• One-Stop CAR-T Therapy Development
  • Biomarker Identification & Selection
  • ScFv Generation
  • CAR Design & Construction
  • CAR-T Gene Packaging & Delivery
  • Replication-Competent Virus Testing Services
  • CAR Cell In Vitro Assay
  • CAR-T Preclinical In Vivo Assay
  • IND Development for CAR-T Cell Therapy
  • GMP Production for CAR-T Products
  • CAR Clinical Trial
  • One-Stop Canine CAR-T Therapy Development
  • One-Stop mRNA CAR-T Therapy Development
  • TRAC-CAR-T Cell Development
  • Modular CAR-T Cell Generation
  • One-Stop Silence™ CAR-T Cell Development
  • Vaccine Boosting CAR-T Cell Therapy
  • STAb-T Cell Therapy Development
  • CAR-T Therapy Development in the Non-Cancer Field
  • Anti-HIV CAR Cell Therapy Development
  • T Cell Activity Modulator Discovery
  • T Cell Programming
  • Virus Specific T Cell (VST) Development
  • Antibody-Coupled T Cell Receptor (ACTR) Development
  • Organoid-induced hPSC-original T Cell Differentiation
  • γδ T Cell Engineering
• One-Stop TCR-T Therapy Development
  • TCR Biomarker Identification & Selection
  • TCR Generation & Optimization
  • TCR Design & Construction
  • TCR Gene Packaging & Delivery
  • TCR In Vitro Assay
  • TCR-T Preclinical In Vivo Assay
  • TCR Clinical Application
  • TCR Analysis
  • TCR Tetramerization Construction
  • ScFv-TCR T Cell Therapy Development
  • AbTCR Development
  • Bispecific TCR Development
  • CER Development
• One-Stop CAR-MA Therapy Development
• One-Stop CAR-NK Therapy Development
  • One-Stop CAR-NKT Therapy Development
  • One-Stop UniCAR-NK Therapy Development
  • iPSC-derived CAR-NK Therapy Development
  • One-Stop TCR-NK Therapy Development
  • NK Cell Genetic Engineering
  • NK Cell Expansion
• One-Stop CAR-B Therapy Development
• One-Stop CAR-Monocyte Therapy Development
• One-Stop Cytokine Release Syndrome (CRS) Management
• TCR-Like Antibody Development
  • MHC/Peptide Complex Production
  • TCR-Like Antibody Discovery
  • TCR-Like Antibody Affinity Characterization
  • TCR-Like CAR Construction & Evaluation
• In Vivo Cell Engineering Development
  • In Vivo CAR-T Cell Engineering
  • In Vivo B Cell Engineering
  • In Vivo CAR-NK Cell Engineering
  • In Vivo CAR-M Cell Engineering
• One-Stop Allogeneic Cell Therapy Development
  • Allogeneic CAR-T Therapy Development
  • Allogeneic TCR-T Therapy Development
  • Allogeneic CAR-NK Therapy Development
  • Allogeneic CAR/TCR Cell Design & Engineering
  • Other Allogeneic Cell Therapy Development
• TCR/CAR/Antigen-Engineered Tregs Development
  • CAR-Treg Development
• Cancer Vaccine Development
  • Cancer Vaccine Discovery
  • Cancer Vaccine Engineering
  • Cancer Vaccine Analytical Characterization
  • Cancer Vaccine In Vivo Assessment
  • Cancer Vaccine GMP Manufacturing
  • Dendritic Cell Vaccine Development
• Immune Genotyping
  • HLA Typing
  • KIR Typing
  • HLA Testing
  • Dog DLA Genotyping
  • Guinea Pig GPLA Genotyping
  • Mouse H2 Genotyping
  • Rabbit RLA Genotyping
  • Rat RT1 Genotyping
  • Rhesus Macaque MHC Genotyping
• Other Services
  • Tumor-infiltrating Lymphocyte-based Antibody Discovery
• TIL Therapy Development
  • Special TIL Therapy Development
  • One-Stop TIL Development
• CIK Therapy Development
  • One-Stop CIK Therapy Development
  • CIK Therapy Improvement
• Artificial T Cell-Stimulating Platform Development
  • Artificial T Cell Stimulator Development

IL-1R Blockade Discovery Service 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 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

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. 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.
3. 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.
4. Rooney, Cliona, and Tim Sauer. "Modeling cytokine release syndrome." Nature medicine 24.6 (2018): 705.
5. 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.