After unprecedented successes in B-cell malignancies, chimeric antigen receptor T cells have recently been investigated for the treatment of multiple myeloma. Chimeric antigen receptor targeting T cells B-cell maturation antigen (BCMA) on malignant plasma cells have led to impressive clinical responses in recent trials. However, BCMA-negative relapses have been observed, supporting the need for complementary treatment strategies. Here, we explored the feasibility of targeting CD138 (syndecan-1), a surface marker expressed on both normal and malignant plasma cells. We showed that T cells from both healthy donors and from multiple myeloma patients, when transduced with a CD138-specific chimeric antigen receptor, can eliminate tumor cell lines and primary myeloma cells both in vitro and in vivo. CD138 is also expressed by putative myeloma stem cells identified by Hoechst staining, and these cells can be eliminated by CD138-specific chimeric antigen receptor T cells. Preclinical analyses did not identify any on target off tumor cytotoxicity against normal epithelial or endothelial cells, further supporting the rationale for the use of adoptively transferred CD138-specific chimeric antigen receptor T cells for the treatment of patients with relapsed/refractory multiple myeloma.

TPS3095 Background: CAR-T therapy has emerged as one of the most promising therapeutic approaches for lymphoma. CD30 antigen is expressed on virtually all Hodgkin (HL) and various subtypes of non-Hodgkin lymphoma (NHL). HL and NHL are both sensitive to the cellular immune response and antibody-directed therapy, which makes CD30 an excellent target for CAR-Ts. In the “first-in-human” clinical trial of CD30.CAR-Ts, the dose of 2 × 108 CD30.CAR-Ts/m2 was found to be safe; however, no conditioning therapy was given prior to CD30.CAR-T infusion and the expansion of CAR-Ts was thus limited. In the current study, we have further developed the CD30.CAR-T-based therapy by combining it with bendamustine. We hypothesized that bendamustine may improve therapeutic efficacy of CD30.CAR-Ts by causing sufficient depletion of endogenous immune cells to facilitate the expansion and persistence of CAR-Ts in vivo. Methods: In this phase 1b/2 clinical study, patients with CD30+ HL or NHL receive bendamustine followed by CD30.CAR-Ts (NCT02690545). The primary objective is to establish the safety of CD30.CAR-Ts in combination with bendamustine. Secondary objectives include estimation of 2-year overall and progression-free survival rates. Patients receive bendamustine (90 mg/m2 on days 1 and 2) followed by CD30.CAR-Ts within 1 to 4 days of lymphodepletion. The maximal tolerated dose is determined based on 3 + 3 design for dose escalation starting at 1 × 108 CD30.CAR-Ts/m2. If the first 3 enrolled subjects do not experience a DLT within 6 weeks of the cell infusion, the number of cells for the infusion is increased to 2 x 108/m2. Once the number of cells for infusion is established, up to 25 subjects will be enrolled in the Phase 2 portion of the study to further establish the safety and efficacy of this treatment regimen. Response will be assessed at 6 weeks after CD30.CAR-Ts infusion, and a second CD30.CAR-Ts infusion equal to or lower than the dose may be administered to patients with partial response or stable disease. Patient’s peripheral blood samples will be evaluated at various time points to monitor safety, function, and persistence of transduced T-cells. Clinical trial information: NCT02690545.

The ability to electrically control the optical properties of metamaterials is an essential capability required for technological innovation. The creation of dynamic electrically tunable metamaterials in the visible and near infrared regions is important for a range of imaging and fiber optic technologies. However, current approaches require complex nanofabrication processes which are incompatible for low‐cost device production. Herein, a novel simple approach is reported for electrical control of optical properties which uses a flexoelectric dielectric element to electromechanically manipulate the form factor of a chiral nanostructure. By altering the dimensions of the chiral nanostructure, the polarization properties of light are allowed to be electrically controlled. The flexoelectric element is part of a composite metafilm that is templated onto a nanostructured polymer substrate. As the flexoelectric element does not require in situ high temperature annealing, it can be readily combined with polymer‐based substrates produced by high throughput methods. This is not the case for piezoelectric elements, routinely used in microelectromechanical (MEM) devices which require high temperature processing. Consequently, combining amorphous flexoelectric dielectrics and low‐cost polymer‐based materials provides a route to the high throughput production of electrically responsive disposable metadevices.

Manipulating symmetry environments of metal ions to control functional properties is a fundamental concept of chemistry. For example, lattice strain enables control of symmetry in solids through a change in the nuclear positions surrounding a metal centre. Light–matter interactions can also induce strain but providing dynamic symmetry control is restricted to specific materials under intense laser illumination. Here, we show how effective chemical symmetry can be tuned by creating a symmetry-breaking rotational bulk polarisation in the electronic charge distribution surrounding a metal centre, which we term a meta-crystal field. The effect arises from an interface-mediated transfer of optical spin from a chiral light beam to produce an electronic torque that replicates the effect of strain created by high pressures. Since the phenomenon does not rely on a physical rearrangement of nuclear positions, material constraints are lifted, thus providing a generic and fully reversible method of manipulating effective symmetry in solids.

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