CAR-T-Cell-Based-Immunotherapy-Clinical-Applications-and-Challenges

CAR-T CELL-BASED IMMUNOTHERAPY CLINICAL APPLICATIONS AND CHALLENGES Tisagenlecleucel (Kymriah®) 1 Approved CAR-T therapies and Axicabtagene ciloleucel (Yescarta®) are currently the Developer US approval EU approval US approval Developer only two approved CAR-T therapies both in the United Indications August August October Indications States (US) and in the ALL 2017 2018 2017 DLBCL European Union (EU) for the PMBCL treatment of acute lympho- DLBCL Target blastic leukaemia (ALL), CD19 diffuse large B-cell lymphoma (DLBCL), and primary medi- 2 Representative CAR-T therapies in development astinal large B-cell lymphoma (PMBCL). They both target Product Developer Target(s) Indication(s) the B-lymphocyte antigen CD19. JCAR017 Juno Therapeutics/Celgene CD19 B cell NHL (DLBCL) UCART19 Cellectis/Pfizer CD19 B cell ALL Cytokine release syndrome bb2121 Bluebird bio BCMA Multiple myeloma LCAR-B38M Nanjing Legend Biotech BCMA Multiple myeloma (CRS) is the main toxicity KITE-585 Kite Pharma/Gilead Sciences BCMA Multiple myeloma AUTO2 Autolus BCMA and TACI Multiple myeloma associated with CAR-T thera- MB-102 Mustang Bio CD123 AML and BPDCN UCART123 Cellectis CD123 AML and BPDCN py and results from the CD33-targeted CAR Ziopharm Oncology (Intrexon) CD33 AML BPX601 Bellicum Pharmaceuticals PSCA Pancreatic cancer overproduction of inflammato- JCAR020 Juno Therapeutics MUC16 Ovarian cancer CAR-EGFR/EGFRvIII T CARsgen Therapeutics EGFRvIII Glioblastoma ry cytokines. These cytokines, MB-101 Mustang Bio IL-13Rα2 Glioblastoma JCAR023 Juno Therapeutics L1CAM Neuroblastoma such as TNF-α and IL-6, are Gastric/pancreatic CAR CLD18 T cells CARsgen Therapeutics Claudin-18.1 adenocarcinoma produced when CAR-T cells Glioblastoma proliferate in vivo, indirectly AU105 Aurora Biopharma HER2 and CMV activating macrophages and other cells of the immune system. Depending on the level of cytokine production, the clinical manifestations of CRS range from flu-like symp- toms to life-threatening shock. To mitigate this risk, cytokine signaling inhibitors such as Actemra® (tocilizumab), an IL-6 receptor antagonist, have 3 Challenges and countermeasures been repurposed to treat CRS when it occurs as a result of Tumor antigen Anti-tumor signal CAR-T therapy. “On-tar- IL-1 TNF-α get/off-tumor” toxicity is the Cytokine release syndrome other main side effect, which CD40 occurs when the CAR-T cells attack non-tumor cells that IL-6 Macrophage express the intended target CAR CD40L antigen. As a consequence, Cytokine signaling inhibitors CAR-T cell the patient is unable to make Tumor cell antibodies and becomes more CD19 susceptible to infection by On target/off tumor effects microorganisms. Novel CAR constructs, such as the fourth generation which is engineered with an inducible expression unit, can effective- Malignant B cell CAR-T cell Normal B cell Novel CAR constructs ly overcome the “on-target, off-tumor” drawbacks. WHAT WE DO: Creative Biolabs One-Stop CAR-T Therapy Development Services Products: CAR/TCR-related TCR Modified T Cell Development Services Diseases Associated Antigen Products & TCR-Like Antibody Services CAR Vector System Services Dendritic Cell Vaccine Development Services Viral Particle Bispecific TCR Development Service CAR/TCR Development Kits Copyright © 2018 Creative Biolabs. All Rights Reserved. | Contact Us