Repositioning Candidate Details
| Candidate ID: | R1501 |
| Source ID: | DB13915 |
| Source Type: | approved |
| Compound Type: | biotech |
| Compound Name: | Axicabtagene ciloleucel |
| Synonyms: | Autologous T cells transduced with retroviral vector encoding an anti-CD-19 CD28/CD3-zeta chimeric antigen receptor; Axicabtagene ciloleucel |
| Molecular Formula: | -- |
| SMILES: | -- |
| DrugBank Description: | Axicabtagene ciloleucel is a chimeric antigen receptor (CAR) T cell therapy for the treatment of Diffuse large B-cell lymphoma (DLBCL), which is a type of a non-Hodgkin lymphoma (NHL). It is the second cell-based gene therapy that is FDA-approved but the first in the treatment of large B-cell lymphoma in adult patients. Uniquely, axicabtagene ciloleucel utilizes each patient’s own immune system where each dose of the drug consists of the patient's genetically modified T-cells that were previously collected. The modified version of the T-cell expresses a new gene that targets and kills the lymphoma cells and is infused back into the patient. Diffuse large B-cell lymphoma (DLBCL) is the most common type of NHL in adults that mostly originates from the lymph nodes but can initiate outside of the lymphatic system. Lymphoma cells appear to be much larger in size than normal lymphocytes. In a multicenter clinical trial, the patients who were treated with axicabtagene ciloleucel achieved the complete remission rate of 51%. Developed by Kite Pharma, Inc., it was approved on October 18th, 2017 by the FDA as an intravenously infused anticancer therapy and is marketed under the brand name Yescarta. |
| CAS Number: | -- |
| Molecular Weight: | |
| DrugBank Indication: | Indicated for the treatment of adult patients with relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified, primary mediastinal large B-cell lymphoma, high grade B-cell lymphoma, and DLBCL arising from follicular lymphoma. |
| DrugBank Pharmacology: | The levels of cytokines, chemokines and other blood molecules were measured over a 4-week interval after the drug infusion. There were transient elevations of chemokines such as IL-6, IL-8, IL-10, IL-15, TNF-α, IFN-γ, and sIL2Rα where the peak elevation was reached within the first 14 days after infusion, and the levels gradually returned to baseline within 28 days . It is likely that axicabtagene ciloleucel may lead to B cell aplasia, or low numbers of B cells or absent B cells, as expected by other chimeric anntigen receptor T-cell therapies. |
| DrugBank MoA: | The CD 19 antigen is a 95 kDa integral membrane glycoprotein expressed on lymphocytes of the B-cell lineage but noton pluripotent stem cell. While this antigen is ubiquitously expressed on B lymphocyte lineage, the expression of this Ig protein is downregulated during terminal differentiation of premature and mature B cells into plasma cells . In blood disorders, however, the expression CD19 is maintained in in B-lineage cells that has undergone neoplastic transformation . Thus CD19 plays a critical role in clinical oncolgy as it aids in the diagnosis of blood cancers such as leukemias and lymphomas and serves as a therapeutic target for immunotherapies. Axicabtagene ciloleucel is a CD19-directed genetically modified autologous T cell immunotherapy that binds to CD19-expressing cancer cells and normal B cells. First, the patient's own peripheral blood mononuclear cells are obtained. The T cells are then harvested and genetically modified ex vivo by retroviral transduction to express a chimeric antigen receptor (CAR) comprising a murine anti-CD19 single chain variable fragment (scFv) linked to CD28 and CD3-zeta co-stimulatory domains . These anti-CD19 CAR T cells are expanded and infused back into the patient. Once the modified CAR T cells recognize the CD19-expressing target cells, the CD28 and CD3-zeta co-stimulatory domains activate downstream signaling cascades that lead to T-cell activation, proliferation, acquisition of effector functions and secretion of inflammatory cytokines and chemokines . These events lead to elimination of the target cells. |
| Targets: | B-lymphocyte antigen CD19 antibody |
| Inclusion Criteria: | Therapeutic strategy associated |
| Strategy ID | Strategy | Synonyms | Related Targets | Related Drugs | |
|---|---|---|---|---|---|
| S16 | Immunotherapy | -- | -- | -- | Details |
| S17 | Genetic therapy | Genetic approaches; genetherapy; Gene therapy | HSD17B13 inhibitor; PNPLA3-rs7 38409 (I148M) variant inhibitor; PNPLA3 expression down-regulator | INI-678; Momelotinib | Details |
| S05 | Anti-inflammatory | inflammatory | Bile acid; TNF-a inhibitor; Dual PPAR-α and -δ agonists; Toll-Like Receptor; (TLR)-4 antagonist; Caspase inhibitor; ASK-1 inhibitor | Ursodeoxycholic Acid; Pentoxifylline; Elafibranor; JKB-121; Emricasan; Selonsertib; | Details |
| S15 | Cell therapy | Mesenchymal stem cells; Stem cell therapy | -- | -- | Details |
| Diseases ID | DO ID | Disease Name | Definition | Class |
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