CAR-T Cell Therapy Review

Comprehensive vocabulary flashcards covering the definitions, receptors, generations, mechanisms, and clinical challenges of CAR-T cell therapy as discussed in the lecture.

Immunotherapy

The treatment of a disease by activating the immune system to attack the diseased cells.

Autologous cells

Immune cells sourced from the host patient.

Allogenic immune cells

Immune cells sourced from a donor other than the host patient.

CAR (Chimeric Antigen Receptor) -T Cell

A T-cell engineered to express a synthetic receptor that allow it to change its specificity to target diseased cells.

HLA molecule

A molecule that presents tumour antigens to normal T-cell receptors consisting of alpha and beta chains.

Single chain variable fragments (scFvs)

The component of a CAR-T cell receptor that recognises tumour antigens in the absence of HLA.

CD3 zeta domain

A signalling domain in the CAR-T receptor that activates the T-cell when an antigen binds to the receptor.

First Generation of CAR-T Cell

A CAR-T cell containing only two domains: an antigen binding domain ($scFvs$) and a $\text{CD3}$ zeta for signalling.

Second Generation of CAR-T Cell

A CAR-T cell that includes an additional costimulatory domain, such as $\text{CD28}$ zeta or $4-1\text{BB}$ zeta, for proliferation and retained functionality.

CD28 zeta domain

A costimulatory domain that enhances T-cell proliferation for faster tumour elimination but results in a shorter duration of activation.

4-1BB zeta domain

A costimulatory domain that provides slower/weaker activation of T-cells but allows them to last longer and supports $\text{CD28}$ T-cell expansion.

Transduction

The process of introducing the CAR gene into isolated T-cells to allow the expression of the Chimeric Antigen Receptor.

Immune surveillance

The process by which $\text{CAR-T}$ cells persist in the body to continue monitoring for and detecting remaining or recurring tumour antigens.

CD19

A B-cell receptor expressed on the surface of all B-cells, often used as the target for treating haematological cancers like B-cell leukaemia.

Cytokine Release Syndrome (CRS)

A side effect of $\text{CAR-T}$ therapy caused by T-cells releasing cytokines, which can lead to tissue damage.

Neurotoxicity

A side effect of $\text{CAR-T}$ therapy that may occur due to increased immune responses leading to increased permeability of the Blood-Brain Barrier (BBB).

Tocilizumab

An $\text{anti-IL-6}$ receptor antagonist given as an immunosuppressant to control and manage Cytokine Release Syndrome (CRS).

Antigen escape

A mechanism of treatment tolerance where cancer cells stop expressing the target antigen (e.g., $\text{CD19}$) to evade the immune system.

T-cell exhaustion

A state where long-term activated T-cells lose effector functions and shut down, often mediated by the $\text{PD-1/PD-L1}$ pathways.

Checkpoint inhibitors

Immunotherapies that block exhaustion pathways like $\text{PD-1/PD-L1}$ to allow $\text{CAR-T}$ cells to remain activated for longer.

B-cell aplasia

A condition in $\text{CD19}$ targeting therapies where all B-cells, including healthy ones, are destroyed by the $\text{CAR-T}$ cells.

Retroviral vector

The tool used to engineer $\text{CAR-T}$ cells by integrating the CAR gene into the host genome.