APR 25, 2024 8:00 AM PDT

Game-Changing New Receptor Unlocks the Potential of CAR-T Cell Therapy

WRITTEN BY: Amielle Moreno

Exciting cancer therapy innovations were announced in Cell Reports Medicine in the realm CAR-T-cell therapy (chimeric antigen receptor T cell). By designing a new cytokine receptor, Yoshikawa et al. of Keio University in Tokyo have elevate the efficacy and safety of CAR-T cell treatments to new heights.

Understanding the Challenge: Improving CAR-T Cell Therapy

CAR-T cell therapy has emerged as a transformative approach in treating B cell malignancies and multiple myeloma. However, this approach is in desperate need of refinement. While attacking tumor cells, CAR-T cell therapy is linked to safety issues like cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS).

Creating G6/7R: A Dual-Function Cytokine Receptor

In their groundbreaking study, Yoshikawa and colleagues engineered the G6/7R cytokine receptor to tackle these challenges head-on. This innovative receptor combines the extracellular domains of IL-6 receptor components with the intracellular signaling domain of IL-7 receptor, imparting dual functionalities crucial for improving CAR-T cell therapy outcomes.

Key Findings Unveiled by Yoshikawa et al.

The study demonstrated that G6/7R-expressing CAR-T cells possess remarkable capabilities. One standout feature is their ability to absorb and neutralize IL-6 produced by monocytes, a key player in CRS. This mechanism not only enhances the safety profile of CAR-T cells but also bolsters their antitumor effectiveness.

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Moreover, the constitutive IL-7 signaling within G6/7R-expressing CAR-T cells promotes their survival and proliferation, a critical factor for sustained therapeutic impact. In mouse models of both solid and liquid tumors, these cells exhibited robust expansion and prolonged persistence, particularly with a mutant called G6/7R-M452L showing enhanced proliferation.

Implications and Future Directions

The G6/7R cytokine receptor represents a versatile tool that could be applied across a spectrum of gene-engineered T cell therapies, offering hope for improved treatment outcomes across various cancers.

The engineering of G6/7R heralds an exciting new chapter in the evolution of CAR-T cell therapy. It underscores the transformative potential of innovative approaches to cancer treatment and sets the stage for further advancements in precision medicine.

Sources: Cell Reports Medicine

About the Author
Doctorate (PhD)
Amielle Moreno earned her doctorate in neuroscience from Emory University and has dedicated her career to science communication, news coverage, and academic writing/editing. She is a published researcher who has branched out to author articles for various science websites. She recently published an original research article detailing her findings on how sensory areas of the brain respond to social sound. When she's not writing or editing, you can find her spinning the latest neuroscience news into comedy gold, hosting her podcast "Miss Behavior Journal Club." This fortnightly humorous podcast features the latest in behavioral research. Her goal in life is to defend and discover scientific truths.
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