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Supplementary information on cell maintenance, and antibody selection and characterization

FAP-drozitumab antibody-mediated apoptosis does not correlate with DR5.

Characterization and optimization of RG7386 dosing in vivo.

Dysregulated cellular apoptosis and resistance to cell death are hallmarks of neoplastic initiation and disease progression. Therefore, the development of agents that overcome apoptosis dysregulation in tumor cells is an attractive therapeutic approach. Activation of the extrinsic apoptotic pathway is strongly dependent on death receptor (DR) hyperclustering on the cell surface. However, strategies to activate DR5 or DR4 through agonistic antibodies have had only limited clinical success. To pursue an alternative approach for tumor-targeted induction of apoptosis, we engineered a bispecific antibody (BsAb), which simultaneously targets fibroblast-activation protein (FAP) on cancer-associated fibroblasts in tumor stroma and DR5 on tumor cells. We hypothesized that bivalent binding to both FAP and DR5 leads to avidity-driven hyperclustering of DR5 and subsequently strong induction of apoptosis in tumor cells but not in normal cells. Here, we show that RG7386, an optimized FAP-DR5 BsAb, triggers potent tumor cell apoptosis in vitro and in vivo in preclinical tumor models with FAP-positive stroma. RG7386 antitumor efficacy was strictly FAP dependent, was independent of FcR cross-linking, and was superior to conventional DR5 antibodies. In combination with irinotecan or doxorubicin, FAP-DR5 treatment resulted in substantial tumor regression in patient-derived xenograft models. FAP-DR5 also demonstrated single-agent activity against FAP-expressing malignant cells, due to cross-binding of FAP and DR5 across tumor cells. Taken together, these data demonstrate that RG7386, a novel and potent antitumor agent in both mono- and combination therapies, overcomes limitations of previous DR5 antibodies and represents a promising approach to conquer tumor-associated resistance to apoptosis. Mol Cancer Ther; 15(5); 946–57. ©2016 AACR.

Figure S2. Related to Figure 3. In vitro characterization of the FAP-DR5 BsAb RG7386; Table S4. Characterization of RG7386 binding avidities.

Figure S1. Related to Figure 1. Characterization of FAP-drozitumab BsAbs and antitumor efficacy in the presence of FAP-expressing fibroblasts in in vitro co-culture models; Table S1. BsAb binding to DR5 and FAP antigens; Table S2. Anti-tumor efficacy of FAP-drozitumab bispecific molecules is FAPdependent.

In this paper, an advanced duplex scheme called cross-division duplex (XDD) is proposed to enhance uplink (UL) coverage in time division duplex (TDD) carriers by utilizing self-interference cancellation (SIC) capability at a base station. With XDD, it is possible to combine TDD’s ability to efficiently handle asymmetric UL and downlink (DL) traffic with frequency division duplex’s coverage advantage. To do so, XDD simultaneously operates UL and DL on the same TDD carrier but on different frequency resources. Such operation leads to severe interference on the received UL signal at the base station which requires two levels of SIC implementation; antenna and digital SIC. More than 50 dB of interference is removed through the antenna SIC using electromagnetic barriers between the transmitting and receiving antennas. The remaining interference is removed by the digital SIC based on estimating the non-linear channel of the circuit at the receiver baseband. It is verified by simulation and analysis that with the proposed XDD, the UL coverage can be improved by up to 2.37 times that of TDD. To check the feasibility of XDD, a Proof-of-Concept was developed where it was observed that the benefits of XDD can indeed be realized using the proposed SIC techniques.

This paper investigates the capability of millimeter-wave (mmWave) channel sounders with phased arrays to perform super-resolution parameter estimation, i.e., determine the parameters of multipath components (MPC), such as direction of arrival and delay, with resolution better than the Fourier resolution of the setup. We analyze the question both generally, and with respect to a particular novel multi-beam mmWave channel sounder that is capable of performing multiple-input-multiple-output (MIMO) measurements in dynamic environments. We firstly propose a novel two-step calibration procedure that provides higher-accuracy calibration data that are required for Rimax or SAGE. Secondly, we investigate the impact of center misalignment and residual phase noise on the performance of the parameter estimator. Finally we experimentally verify the calibration results and demonstrate the capability of our sounder to perform super-resolution parameter estimation.

