Important Advances in Using CAR T-Cell Immunotherapy for Organ Cancers

Chimeric antigen receptor (CAR) T cells have been strikingly successful in hematological (blood and bone marrow) cancers, but not yet effective against solid (organ) tumors. Two main reasons are easier access to cancer cells in the circulation in hematological cancers and organ cancers’ more complex tumor microenvironment.

In the video below, you can see how the living cancer drug CAR-T-cell treatment is prepared and administered (with Turkish subtitles).

However, CAR T-cell immunotherapies for solid cancers are under intensive investigation. A recent study by Samaha and colleagues presents a preclinical CAR T-cell therapy for glioblastoma brain tumors . In a glioblastoma mouse model, researchers genetically modified CAR T cells to first adhere to the inner blood vessel wall, then infiltrate the tumor outside the vessel.

Explanation of Figures 1 and 2: Activated leukocyte cell adhesion molecule (ALCAM) binds to a T-cell CD6 receptor . Stronger CD6-ALCAM binding was achieved by adding 5HS (Homing System) to CAR-T cells, facilitating T-cell passage across the blood-brain barrier into the central nervous system (brain). On CAR T-cell surfaces, HER2 molecularly targets cancer cells. CAR T cells thus use 5HS to leave blood vessels and HER2 to locate cancer cells. This cellular immunotherapy could rightly be called the smartest cancer treatment devised to date.

This homing system design is based on basic research into how cell-surface receptors regulate the immune system at the molecular level. CAR T-cell function in solid tumors faces many potential challenges, but similar rational approaches may make modified CAR T cells effective in different solid tumors, applied in combinations targeting molecular features.

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