery solutions for our clients, including but not limited to CRISPR CAR, SUPRA CAR, inhibitory CARs, switch CARs, etc.

Creative Biolabs provides featured drug discovery solutions based on cytokine targeting approaches, including IL-6 and IL-6R antagonism, GM-CSF antagonism and IL-1 receptor antagonism.

Corticosteroids had been demonstrated to be valuable approaches to control the CRS when toxicities are refractory to other targeting therapies. Creative Biolabs offers drug discovery solutions to manage the CRS based on corticosteroids.

In consideration of the immunosuppressive effects on antitumor responses of immunotherapies caused by corticosteroids, small molecule inhibitors are also valuable approaches to control the aberrant intracellular signaling which contributes to the toxicities. Hence, Creative Biolabs also provides drug discovery solutions for small molecule inhibitor approaches.

Management of cytokine release syndrome and neurotoxicity associated with T cell engaging immunotherapies. Fig.1 Management of cytokine release syndrome and neurotoxicity associated with T cell engaging immunotherapies. (Khadka, 2019)

Highlight Features

  • Extensive experiences in immunotherapy discovery and development
  • Interdisciplinary efforts across scientists from various fields
  • Advanced one-stop drug discovery platforms

For ensuring the success of the promising and revolutionary therapies, Creative Biolabs launched a series of drug discovery services to manage the CRS. We are dedicated to providing new avenues to improve the toxicity management associated with your interested immunotherapies. Please feel free to contact us and our scientists will provide custom assistance for you.

Reference

  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.

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