First clinical trials of brain cancer immune therapy succeed and account for individual genetic features

Main challenges in treating brain cancer patients are high risk of disease recurrence and death within 1-1.5 years after the tumor onset. Existing therapeutic technologies are based on stimulating the patient's immune system to fight malignant tumors, which is rarely effective enough and causes side effects.

A group of scientists has conducted a comprehensive study of the processes that help the immune system to attack brain cancer cells and save healthy tissue. The study is based on the fact that in some brain cancer patients disease developed extremely aggressive. Genetic testing of malignant tissues samples from these patients revealed mutation of the epidermal growth factor protein receptor (EGFRvIII). Such a mutation blocked standard immune therapy effect on tumor using T-cells developed to express the chimeric antigen receptor (CAR).

Initial scientific research was performed in laboratory mice and was objected to developing and testing antibodies that are able to selectively bind EGFRvIII surface-expressing cells. Scientists developed a range of antibodies called variable single-chain fragments (ScFv) and selected those that recognize mutated proteins and distinguish them from the normal EGFRs that are widely present on cells in the human body.

Second stage used genetic engineering methods, and mouse ScFvs were made similar to human ones and the analysis repeated. Humanized mouse single-stranded fragments were compared with their human-origin counterparts, and those fragments able to distinguish normal EGFRs from mutated were selected. Selected ScFvs were evaluated for their ability to transport T cells. It was revealed that EGFRIII engineered CAR T cells did not attack cells with normal epidermal growth factor receptors in animal models.

Within the next stage, anti-cancer efficacy of ScFv using human tumor cells was studied. EGFRvIII CAR T cells appeared to have the ability to multiply and release cytokines in response to the presence of a mutant protein on cancer cells and can control tumor growth. The administration of the obtained T cells comdined with chemotherapy temozolomide (which is used to treat patients with glioblastoma), caused the reduction or full elimination of experimental mice tumors.

As a result of these lab scientific studies, the investigators developed an immune drug based on ScFvs recognizing the EGFRvIII proteins. This drug was clinically studied in 12 brain cancer patients with different disease stages. The drug was effective and revealed no side effects.

Scientists are constantly improving the developed immune therapy before clinical use