![]() Many other cancer patients have been treated with CAR T therapy since 2010, yet few have experienced these lasting results. “Ten years on, no leukemia cells, and we still have CAR-T cells that are on patrol and surveillance from leukemia” (Dr. ![]() However, the question remained-for how long? Could the CAR T cells persist, even in the eventual absence of cancer antigen? If they did, why? These early observations were hopeful, suggesting a mixed population of central and effector memory T cells could support CAR T-cell persistence (5). Multicolor flow cytometry was used to functionally characterize the CAR T cells, revealing unique compartments of CD4 + cells that appeared to acquire features of a central memory phenotype-T cells in a naive-like state, yet sensitive to cancer antigen stimulation (6)-and CD8 + cells with a strong effector memory profile, meaning they had experienced prolonged and robust exposure to antigen. Initial observations of the treatment in 2010 showed potent antileukemic effects in the patients, with quantitative PCR assays detecting expansion of CAR T cells and persistence in the blood and bone marrow for at least 6 months after treatment (5). CREDIT: ĬAR T cells are T cells taken from the patient’s own body and engineered to express a synthetic receptor known as a CAR, or chimeric antigen receptor, enabling a targeted attack against cancer cells once the T cells are reintroduced into the body (3, 4). #Timeplus com trial#Evolution of CAR T, a living therapyĪ recent example of this surprising feature of the drug development process comes out of a study of the long-term efficacy of the first ever CAR T-cell infusions (2), a cancer immunotherapy approach that helped two men in a 2010 clinical trial experience over 10 years of remission from their leukemia.ĭiagram of CAR T-cell therapy. Research tools at the time of implementation may not be advanced enough, lacking the needed resolution to understand the cellular and molecular basis of drug efficacy. Available technology can also be a limiting factor. More robust trials and, with that, time, are generally needed to build up mechanistic understanding too. ![]() As Pasteur was quoted, “Fortune favors the prepared mind” (1). Why might this be the case? For one, present needs of patients can drive innovative decisions in real time. ![]() Some of the most recognizable drugs-acetaminophen for pain relief, penicillin for infections, and lithium for bipolar disorder, continue to be scientific mysteries today” (1). “Knowing why a drug works has historically trailed the treatment, sometimes by decades. Deep understanding of drug mechanisms of action can, surprisingly often, follow treatment success. ![]() Detailed scientific understanding of how a drug works often comes, ironically enough, near the end of the process” (1).Īs this quote demonstrates, despite popular perception, scientists and doctors don’t always know exactly how drugs work to alleviate the complex symptoms of the diseases they treat. “Here’s how we actually develop a surprising number of treatments: good old-fashioned observation, trial and error, and luck. Drug mechanisms: When understanding trails treatment Using single cell immune profiling technology from 10x Genomics, the authors behind the original clinical study have investigated how the CAR T cells have evolved over the past decade to provide continuous protection from the return of cancer-amazing results that represent a potential step towards finding a cure. The secret to long-term treatment success has been a mystery, until now. In 2010, two patients received CAR T-cell therapy for advanced chronic lymphocytic leukemia, experiencing total remission in mere months. ![]()
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