Genetic Engineering Publications - GEG Tech top picks

Currently, too few CAR T cells become memory cells that persist and create more T cells in the long term. However, a group of researchers recently showed that the distribution of the c-Myc protein in a parental T cell may be important for this process and published this work in the journal Nature. The researchers knew that a daughter cell with more c-Myc became an effector cell. In this study, the team found that the protein complex cBAF (canonical Brg1/Brg-associated factor) interacted with c-Myc. Daughter cells with high concentrations of cBAF and c-Myc became effector T cells. The cBAF binds certain regions of chromatin, proteins on DNA. The discovery suggests that it can guide the fate of cells, what type of T cells they become, by controlling the expression of effector cell-related genes. The distribution of cBAF occurs in the first activated T cell that begins the adaptive immune response; therefore, the researchers realized that cell fate is decided early in the immune response. The researchers used the molecular information they discovered. They applied a cBAF inhibitor during CAR T cell activation to generate more memory T cells. In a preclinical model, T cells treated with an inhibitor-controlled tumor growth better than untreated cells. The treated cells also survived longer and in greater numbers.

Pancreatic ductal adenocarcinoma (PDAC) is the most common type of pancreatic cancer and has the lowest survival rate of all common cancers. Only about 7% of people diagnosed with this type of cancer in the UK survive their cancer for 5 years or more. However, a new protein called CEACAM7 has been identified by researchers at Queen Mary University. It could be a new therapeutic target for the treatment of PDAC which is the most common type of pancreatic cancer. In this study, the researchers developed a novel CAR T cell therapy using part of an anti-CEACAM7 antibody from Professor Brad Nelson (British Columbia, Canada). They then modified the killer T cells and presented on their surface this new CAR protein that recognizes and binds to CEACAM7, directing the killer T cells to kill only the cells with CEACAM7. Using this protein as a target, the researchers were able to create a CAR T cell therapy that killed pancreatic cancer cells in a pre-clinical model.  

The CAR T-cell therapy idecabtagene vicleucel (ide-cel; Abecma) continues to demonstrate improved survival in heavily treated patients with relapsed/refractory multiple myeloma, according to updated results from the phase 2 KarMMa trial (NCT03361748) presented at the

2021 ASCO Annual Meeting. During the trial, 140 patients with at least three prior lines of treatment for multiple myeloma who were refractory to their last treatment regimen were enrolled. However, only 128 patients received an ide-cel infusion. The overall response rate was 73% in the overall population, with 33% complete response, 20% very good partial response and 20% partial response. The median time to first response was 1 month, with a median time to complete response of 2.8 months. In addition, the rapid response rate did not vary with the number of prior treatments received. The safety profile of ide-cel was consistent with long-term follow-up, with similar rates of infections and secondary primary malignancies, and no unexpected gene therapy-related toxicities were observed.