IL-1R Blockade for CRS Management

All products and services are For Research Use Only and CANNOT be used in the treatment or diagnosis of disease.

At Creative Biolabs, our team is dedicated to working with you to design specific solutions and getting accurate results to facilitate your drug discovery and development programs. Empowered by cutting-edge technology and extensive experiences in T cell-engaging therapies, now we offer drug discovery and development services for IL-1R blockade therapies that can control the cytokine release syndrome (CRS) toxicities caused by T cell-engaging immunotherapies.

Background

Chimeric antigen receptor (CAR) therapy has emerged as an effective treatment for cancers, especially blood cancers. Even though a majority of patients achieve a good response following the infusion of CAR-T therapy, the application of this treatment is limited because CAR-T therapy is frequently related to life-threatening CRS and neurotoxicity. The hallmarks of severe CRS are characterized by high fever, hypotension, respiratory insufficiency, etc. which are related to elevated serum cytokines including IL-1, IL-6, GM-CSF. Studies have demonstrated that the CAR-T induced CRS is mediated by macrophages and it can be ameliorated by IL-1 or IL-6R blockade. These findings indicate that IL-1/IL-1R may be potential therapeutic targets to tackle CRS and neurotoxicity.

Fig.1 Blockade of IL-1 signaling. (Henderson, 2010)

IL-1R Blockade for CRS Management

Studies have demonstrated that monocyte-derived IL-1 is a major player for CRS and neurotoxicity caused by CAR-T therapy. Moreover, an anti-IL1R antagonist, anakinra can block the IL-1 function and mitigate the safety issues of CAR-T therapy as an immediately applicable approach. Furthermore, targeting IL-1 doesn't affect CAR-T cell antitumor activity. Based on these findings, IL-1/IL-1R was identified as the cause of CRS and neurotoxicity, and they may enable the development of safer CAR-T cells. At Creative Biolabs, we are dedicated to transferring the basic findings to novel drug development. With extensive experiences in CAR-T cell preclinical services, we are confident in providing excellent drug discovery and development services, and helping our clients to open new avenues to safer CAR-T cell therapies.

Fig.2 Blocking IL-1/IL-1R to inhibit CRS and neurotoxicity. (Rooney, 2018)

Highlights of IL-1/IL-1R Blockade

Blocking IL-1/IL-1R can attenuate cytokine release syndrome (CRS) without affecting the anti-tumor activity of CAR-T therapy.
Preclinical studies have demonstrated the CRS management effects.

Our Advantages

Advanced antibody discovery, engineering and manufacturing platforms
Integrated, multidisciplinary drug discovery expertise
One-stop solutions to save your time with competitive price

As a leading international partner of the scientific research institutes and biopharmaceutical companies, Creative Biolabs has accumulated extensive experiences in antibody drug discovery and development services, CAR-T construction and a series of preclinical services. We are dedicated to helping our clients develop promising drugs to manage the CRS caused by CAR-T therapy. If you are interested in our services, please feel free to contact us.

References

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.
Norelli, Margherita, et al. "Monocyte-derived IL-1 and IL-6 are differentially required for cytokine-release syndrome and neurotoxicity due to CAR-T cells." Nature medicine 24.6 (2018): 739.
Giavridis, Theodoros, et al. "CAR T cell–induced cytokine release syndrome is mediated by macrophages and abated by IL-1 blockade." Nature medicine 24.6 (2018): 731.
Rooney, Cliona, and Tim Sauer. "Modeling cytokine release syndrome." Nature medicine 24.6 (2018): 705.
Henderson, Cailin, and Raphaela Goldbach-Mansky. "Monogenic IL-1 mediated autoinflammatory and immunodeficiency syndromes: finding the right balance in response to danger signals." Clinical immunology 135.2 (2010): 210-222.