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General Description:

Tisagenlecleucel, identified by CAS number 1823078-37-0, is a notable compound with significant therapeutic applications. Tisagenlecleucel is a CD19-directed genetically modified autologous T cell immunotherapy, or a CAR-T cell therapy for B-cell acute lymphoblastic leukemia. It was granted approval by FDA in August 2017 under the market name Kymriah. Tisagenlecleucel is an immunocellular therapy that involves autologous T cells that are collected from each individual patient and genetically engineered to express a specific protein called a chimeric antigen receptor (CAR) that specifically target CD19 antigens. Modified T cells are infused back into the patient's body. These CD19-directed chimeric antigen receptors (CD19 CAR-T cells) direct the T cells to target and kill leukemia cells that express CD19 on the cell surface. In a multicenter clinical trial involving pediatric and young adult patients with relapsed or refractory B-cell precursor ALL, the overall remission rate within three months of treatment was 83 percent.

Indications:

This drug is primarily indicated for: Tisagenlecleucel is indicated for use in individuals aged 25 years and younger with B-cell precursor acute lymphoblastic leukemia (ALL) that is refractory or in second or later relapse. It is also used to treat adult patients with relapsed or refractory (r/r) large B-cell lymphoma after two or more lines of systemic therapy including diffuse large B-cell lymphoma (DLBCL) not otherwise specified, high-grade B-cell lymphoma, and DLBCL arising from follicular lymphoma. Tisagenlecleucel is also indicated in adult patients with relapsed or refractory follicular lymphoma after two or more lines of systemic therapy. Its use in specific medical scenarios underscores its importance in the therapeutic landscape.

Absorption:

The absorption characteristics of Tisagenlecleucel are crucial for its therapeutic efficacy: In pediatric and young adult relapsed/refractory B-cell acute lymphoblastic leukemia (ALL) patients receiving tisagenlecleucel infusion, the mean peak plasma concentration was approximately 34,700 copies/mcg with a median time of 9.91 days to reach this value (Tmax). The drug's ability to rapidly penetrate into cells ensures quick onset of action.

Half-life:

The half-life of Tisagenlecleucel is an important consideration for its dosing schedule: The mean half life was 16.8 days in pediatric and young adult relapsed/refractory B-cell acute lymphoblastic leukemia (ALL) patients. This determines the duration of action and helps in formulating effective dosing regimens.

Volume of Distribution:

Tisagenlecleucel is distributed throughout the body with a volume of distribution of: The drug is found to be distributed in the blood as well as the bone marrow. Blood to bone marrow partitioning suggested that tisagenlecleucel distribution in bone marrow was 44% of that present in blood at Day 28 while at Months 3 and 6 tisagenlecleucel distributed at 67% and 69%, respectively, indicating high distribution to bone marrow. This metric indicates how extensively the drug permeates into body tissues.

Pharmacodynamics:

Tisagenlecleucel exerts its therapeutic effects through: Tisagenlecleucel demonstrates efficacy in re-inducing remission in patients with refractory B-cell precursor acute lymphoblastic leukemia. The sole purpose of the therapy is to eliminate CD19-expressing malignant and normal cells with specificity and increased chance of remission. The drug's ability to modulate various physiological processes underscores its efficacy in treating specific conditions.

Mechanism of Action:

Tisagenlecleucel functions by: Tisagenlecleucel is a CD19-directed genetically modified autologous T cell immunotherapy that involves genetically modified autologous T cells isolated from each individual patient. The reprogramming of the patient's T cells uses a lentiviral vector to encode an anti-CD19 chimeric antigen receptor (CAR). The CAR is comprised of a murine single-chain antibody fragment (scFv) specific for CD19, followed by a CD8 hinge and transmembrane region that is fused to the intracellular signaling domains from 4-1BB (CD137) and CD3 zeta. These intracellular costimulatory signaling domains increase the expansion, longer-term persistence and potency of CAR T cells; the CD3 zeta component is critical for initiating T-cell activation and antitumor activity, while 4-1BB enhances the expansion and persistence of tisagenlecleucel. Upon binding to CD19-expressing cells, the CAR transmits a signal to promote T-cell expansion, activation, target cell elimination, and persistence of the tisagenlecleucel cells. This mechanism highlights the drug's role in inhibiting or promoting specific biological pathways, contributing to its therapeutic effects.

Toxicity:

Categories:

Tisagenlecleucel is categorized under the following therapeutic classes: Amino Acids, Peptides, and Proteins, Antineoplastic Agents, Antineoplastic Agents, Immunological, Antineoplastic and Immunomodulating Agents, Cancer immunotherapy, CD19 Receptor Interactions, CD19-directed Chimeric Antigen Receptor, Genetically-modified Autologous T Cells, Immunotherapy, Membrane Proteins, Proteins, Receptors, Antigen. These classifications highlight the drug's diverse therapeutic applications and its importance in treating various conditions.