On Monday, August 21, 2023, the Chinese biotech company CARsgen Therapeutics announced that it will enter a collaboration with the mRNA giant Moderna to combine their solid tumor CAR-T cell therapy and mRNA therapeutic cancer vaccine.
This is not the first time CAR-T cell therapy has been combined with another modality (AAV, Lentivirus, mRNA, etc.) for enhanced therapeutic effects. Today we’ll take a look at the CAR-T and mRNA technologies and how combining them can enhance the overall therapeutic effect. According to the agreement, the two programs that will be collaborated on are CARsgen’s Claudin18.2 CAR T cell candidate (CT041) and Moderna’s investigational mRNA cancer vaccine.
- What is Claudin18.2?
Claudins (CLDNs) are a family of tight junction proteins. CLDN18.2 is an isoform of CLDN18. It has highly limited expression in normal healthy tissues but is often overexpressed in primary malignant tumor cells. CLDN18.2 plays a critical role in the proliferation, differentiation, and migration of tumor cells. Due to its difference in expression levels between healthy and tumor cells, it has been chosen as a highly selective biomarker that can be widely used for the diagnosis and potential treatment of various tumors, such as gastric cancer/gastroesophageal junction (GC/GEJ) cancer, breast cancer, colon cancer, liver cancer, head and neck cancer, bronchial cancer, and non-small-cell lung cancer.
- What’s the mechanism of mRNA cancer vaccine?
mRNA can encode neoantigens as an immunotherapeutic tool for various cancers. Neoantigens are foreign proteins that are absent from healthy tissues but are expressed in tumors. After mRNA is administered into the body and enters cells, it will go through the translation process where neoantigen-encoding mRNA is translated into the neoantigens with the help of ribosomes. The neoantigens produced will then trigger the immune response and essentially train our immune system to better recognize and attack the proteins produced by potential cancer cells in the future. It’s like training a strong army to attack a known enemy troop in preparation for future wars.
- How does CAR-T cell therapy work?
CAR-T cell therapy is therapy using a patient’s own T cells (one type of white blood cells) to recognize and fight cancer cells. CAR stands for chimeric antigen receptor, which is a recombinant receptor used to redirect the specificity and function of T cells. The overall process of CAR-T involves: 1. collecting T cells from a patient and sending them to a specialized facility; 2) inserting the gene for CAR into the T cells at the specialized facility, which will express the CAR protein; 3) incubating the cells so they can grow into millions; 4) transferring the cells back to the patient so they can fight against cancer.
- What’s the benefit of combining CAR-T and mRNA vaccine for cancer treatment?
The combination of CAR-T cell therapy and mRNA-based vaccines represents a promising advancement in cancer immunotherapy. Dendritic cells (DCs) can uptake mRNA and translate it into neoantigens. Subsequently, T cells can bind to DCs and produce tumor-specific antibodies against cancer cells. It addresses limitations of conventional CAR-T therapy and harnesses the power of mRNA technology to boost CAR-T cell expansion, persistence, and antitumor activity while offering a versatile and adaptable approach to treating various types of cancers. The combination of the two also allows for a synergistic effect, where the CAR-T cells are not only equipped to directly attack cancer cells but are also supported by the immune-stimulating effects of the mRNA vaccines.