This article has been reviewed according to Science X's editorial process and policies. Editors have highlighted the following attributes while ensuring the content's credibility: By turning a patient's own immune cells into stronger cancer-fighting cells, CAR T-cell therapy has transformed how some blood cancers are treated. But it's been harder to extend this approach to solid tumors, including cancer that has spread to the bone.
Daniel Abate-Daga, Ph.D., associate member of the Department of Immunology and scientific director of the Cell Therapies and Gene Engineering Facility at Moffitt Cancer Center, leads a research team whose mission is to uncover the biological processes that prevent CAR T cells from achieving their full potential in solid tumors and to engineer new and more efficacious treatments. As part of that effort, the team developed a CAR T-cell treatment designed specifically to treat bone-metastatic prostate cancer. This treatment takes advantage of the unique biological properties of one specific type of T lymphocyte: gamma-delta T cells.
Unlike the conventional alpha-beta T cells used in all the FDA-approved CAR T treatments, gamma-delta T cells can interact with other medications administered to patients with bone-metastatic cancers, leading to increased potency without compromising safety. Now, the team has investigated new ways to improve upon that CAR T therapy, and they did so by carefully studying the biology of both types of white blood cells: alpha-beta and gamma-delta T cells. The study, published in Cellular and Molecular Immunology, used human T cells and cancer cells and mouse models, including prostate cancer that had spread to bone, to test how well these genetically engineered cells would do in a patient.
The researchers prepared both types of T cells with the same chimeric antigen receptor, or CAR. A CAR is a genetically engineered protein placed on the surface of a T cell that helps the cell recognize a target molecule on a cancer cell and activate the T cell to attack it. While the researchers found no significant difference in how effective the two types of cells were at killing cancer cells, the cells differed in several important ways.
One involved immune signaling. Gamma-delta CAR T cells produced fewer signaling molecules, including interferon-gamma, tumor necrosis factor-alpha, granzyme B and interleukin-2, which help carry out immune responses. Lower levels might mean fewer inflammatory side effects associated with CAR T therapy.
However, that prospect would have to be examined in future studies. Second, the researchers found differences in how the two types of cells use energy (metabolism). Gamma-delta CAR T cells produced and used energy more slowly than alpha-beta cells, which may help explain their lower production of some immune-signaling molecules.
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