Improved CAR-T cell therapy can treat solid tumors in children

Improved CAR-T cell therapy can treat solid tumors in children. Nature: “Improved” CAR T cell therapy can combat solid tumors in children.

Introduction: Scientists from Los Angeles Children’s Hospital published a paper in the journal Nature Communications. Scientists have developed an improved version of CAR T therapy, showing the promise of targeted therapy for neuroblastoma, which can preserve healthy brain tissue and kill cancer cells more effectively.

Recently, scientists from Los Angeles Children’s Hospital published a paper entitled “Preclinical assessment of the efficacy and specificity of GD2-B7H3 SynNotch CAR-T in metastatic neuroblastoma” in the journal Nature Communications. Scientists have developed an improved version of CAR T, which shows the hope of targeting neuroblastoma, which can preserve healthy brain tissue and kill cancer cells more effectively. Although this work is in the preclinical stage, it reveals the potential of life-saving treatments in children and adults with solid tumors.
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CAR-T therapy is chimeric antigen receptor T cell immunotherapy, which is a new type of precision targeted therapy for tumor treatment. In recent years, it has achieved very good results in clinical tumor treatment through optimization and improvement. A promising new tumor immunotherapy method that can be precise, fast, efficient, and possibly cure cancer.

There is a big difference between childhood cancer and adult cancer whether it is the cause of cancer or the type of cancer. Among childhood tumors, the most common is naturally not lung cancer, gastric cancer, etc., but neuroblastoma, especially those under 5 years old In children, neuroblastoma can account for 50% of all cancers, far exceeding the proportion of different cancers in adult cancers. So is there any new treatment?

In recent years, CAR-T cell therapy has opened up a new world in the field of advanced relapse and refractory B-cell tumors, and it has also shown the magic of this therapy. Recently, a group of scientists from Los Angeles Children’s Hospital developed the “CAR T Therapy Modified Version”, showing the hope of targeting neuroblastoma, which can preserve healthy brain tissue and kill cancer cells more effectively.

However, the treatment of solid tumors such as breast cancer or neuroblastoma poses a dilemma: Many antigens on their surface are still present in healthy tissues, and these tissues cannot safely manage toxicity like leukemia. In patients with solid tumors, treatment with CAR T cells will kill cancer cells and healthy tissues indiscriminately. Because of this suppressive immune environment in solid tumors, preclinical studies on these cancers have resulted in poor efficacy or unacceptable levels of toxicity.

The research team used a new CAR T technology called synthetic Notch (or synNotch). SynNotch CAR T cells have unique characteristics (called “gating”) that allow them to target specific cancers very precisely. The function of gating is similar to a tool often used by computer programmers: if condition A is met, operation B is performed.

Dr. Moghimi said: “The way it works is truly unique. The special synNotch protein on the surface of the T cell is designed to recognize the antigen GD2. When this happens, the synNotch protein instructs the T cell to activate its CAR T properties so that it can Recognize the second antigen B7H3. T cells must follow these specific instructions, which means that it can only kill cells that have both antigens.”

This “gating” feature is the key to minimizing toxicity. Healthy cells sometimes reduce the level of one of the antigens, but not at the same time. Solid tumors like neuroblastoma have both GD2 and B7H3 antigens. Dr. Asgharzadeh’s team has designed synNotch cells to recognize them.

The team also overcome another challenge.

Dr. Asgharzadeh said: “With normal CAR T treatment, CAR T cells will burn and become inactive after a period of time. However, we found that the metabolism of synNotch CAR T cells is more stable because they are not continuously activated. This means they Using less energy, this allows them to continue to fight cancer for a longer period of time.”

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