AD: Shocked! The peak value of plasma Aβ42/Aβ40 began to decline 41 years before the deposition of brain Aβ! Alzheimer's diseases: New discovery on plasma Aβ42/Aβ40. AD: Shocked! The peak value of plasma Aβ42/Aβ40 began to decline 41 years before the deposition of brain Aβ! Amyloid β (Aβ) plaque deposition and phosphorylated tau (p-tau) protein tangles are two important pathological features of Alzheimer's disease (AD), and there are many kinds of AD biomarkers derived around them, Knowledge of the longitudinal trajectories of key markers could not only help improve the selection and monitoring of participants in clinical trials, but also help identify those at high risk for neurodegenerative changes and cognitive impairment. Although research on AD biomarkers has increased substantially in recent years, research on longitudinal changes in biomarkers is relatively limited. Studies have shown that the levels of plasma Aβ 42 /Aβ 40 , p-tau181 and glial fibrillary acidic...
Bispecific CD19/CD20 CAR-T cell therapy: treatment of relapsed or refractory B-cell lymphoma with a complete remission rate of 80%!
Bispecific CD19/CD20 CAR-T cell therapy: treatment of relapsed or refractory B-cell lymphoma with a complete remission rate of 80%!
-According to the data of a phase I clinical trial (NCT04007029) announced in the first week of the American Association for Cancer Research (AACR) 2021 annual meeting, bispecific anti-CD19/CD20 CAR-T cell therapy treats relapsed/refractory B Patients with cell lymphoma are well tolerated and show clinical efficacy.
Researcher Sanaz Ghafouri, MD, a researcher in hematology and oncology at the University of California, Los Angeles Medical Center, said: “Patients with relapsed/refractory B-cell lymphoma often have more malignant disease trajectories and limited treatment options. Anti-CD19 CAR- T cell therapy has completely changed the treatment of this disease in recent years, but there are still some limitations. Due to the lack of persistence of CAR-T cells and/or the down-regulation of the target antigen CD19 on the tumor, about half of the patients are within 6 months of starting treatment Relapse. Therefore, patients who relapse after receiving CAR-T cell therapy have a very poor prognosis."
Bispecific CAR-T cells simultaneously target two tumor antigens and have been explored as a strategy to reduce the risk of recurrence. In this study, Sanaz Ghafouri and his colleagues used primitive memory cells to evaluate the safety and effectiveness of anti-CD19/CD20 bispecific CAR-T cells.
Sanaz Ghafouri said: "This is the first bispecific CAR-T cell therapy developed and tested on patients using primitive memory T cells. We hypothesize that this method may increase the persistence and persistence of CAR-T cells in patients. Expansibility, while limiting the recurrence caused by the loss of tumor antigens."
The conference report analyzed 5 CD19 and CD20 tumor antigen-positive B-cell malignancies. The median number of treatment options previously received by these patients was 4, and 4 patients received bridging therapy. Original memory T cells were extracted from each patient, designed to express anti-CD19/CD20 CAR, expanded, and used in 2 different doses (5×10 7th power cells or 2×10 8th power cells ) Is injected into the patient's body.
After a median follow-up of 13 months, 4 out of 5 patients had sustained complete remission (CR). Patients who fail to treat the disease develop early disease progression on the 14th day after the infusion and are CD19/CD20 negative. At follow-up, the median progression-free survival (PFS) and overall survival (OS) were not reached, and all patients with remission still had CAR-T cells persisting at the time of data cutoff.
No dose-limiting toxicity or immune effector cell-related neurotoxicity was observed in all patients. All patients developed grade 1 cytokine release syndrome (CRS), and all patients who responded to treatment had persistent B-cell aplasia at the time of data cut-off.
Sanaz Ghafouri said: "Despite the need for long-term follow-up and analysis of additional patients, our results show that in patients with relapsed or refractory B-cell lymphoma, the use of bispecific anti-CD19/CD20 in primitive memory T cells CAR may be safe and effective. Our findings increase the possibility of bispecific CAR-T cell therapy for patients with this aggressive disease to achieve long-term remission."
Sanaz Ghafouri and his colleagues plan to expand their patient cohort and are interested in evaluating treatments for other subtypes of B-cell lymphoma. Limitations of the study include small sample size and lack of long-term follow-up. The research was supported by the Parker Institute of Cancer Immunotherapy and donations from Stephen and Joan Kaplan. Sanaz Ghafouri stated that there is no conflict of interest.