Genetic Engineering Publications - GEG Tech top picks

Axi-cel CAR T therapy targets the CD19 molecule on large B-cell lymphoma cells. The ZUMA-7 trial demonstrated that axi-cel reduced the risk of disease progression, need for retreatment or death by 60% compared with standard therapy. Despite these positive results in terms of event-free survival and overall survival, some patients did not respond well to treatment or relapsed rapidly after treatment. Researchers analyzed tumor gene expression patterns from patient samples and determined that a B-cell gene expression signature and CD19 protein expression were significantly associated with improved event-free survival for patients treated with axi-cel but not with standard therapy. Patients with lower tumor cell levels of CD19 showed gene expression patterns associated with immunosuppression. These observations suggest that the tumor immune environment may play an important role in regulating axi-cel treatment and outcome. Furthermore, biomarkers associated with improved axi-cel treatment outcomes decreased as patients received more treatments, suggesting that receiving axi-cel as part of earlier treatment lines is essential to ensure better patient outcomes.

Chlorotoxin derived from scorpion venom has previously been shown to bind glioblastoma cells. Wang et al. designed a chimeric antigen receptor (CAR) based on chlorotoxin to surmount limitations of other glioblastoma-targeted CARs that have not been able to overcome tumor heterogeneity and antigen escape. They demonstrated that chlorotoxin binding captures a broader array of primary tumors than staining for previously identified antigenic targets. Chlorotoxin-directed CAR T cells were safe in mice and induced regression of orthotopic glioblastoma xenografts with no evidence of antigen escape. These toxin-based CAR T cells are distinct from conventional CAR design and could one day be used to deliver a poisonous blow to glioblastoma.

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.

In this study, the authors identified dasatinib as a drug that can temporarily inactivate CAR T cells to help reduce acute toxicity, allowing the T cells to recover their antitumor effects after the drug is withdrawn.