Chimeric Antigen Receptor

Definition

A chimeric antigen receptor (CAR) is a synthetic receptor that is engineered by combining an antigen-binding domain, typically derived from an antibody, with signaling domains from T-cell receptors. This fusion allows T cells expressing the CAR to recognize specific tumor-associated antigens and mount an immune response against cancer cells.

5 Must Know Facts For Your Next Test

1. CARs are designed to target specific tumor-associated antigens, allowing T cells to recognize and eliminate cancer cells expressing those antigens.
2. The antigen-binding domain of a CAR is typically derived from a monoclonal antibody, which gives the T cell the ability to recognize its target independently of major histocompatibility complex (MHC) presentation.
3. CAR-T cell therapy involves genetically modifying a patient's own T cells to express the desired CAR, then expanding and infusing these cells back into the patient to mount an anti-tumor immune response.
4. The signaling domains within the CAR, such as CD3ζ and costimulatory domains like CD28 or 4-1BB, activate and sustain the T-cell response upon antigen recognition.
5. CAR-T cell therapy has shown promising results in the treatment of certain hematological malignancies, such as B-cell acute lymphoblastic leukemia and diffuse large B-cell lymphoma.

Review Questions

• Explain the key components of a chimeric antigen receptor and how they work together to enable T-cell recognition and activation against cancer cells.
  • A chimeric antigen receptor (CAR) is composed of an extracellular antigen-binding domain, typically derived from a monoclonal antibody, fused to intracellular T-cell signaling domains. The antigen-binding domain allows the CAR-T cell to recognize specific tumor-associated antigens on the surface of cancer cells, independent of major histocompatibility complex (MHC) presentation. The intracellular signaling domains, such as CD3ζ and costimulatory domains like CD28 or 4-1BB, then activate the T cell and sustain its anti-tumor immune response upon antigen recognition, leading to the elimination of the targeted cancer cells.
• Describe the process of CAR-T cell therapy and how it is used to treat certain types of cancer.
  • CAR-T cell therapy is a form of adoptive cell therapy that involves genetically modifying a patient's own T cells to express a chimeric antigen receptor (CAR). First, the patient's T cells are harvested and then engineered to express the desired CAR, which is designed to recognize a specific tumor-associated antigen. These CAR-T cells are then expanded in the laboratory and infused back into the patient, where they can recognize and mount an immune response against cancer cells expressing the target antigen. CAR-T cell therapy has shown promising results in the treatment of certain hematological malignancies, such as B-cell acute lymphoblastic leukemia and diffuse large B-cell lymphoma, by leveraging the patient's own immune system to eliminate cancer cells.
• Analyze the potential advantages and challenges associated with the use of chimeric antigen receptor (CAR) technology in cancer immunotherapy.
  • The key advantage of CAR technology in cancer immunotherapy is that it allows T cells to recognize and attack cancer cells independently of major histocompatibility complex (MHC) presentation, expanding the potential pool of targetable tumor-associated antigens. Additionally, the inclusion of potent T-cell signaling domains within the CAR can enhance the activation and persistence of the modified T cells, leading to more robust and durable anti-tumor responses. However, challenges with CAR-T cell therapy include the potential for on-target, off-tumor toxicity if the target antigen is also expressed on healthy tissues, the risk of cytokine release syndrome and neurotoxicity as a result of excessive T-cell activation, and the development of antigen-negative tumor escape variants. Ongoing research aims to address these challenges and further optimize the safety and efficacy of CAR-T cell therapies for cancer treatment.

Related terms

Adoptive Cell Therapy:

A type of immunotherapy that involves the transfer of autologous or allogeneic T cells that have been genetically engineered to express CARs, enabling them to recognize and attack cancer cells.

Tumor-Associated Antigen: Proteins or other molecules that are expressed at higher levels on the surface of cancer cells compared to normal cells, making them potential targets for CAR-T cell therapy.

T-Cell Receptor: A receptor complex found on the surface of T cells that recognizes specific peptide antigens presented by major histocompatibility complex (MHC) molecules, triggering T-cell activation and an immune response.