How are CAR T cells genetically engineered?

CAR T cells are a type of immunotherapy that uses genetically engineered T cells to target and destroy cancer cells. T cells are a type of white blood cell that plays a role in the body’s immune response. By genetically engineering T cells to express a chimeric antigen receptor (CAR), they can be redirected to target specific antigens on cancer cells.

The CAR construct

The CAR construct is a synthetic gene that encodes the CAR protein. The CAR protein consists of an extracellular antigen-binding domain, a transmembrane domain, and an intracellular signaling domain. The antigen-binding domain is designed to bind to a specific antigen on cancer cells. The transmembrane domain anchors the CAR protein to the T cell membrane. The intracellular signaling domain activates the T cell upon binding to the antigen, leading to the destruction of the cancer cell.

Gene transfer methods

There are two main methods for gene transfer into T cells: viral vectors and transposons.

• Viral vectors are viruses that have been modified to carry the CAR gene. When the viral vector infects a T cell, the CAR gene is integrated into the T cell genome. This method is efficient and can be used to transduce a large number of T cells.
• Transposons are pieces of DNA that can move from one location to another in the genome. Transposons can be engineered to carry the CAR gene. When the transposon is introduced into a T cell, it can randomly integrate into the T cell genome. This method is less efficient than viral vectors, but it is less likely to cause insertional mutagenesis.

Clinical trials

CAR T cells have shown promising results in clinical trials for the treatment of various types of cancer, including leukemia, lymphoma, and myeloma. However, there are still some challenges that need to be addressed, such as the development of resistance to CAR T cells and the potential for toxic side effects.

Conclusion

CAR T cells are a promising new immunotherapy for the treatment of cancer. However, there are still some challenges that need to be addressed before CAR T cells can be widely used in the clinic. Ongoing research is focused on improving the efficacy and safety of CAR T cells.

References

1. June CH, Sadelain M. Chimeric antigen receptor T-cell therapy for hematologic malignancies. N Engl J Med. 2018;379(1):33-44.
2. Sadelain M, Brentjens R, Rivière I. The basic principles of CAR T cell therapy. Cancer Discov. 2013;3(6):388-398.
3. Roybal KT, Zhang Y, June CH. Engineering T cells with chimeric antigen receptors: an update. Nat Rev Immunol. 2016;16(5):276-292.