Engineered CAR-T Immune Cells Eliminate glioblastoma brain Cancer in Mice

Good news! Seems to be some very promising research results! There were actually several recent articles covering this subject! Some of the latest research is actually mutually reinforcing each other. Cancer is history!

"... In a pair of recently published studies in Science Translational Medicine,1,2 scientists showed that CAR T-cells are more effective when their killing activity is tied to two receptors: one that recognizes the tumor and another that recognizes a different aspect of either the tumor or the environment. These double-trouble CAR T cells have more precision and stamina, making them effective against many tumors that have not been successfully treated with CAR T cells before. ..."

"Two major hurdles in chimeric antigen receptor (CAR) T cell therapy for solid tumors are ensuring specificity to tumor cells without affecting healthy cells and avoiding tumor escape due to antigen loss. To address these challenges, Hyrenius-Wittsten et al. and Choe et al. developed synthetic notch (synNotch)–CAR T cells targeting solid tumor antigens and used them to treat mouse models of mesothelioma, ovarian cancer, and glioblastoma. In both studies, the authors demonstrated that synNotch-CAR T cells were better at controlling tumors than traditional CAR T cells and did not result in toxicity or damage to healthy tissue. ..."

"... Using CAR T cells isn’t a new approach, ... [researchers] took the method to the next level. They used a highly specific molecular approach—a human retained affinity screen—to make a single chain antibody and reconfigure it as a CAR. The resulting CAR, called GCT02, was long-lived and had a very high affinity for the epidermal growth factor receptor mutant variant III (EGFRvIII) found on brain tumor cells. ...
One challenge ... is that not all tumors express EGFRvIII. This means that some of the tumor cells could be left behind to grow after treatment.

... “We absolutely need to use combination therapies and be targeting multiple proteins, multiple tumor antigens at once. The heterogeneous nature of tumors like glioblastoma make them incredibly difficult to treat.” ..."

"... We use the human Retained Display (ReD) antibody platform (Myrio Therapeutics) to identify a novel single-chain variable fragment (scFv) that recognises epidermal growth factor receptor mutant variant III (EGFRvIII), a common and tumor-specific mutation found in glioblastoma ...
The epidermal growth factor receptor (EGFR) is an endogenous, growth-promoting cell surface protein and has been shown to be highly expressed in glioblastoma. EGFRvIII is the most common EGFR mutation in primary glioblastoma present in approximately 30% of newly diagnosed patients. ... exposes a therapeutically targetable binding region. Importantly, although the expression of EGFRvIII is highly heterogeneous and dynamic even within a tumor, its expression is restricted to malignant tissue. ..."

Engineered Immune Cells Eliminate Brain Cancer in Mice | The Scientist Magazine® Researchers developed a new CAR T-cell therapy that targets specific growth factor receptors in glioblastoma to eliminate brain tumors.

Environmental Cues Keep CAR T Cells on Track Pairing CARs with a synthetic receptor makes T cells more lethal tumor killers.

Here are the links to underlying research articles:

1. SynNotch-CAR T cells overcome challenges of specificity, heterogeneity, and persistence in treating glioblastoma (no public access)
2. SynNotch CAR circuits enhance solid tumor recognition and promote persistent antitumor activity in mouse models (no public access)
3. Novel high-affinity EGFRvIII-specific chimeric antigen receptor T cells  effectively eliminate human glioblastoma (open access)