Difference Between CAR-T and TCR-T

The key difference between CAR-T and TCR-T depends on the recognition of antigens. CAR-T is a form of therapy that recognizes the peptide antigens of cells to initiate an immune response while TCR-T is a form of therapy that recognizes the MHC molecules to initiate an immune response.

Immunotherapy is an important aspect of diagnostics. There are different forms of immunotherapy used in treating different forms of cancer, such as leukaemia. CAR-T stands for chimeric antigen receptor T cell therapy while TCR-T stands for T cell receptor therapy. They are two immunotherapies related to cancer therapy. Both CAR-T and TCR-T rely on the theory of antigen binding to the T cells. However, they differ in their recognition and action properties.

CONTENTS

1. Overview and Key Difference
2. What is CAR-T 
3. What is TCR-T
4. Side by Side Comparison – CAR-T vs TCR-T in Tabular Form
5. Summary

What is CAR-T?

CAR-T, which stands for Chimeric Antigen Receptor T-cell therapy, is a type of immunotherapy used against cancer cells or to attack cancer cells. They also refer to living drugs in the therapy of cancer. The basis of CAR-T is T lymphocytes. T lymphocytes are a type of major immunological cells that possess the cytotoxicity and kill cells. Therefore, they play a key role in producing immune responses. CAR-T involves the genetic engineering of the natural T cells. It will result in producing receptors on the T cell; these receptors are known as chimeric antigen receptors (CARs). These receptors are synthetic. Their production takes place under in vitro conditions.

After producing genetically engineered CARs, the CARs are incorporated into the T cells. It happens via different transformation techniques. Then the CARs-bound T cells will undergo cell proliferation. Proliferation only happens in successfully engineered T cells. Once the genetically modified cells proliferated, they are ready to be used in cancer therapy, especially against leukaemia. Once CAR-T cells reach the bloodstream, they will recognize the antigens on the tumour cells, and they will target the cells that have to be destroyed by the immune system.

However, the CAR-T type of therapy can also result in the destruction of healthy cells. It is one of the major disadvantages of this therapy.

What is TCR-T?

T lymphocytes are the main cells that can initiate an immune response against cancer cells, resulting in the cytotoxic killing of the cancer cells. T cell receptors recognize cancer cells. In the case of T cell Receptor therapy or TCR-T, the modification of the natural T cell receptors takes place in order to recognize the MHC molecules bound to cancer cells. Therefore, the TCR can recognize the intracellular antigens as well. Also, it makes TCR-T therapy more specific than CAR-T therapy.

Moreover, due to this special modification of the T cell receptor, the T cells become more specific. Hence, it enhances the affinity of TCR-T towards malignant cells. These high-affinity TCRs can then incorporate into the host immune system and then function to produce an immunogenic response. However, this form of immunotherapy is still under the stage of clinical trials.

What are the Similarities Between CAR-T and TCR-T?

• CAR-T and TCR-T are forms of immunotherapy.
• Both processes rely on antigen recognition.
• Also, both therapy forms have the ability to release cytokines in response to recognition.
• Moreover, they are used in cancer treatment.

What is the Difference Between CAR-T and TCR – T?

The key difference between the CAR-T and TCR-T depends on the type of modification made on the receptors in order to recognize a foreign cell. Thus, in this context, the CAR-T will identify surface antigens and initiate the immune response, whereas TCR-T will identify MHC bound cells to initiate the immune response. Moreover, a further difference between CAR-T and TCR-T is the specificity. That is; the specificity is higher in TCR-T in comparison to CAR-T. Besides all, only CAR-T is in the process of therapy, whereas TCR-T is still in the process of clinical trials.

The below info-graphic presents more information regarding the difference between CAR-T and TCR-T.

Summary – CAR-T vs TCR – T

Immunotherapy is an upcoming form of therapy, especially in the field of cancer prevention and therapy. The two forms of immunotherapy known as CAR-T and TCR-T rely on the T cell activity of the immune system. Chimeric antigen receptors bound to T cells can recognize surface antigens or fragments of antigens. Following recognition, they release signalling cascades to destroy the cells. In contrast, modified T cell receptors specifically bind to cancer cells presented with MHC molecules form the basis of TCR-T. Thus, this summarizes the difference between CAR-T and TCR-T.

Reference:

1. Harris, Daniel T, et al. “Comparison of T Cell Activities Mediated by Human TCRs and CARs That Use the Same Recognition Domains.” Journal of Immunology (Baltimore, Md. : 1950), U.S. National Library of Medicine, 1 Feb. 2018, Available here.

Image Courtesy:

1. “CAR-Engineered T-Cell Adoptive Transfer” By Caron A. Jacobson and Jerome Ritz –  (Public Domain) via Commons Wikimedia
2. “TCRComplex” By Anriar~commonswiki assumed (based on copyright claims) – Own work assumed (based on copyright claims) (CC BY-SA 3.0) via Commons Wikimedia