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 cancerassociated 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 crosslinking, 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.

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THz band is envisioned to be used in 6G systems to meet the ever-increasing demand for data rate.However, before an eventual system design and deployment can proceed, detailed channel sounding measurements are required to understand key channel characteristics. In this paper, we present a first extensive set of channel measurements for urban outdoor environments that are ultra-wideband (1 GHz 3dB bandwidth), and double-directional where both the transmitter and receiver are at the same height.In all, we present measurements at 38 Tx/Rx location pairs, consisting of a total of nearly 50,000 impulse responses, at both line-of-sight (LoS) and non-line-of-sight (NLoS) cases in the 1-100 m range.We provide modeling for path loss, shadowing, delay spread, angular spread and multipath component (MPC) power distribution. We find, among other things, that outdoor communication over tens of meters is feasible in this frequency range even in NLoS scenarios, that omni-directional delay spreads of up to 100 ns, and directional delay spreads of up to 10 ns are observed, while angular spreads are also quite significant, and a surprisingly large number of MPCs are observed for 1 GHz bandwidth and 13 • beamwidth. These results constitute an important first step towards better understanding the wireless channel in the THz band.

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