Two Science Sub-Journals: Smart Cell Therapy for the Treatment of Solid Tumors Released

Immunotherapy to fight cancer is a life-saving advancement for many patients, but this method is only effective for a few types of malignant tumors.

By "programming" basic computing power into immune cells (T cells) designed to attack cancer, these authors have overcome some major obstacles that still prevent these strategies from entering the clinic.

Glioblastoma is one of the most aggressive brain cancers affecting adults and children.

In the second paper, the authors discovered that the components of this system can be replaced like the head of a replaceable screwdriver to target difficult-to-treat cancers in other parts of the body.

In addition, these two papers have solved the so-called "T-cell exhaustion" problem, which is a long-standing challenge, that is, traditional CAR-T cells---in some of the most promising cancer immune systems.

Expanding immunotherapy to deadly brain cancer

Glioblastoma is a particularly tragic cancer.

Previous research work has identified a molecule that is often found on the surface of glioblastoma cells, which makes scientists hope that CAR-T cells can target this molecule to eliminate this deadly cancer.

Targeting other molecules will bring about the opposite but equally dangerous problems.

These authors designed a customizable solution to this problem by using a system called synNotch.

In order to kill glioblastoma, these authors adopted a novel two-step method.

The experiments described in the first paper show that this strategy is effective.

These authors stated that they should think of these cells as computers-smart enough to integrate multiple data points and make complex choices.

SynNotch is a flexible and powerful system for building smarter immunotherapy

The second paper further demonstrated the effectiveness of this method by identifying additional molecular targets for the synNotch system.

In the test of synNotch, which is designed to detect ALPPL2, CAR-T cells can accurately identify and kill mesothelioma and ovarian cancer cells.

A striking discovery of these two papers is that synNotch CAR-T cells maintain a stable level of activity throughout the process of killing cancer, eliminating the challenge of T cell exhaustion, and this exhaustion hinders traditional CAR-T therapy.

These authors found that, surprisingly, their synNotch system was not like this.

Reference materials:

Joseph H.
Choe et al.
SynNotch-CAR T cells overcome challenges of specificity, heterogeneity, and persistence in treating glioblastoma.
Science Translational Medicine, 2021, doi:10.
1126/scitranslmed.
abe7378.

Axel Hyrenius-Wittsten et al.
SynNotch CAR circuits enhance solid tumor recognition and promote persistent antitumor activity in mouse models.
Science Translational Medicine, 2021, doi:10.
1126/scitranslmed.
abd8836.

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