Supercharging CAR T Cell Therapy: A Step Toward Longer-Lasting Cancer Remissions

CAR T cell therapy has redefined what’s possible in cancer treatment, achieving remarkable responses in patients with blood cancers. Yet, a central challenge remains: these engineered T cells can lose strength over time, leading to relapse in diseases like multiple myeloma.

A recent Nature study offers a compelling path forward. By applying in vivo CRISPR screening—an approach that tests dozens of genetic edits in parallel—researchers identified molecular “brakes” that limit CAR T cell durability. Among them, one gene stood out: CDKN1B, a regulator of the cell cycle that restrains T cell proliferation.

When CDKN1B was removed, CAR T cells demonstrated striking improvements. They expanded more robustly, maintained cytotoxic function under repeated stimulation, and persisted longer in preclinical myeloma models. Importantly, CAR T cells engineered from patient samples showed the same advantage, pointing to a strategy that is both scientifically rigorous and clinically relevant.

For the field, these results underscore the potential of integrating functional genomics into CAR T design. Targeted genetic modifications such as CDKN1B deletion could extend the therapeutic window of CAR T therapy—transforming it from a treatment that induces remission into one that sustains it.

The takeaway is clear: CAR T therapy is not only powerful today, it is poised to become even more durable and effective tomorrow. With discoveries like this, the vision of long-lasting, relapse-resistant cell therapies is moving closer to clinical reality.

Reference:

Knudsen, N.H., Escobar, G., Korell, F. et al. In vivo CRISPR screens identify modifiers of CAR T cell function in myeloma. Nature (2025). https://doi.org/10.1038/s41586-025-09489-8