Autologous T Cells Transduced With Retroviral Vector Encoding An Anti-CD-19 CD28/CD3-zeta Chimeric Antigen Receptor

Autologous T Cells Transduced With Retroviral Vector Encoding An Anti-CD-19 CD28/CD3-zeta Chimeric Antigen Receptor Uses, Dosage, Side Effects, Food Interaction and all others data.

Autologous T Cells Transduced With Retroviral Vector Encoding An Anti-CD-19 CD28/CD3-zeta Chimeric Antigen Receptor 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.

Autologous T Cells Transduced With Retroviral Vector Encoding An Anti-CD-19 CD28/CD3-zeta Chimeric Antigen Receptor
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Trade Name	Autologous T Cells Transduced With Retroviral Vector Encoding An Anti-CD-19 CD28/CD3-zeta Chimeric Antigen Receptor
Generic	Axicabtagene ciloleucel
Axicabtagene ciloleucel Other Names	Autologous T cells transduced with retroviral vector encoding an anti-CD-19 CD28/CD3-zeta chimeric antigen receptor, Axicabtagene ciloleucel
Type
Groups	Approved
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Last Updated:	September 19, 2023 at 7:00 am

Uses

Autologous T Cells Transduced With Retroviral Vector Encoding An Anti-CD-19 CD28/CD3-zeta Chimeric Antigen Receptor is a CAR T cell therapy for relapsed or refractory large B-cell lymphoma, diffuse large B-cell lymphoma, primary mediastinal large B-cell lymphoma, high grade B-cell lymphoma, and diffuse large B-cell lymphoma from follicular lymphoma.

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.

Autologous T Cells Transduced With Retroviral Vector Encoding An Anti-CD-19 CD28/CD3-zeta Chimeric Antigen Receptor is also used to associated treatment for these conditions: Refractory Diffuse large B-cell lymphoma NOS, Refractory High grade B-cell lymphoma Burkitt-like lymphoma, Refractory Primary Mediastinal Large B-Cell Lymphoma, Relapsed Diffuse large B-cell lymphoma NOS, Relapsed High grade B-cell lymphoma Burkitt-like lymphoma, Relapsed Primary Mediastinal Large B-Cell Lymphoma

How Autologous T Cells Transduced With Retroviral Vector Encoding An Anti-CD-19 CD28/CD3-zeta Chimeric Antigen Receptor works

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.

Autologous T Cells Transduced With Retroviral Vector Encoding An Anti-CD-19 CD28/CD3-zeta Chimeric Antigen Receptor 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.

Toxicity

Axicabatagene ciloleucel is reported to induce cytokine release syndrome (CRS) and neurotoxicity. No carcinogenicity or genotoxicity studies as well as reproductive toxicity studies have not been conducted with axicabatagene ciloleucel.

Food Interaction

No interactions found.

Elimination Route

Following infusion of YESCARTA, anti-CD19 CAR T cells exhibited an initial rapid expansion followed by a decline to near baseline levels by 3 months. Peak levels of anti-CD19 CAR T cells occurred within the first 7-14 days after YESCARTA infusion . The mean AUC in Day 0-28 in responding patient was 557.1 days x cells/μL .