Chimeric antigen receptor (CAR) T cells targeting the CD19 antigen are effective in treating adults and children with B-cell malignancies. Place-of-care manufacturing may improve performance and ...accessibility by obviating the need to cryopreserve and transport cells to centralized facilities. Here we develop an anti-CD19 CAR (CAR19) comprised of the 4-1BB co-stimulatory and TNFRSF19 transmembrane domains, showing anti-tumor efficacy in an in vivo xenograft lymphoma model. CAR19 T cells are manufactured under current good manufacturing practices (cGMP) at two disparate clinical sites, Moscow (Russia) and Cleveland (USA). The CAR19 T-cells is used to treat patients with relapsed/refractory pediatric B-cell Acute Lymphocytic Leukemia (ALL; n = 31) or adult B-cell Lymphoma (NHL; n = 23) in two independently conducted phase I clinical trials with safety as the primary outcome (NCT03467256 and NCT03434769, respectively). Probability of measurable residual disease-negative remission was also a primary outcome in the ALL study. Secondary outcomes include complete remission (CR) rates, overall survival and median duration of response. CR rates are 89% (ALL) and 73% (NHL). After a median follow-up of 17 months, one-year survival rate of ALL complete responders is 79.2% (95%CI 64.5‒97.2%) and median duration of response is 10.2 months. For NHL complete responders one-year survival is 92.9%, and median duration of response has not been reached. Place-of-care manufacturing produces consistent CAR-T cell products at multiple sites that are effective for the treatment of patients with B-cell malignancies.
Search for C-optimal routes in graphs Bugaev, Yu. V.; Chikunov, S. V.; Muzalevskii, F. A.
Automation and remote control,
11/2017, Letnik:
78, Številka:
11
Journal Article
Recenzirano
We propose search algorithms for paths in graphs that are optimal in the sense of a given choice function. As an example we consider the choice mechanism with respect to a binary relation that does ...not contain numerical criterial estimates.
Mass measurements of the \(^{69}\)As, \(^{70,71}\)Se and \(^{71}\)Br isotopes, produced via fragmentation of a \(^{124}\)Xe primary beam at the FRS at GSI, have been performed with the ...multiple-reflection time-of-flight mass spectrometer (MR-TOF-MS) of the FRS Ion Catcher with an unprecedented mass resolving power of almost 1,000,000. For the \(^{69}\)As isotope, this is the first direct mass measurement. A mass uncertainty of 22 keV was achieved with only 10 events. For the \(^{70}\)Se isotope, a mass uncertainty of 2.6 keV was obtained, corresponding to a relative accuracy of \(\delta\)m/m = 4.0\(\times 10^{-8}\), with less than 500 events. The masses of the \(^{71}\)Se and \(^{71}\)Br isotopes were measured with an uncertainty of 23 and 16 keV, respectively. Our results for the \(^{70,71}\)Se and \(^{71}\)Br isotopes agree with the 2016 Atomic Mass Evaluation, and our result for the \(^{69}\)As isotope resolves the discrepancy between previous indirect measurements. We measured also the mass of \(^{14}\)N\(^{15}\)N\(^{40}\)Ar (A=69) with a relative accuracy of \(\delta\)m/m = 1.7\(\times 10^{-8}\), the highest yet achieved with a MR-TOF-MS. Our results show that the measured restrengthening of the proton-neutron interaction (\(\delta\)V\(_{pn}\)) for odd-odd nuclei at the N=Z line above Z=29 (recently extended to Z=37) is hardly evident at N-Z=2, and not evident at N-Z=4. Nevertheless, detailed structure of \(\delta\)V\(_{pn}\) along the N-Z=2 and N-Z=4 lines, confirmed by our mass measurements, may provide a hint regarding the ongoing \(\approx\)500 keV discrepancy in the mass value of the \(^{70}\)Br isotope, which prevents including it in the world average of \({Ft}\)-value for superallowed 0\(^+\rightarrow\) 0\(^+\) \(\beta\) decays. The reported work sets the stage for mass measurements with the FRS Ion Catcher of nuclei at and beyond the N=Z line in the same region of the nuclear chart, including the \(^{70}\)Br isotope.
PDF