THz band communication has the potential to meet the high data rate demands of many current and future applications. However, before these networks are realized, extensive channel measurements are needed in order to characterize the wireless channel at these frequencies, in order to inform system design and deployment. In the current paper, we present a set of double-directional channel measurements that are conducted in several relevant indoor and outdoor scenarios. Our aim is to see the effect of common building materials that might be particularly reflective or absorptive (such as energy-saving glass, window blinds, or metallic reflectors), and how their presence changes the channel characteristics. Among other effects we find that - depending on the considered dynamic range - presence/absence of these materials can increase the required equalizer length by an order of magnitude.

It is projected that mobile traffic will increase by 80x by year 2030. To meet this increase in demand, it is inevitable to utilize the terahertz bands (0.1 THz to 10 THz) for future 6G wireless systems. However, operating at such high frequency comes with several fundamental and technical challenges. In this work, we present a proof-of-concept system to demonstrate the feasibility of establishing a communication link at 140 GHz carrier frequency. In addition, this work highlights techniques to tackle the challenges that comes with operating in the terahertz regime. To the authors knowledge, this is the world’s first end-to-end system with up to 16-channel digitally-beamformed 140 GHz system and dynamic beam steering capability. The paper presents lab results which demonstrate link throughput of 6 Gbps at 15-meter distance with adaptive beamforming.

In this paper, an advanced duplex (AD) scheme is proposed to use flexible downlink (DL) and uplink (UL) allocation in time division duplex (TDD) carrier in 6G. By utilizing self-interference cancellation (SIC) capability at a base station to handle the interference from DL signal to UL signal, the proposed duplex scheme enables to simultaneously operate UL and DL on the same carrier but on different frequency resources. To do so, both TDD’s ability to efficiently handle asymmetric UL and DL traffic and frequency division duplexing’s coverage advantage can be achieved together in the AD scheme. To verify the feasibility, a Proof-of-Concept is developed where it is observed that the benefits of AD scheme can indeed be realized using the proposed SIC techniques. In a system having a 100 MHz bandwidth in the 2.4 GHz band, a multi-level SIC is applied to suppress the self-interference to less than 1 dB without a guard band between DL and UL signals. Based on this technology, in 6G, various duplex techniques can be applied in a time-varying manner, so that a significantly higher resource utilization than the existing 5G will be possible.

Wireless communications in the THz frequency range can allow data rates of hundreds of Gbit/s, and will thus be an important part of 6G. A first important step for system design is an understanding of the underlying propagation channel. In this paper, we present results from one of the first measurement campaigns for medium-distance (up to 35 m) outdoor channels in urban environments where both the directions and delays of multipath are measured with good resolution. The results show a surprisingly rich multipath environment, leading to significant dispersion in both delay and angular domains. We also find that metallic-covered surfaces lead to a considerable enhancement of multipath, which indicates an important impact of building materials. Overall, the results indicate that relying on pronounced sparsity for THz system design might not always be valid in this type of environment.

The large swaths of bandwidth available in the THz band (0.1-10 THz) make it an ideal candidate to meet the ever-increasing data rate demands for upcoming applications. However, detailed channel sounding measurements are required before an eventual deployment of THz band communication can be considered. Keeping this goal in mind, in the current paper we present double-directional channel measurements in the 140-141 GHz range in an urban environment on a linear route for distances up to 15 m. Using our results, we analyze how key channel parameters change as we move from short to longer distances. These measurements allow us to take another step towards creation of detailed THz channel models.

Current trends in the evolution of mobile communication systems address the data throughput demand by expanding to higher frequency bands as the usable spectrum in lower frequency bands is almost depleted. As the Third Generation Partnership Project (3GPP) specified the support of mmWave band operations for 5G New Radio (NR), it is expected that the next generation mobile communication system, namely 6G, will consider even higher terahertz (THz) spectrum with wider bandwidth to continue supporting exponential growth of data rates. However, the question remains how to deal with various technical challenges stemming from harsh THz radio propagation characteristics as well as the feasibility of radio frequency (RF) components, which we try to answer in this work. To this end, it is our goal to demonstrate the promise of THz spectrum for the next generation communication systems.