0000000000162619
AUTHOR
Andreas Wolf
Tumor Regression in Cancer Patients by Very Low Doses of a T Cell–Engaging Antibody
Previous attempts have shown the potential of T cells in immunotherapy of cancer. Here, we report on the clinical activity of a bispecific antibody construct called blinatumomab, which has the potential to engage all cytotoxic T cells in patients for lysis of cancer cells. Doses as low as 0.005 milligrams per square meter per day in non–Hodgkin's lymphoma patients led to an elimination of target cells in blood. Partial and complete tumor regressions were first observed at a dose level of 0.015 milligrams, and all seven patients treated at a dose level of 0.06 milligrams experienced a tumor regression. Blinatumomab also led to clearance of tumor cells from bone marrow and liver. T cell–engag…
Test of Time Dilation Using StoredLi+Ions as Clocks at Relativistic Speed
We present the concluding result from an Ives-Stilwell-type time dilation experiment using 7Li+ ions confined at a velocity of β=v/c=0.338 in the storage ring ESR at Darmstadt. A Λ-type three-level system within the hyperfine structure of the 7Li+3S1 →3P2 line is driven by two laser beams aligned parallel and antiparallel relative to the ion beam. The lasers' Doppler shifted frequencies required for resonance are measured with an accuracy of <4×10(-9) using optical-optical double resonance spectroscopy. This allows us to verify the special relativity relation between the time dilation factor γ and the velocity β, γ√1-β2=1 to within ±2.3×10(-9) at this velocity. The result, which is singled …
Test of Time Dilation Using Stored Li+ Ions as Clocks at Relativistic Speed
We present the concluding result from an Ives-Stilwell-type time dilation experiment using 7Li+ ions confined at a velocity of β=v/c=0.338 in the storage ring ESR at Darmstadt. A Λ-type three-level system within the hyperfine structure of the 7Li+3S1 → 3P2 line is driven by two laser beams aligned parallel and antiparallel relative to the ion beam. The lasers’ Doppler shifted frequencies required for resonance are measured with an accuracy of 2=1 to within ±2.3×10−9 at this velocity. The result, which is singled out by a high boost velocity β, is also interpreted within Lorentz invariance violating test theories.
Test of relativistic time dilation with fast optical atomic clocks at different velocities
Time dilation is one of the most fascinating aspects of special relativity as it abolishes the notion of absolute time. It was first observed experimentally by Ives and Stilwell in 1938 using the Doppler effect. Here we report on a method, based on fast optical atomic clocks with large, but different Lorentz boosts, that tests relativistic time dilation with unprecedented precision. The approach combines ion storage and cooling with optical frequency counting using a frequency comb. 7Li+ ions are prepared at 6.4% and 3.0% of the speed of light in a storage ring, and their time is read with an accuracy of 2×10−10 using laser saturation spectroscopy. The comparison of the Doppler shifts yield…
Polarization-Dependent Disappearance of a Resonance Signal -- Indication for Optical Pumping in a Storage Ring?
We report on laser spectroscopic measurements on Li$^+$ ions in the experimental storage ring ESR at the GSI Helmholtz Centre for Heavy Ion Research. Driving the $2s\,^3\!{S}_1\;(F=\frac{3}{2}) \,\leftrightarrow\,2p\,^3\!P_2\;(F=\frac{5}{2}) \leftrightarrow 2s\,^3\!{S}_1\;(F=\frac{5}{2})$ $\Lambda$-transition in $^7$Li$^+$ with two superimposed laser beams it was found that the use of circularly polarized light leads to a disappearance of the resonance structure in the fluorescence signal. This can be explained by optical pumping into a dark state of polarized ions. We present a detailed theoretical analysis of this process that supports the interpretation of optical pumping and demonstrate…
Bispecific T-Cell Engager (BiTE) Antibody Construct Blinatumomab for the Treatment of Patients With Relapsed/Refractory Non-Hodgkin Lymphoma : Final Results From a Phase I Study
Purpose Blinatumomab is a CD19/CD3 BiTE (bispecific T-cell engager) antibody construct for the treatment of Philadelphia chromosome–negative acute B-lymphoblastic leukemia. We evaluated blinatumomab in relapsed/refractory B-cell non-Hodgkin lymphoma (NHL). Patients and Methods This 3 + 3 design, phase I dose-escalation study determined adverse events and the maximum tolerated dose (MTD) of continuous intravenous infusion blinatumomab in patients with relapsed/refractory NHL. Blinatumomab was administered over 4 or 8 weeks at seven different dose levels (0.5 to 90 μg/m2/day). End points were incidence of adverse events, pharmacokinetics, pharmacodynamics, and overall response rate. Results B…
First laser cooling of relativistic ions in a storage ring
The first successful laser cooling of ions at relativistic energies was observed at the Heidelberg TSR storage ring. A $^{7}\mathrm{Li}^{+}$-ion beam of 13.3 MeV was oberlapped with resonant copropagating and counterpropagating laser beams. The metastable ions were cooled from 260 K to a longitudinal temperature of below 3 K and decelerated by several keV. The longitudinal velocity distribution was determined by a fluorescence method. After laser cooling a strongly enhanced narrow peak appeared in the Schottky noise spectrum in addition to the uncooled ion distribution.
First experiments with the heidelberg test storage ring TSR
Abstract The Heidelberg heavy ion test storage ring TSR started operation in May 1988. The lifetimes of the ion beams observed in the first experiments can be explained by interactions with the residual gas. Multiple Coulomb scattering, single Coulomb scattering, electron capture and electron stripping are the relevant processes. Electron cooling of ions as heavy as O 8+ has been observed for the first time. With increasing particle number, the longitudinal Schottky noise spectrum becomes dominated by collective waves for cooled beams, allowing a determination of velocities of sound. After correcting for these coherent distortions fo the Schottky spectrum, the longitudinal beam temperature …