15 articles
Why do CAR-NK therapies work… until they don’t? This post looks at a paper by the Rezvani Lab that argues relapse isn’t just the tumor getting smarter, but immune cells slowly running out of energy.
The Rezvani lab identifies CREM, a transcription factor downstream of cAMP, as a checkpoint that CAR-NK cells install on themselves.
This paper tackles a problem that gets less attention than killing: how to get engineered T cells into immune-excluded tumors in the first place.
This paper made me think differently about T-cell metabolism because it argues that one small metabolite, phosphoenolpyruvate, can directly shape signaling and antitumor function.
Solid tumors have resisted both CAR-T therapy and antibody-drug conjugates for different reasons. This study collapses that divide, engineering CAR-T cells that deliver chemotherapy directly within the tumor microenvironment.
This preprint treats one of solid-tumor CAR-T’s biggest problems as a movement problem, engineering “velocity receptors” that push T cells into a more migratory state and improve infiltration, tumor control, and survival in preclinical models.
The field's response has been to engineer around each of them — dual targeting, chemokine receptors, armored constructs, TGF-β resistance. That work is real and this Perspective covers it.
This mini-review is less about a single experiment and more about building a translational map for risankizumab, tying IL-23 biology to dosing, pharmacokinetics, biomarkers, and pivotal efficacy data across psoriasis, psoriatic arthritis, and Crohn’s disease.
This paper argues that tumors do not only evade immunity with checkpoints and suppressive ligands. They may also win by taking the fuel first.
In a phase 2 study of mismatch repair-deficient locally advanced rectal cancer, single-agent dostarlimab produced a clinical complete response in every evaluable patient reported, with no patient proceeding to chemoradiotherapy or surgery during the follow-up window.
This paper helped define intratumoral T-cell dysfunction as a mitochondrial problem, not just an exhaustion-marker problem.
The design question becomes which two antigens, and the engineering question becomes how to fit two binders onto a cell — tandem scFvs, bicistronic vectors, two separate CARs.
This paper is one of the clearest demonstrations that long-term remission after CAR T therapy is not just about expansion. It is about persistence, cell state, and the kind of T cell that survives.
The intuitive assumption is that antigen-low relapse is the same process caught early — a tumor on its way to antigen-negative, or a subclone that always expressed less CD19 being selected. This paper argues the tumor is not doing anything.
This is not a data-heavy paper in the usual sense, but it may be one of the most useful conceptual frameworks in modern immuno-oncology.