A Therapeutic Antibody for Cancer, Derived from Single Human B Cells.

Some patients with cancer never develop metastasis, and their host response might provide cues for innovative treatment strategies. We previously reported an association between autoantibodies against complement factor H (CFH) and early-stage lung cancer. CFH prevents complement-mediated cytotoxicity (CDC) by inhibiting formation of cell-lytic membrane attack complexes on self-surfaces. In an effort to translate these findings into a biologic therapy for cancer, we isolated and expressed DNA sequences encoding high-affinity human CFH antibodies directly from single, sorted B cells obtained from patients with the antibody. The co-crystal structure of a CFH antibody-target complex shows a conformational change in the target relative to the native structure. This recombinant CFH antibody causes complement activation and release of anaphylatoxins, promotes CDC of tumor cell lines, and inhibits tumor growth in vivo. The isolation of anti-tumor antibodies derived from single human B cells represents an alternative paradigm in antibody drug discovery.

A Binaural Cochlear Implant Sound Coding Strategy Inspired by the Contralateral Medial Olivocochlear Reflex.

OBJECTIVES: In natural hearing, cochlear mechanical compression is dynamically adjusted via the efferent medial olivocochlear reflex (MOCR). These adjustments probably help understanding speech in noisy environments and are not available to the users of current cochlear implants (CIs). The aims of the present study are to: (1) present a binaural CI sound processing strategy inspired by the control of cochlear compression provided by the contralateral MOCR in natural hearing; and (2) assess the benefits of the new strategy for understanding speech presented in competition with steady noise with a speech-like spectrum in various spatial configurations of the speech and noise sources. DESIGN: Pairs of CI sound processors (one per ear) were constructed to mimic or not mimic the effects of the contralateral MOCR on compression. For the nonmimicking condition (standard strategy or STD), the two processors in a pair functioned similarly to standard clinical processors (i.e., with fixed back-end compression and independently of each other). When configured to mimic the effects of the MOCR (MOC strategy), the two processors communicated with each other and the amount of back-end compression in a given frequency channel of each processor in the pair decreased/increased dynamically (so that output levels dropped/increased) with increases/decreases in the output energy from the corresponding frequency channel in the contralateral processor. Speech reception thresholds in speech-shaped noise were measured for 3 bilateral CI users and 2 single-sided deaf unilateral CI users. Thresholds were compared for the STD and MOC strategies in unilateral and bilateral listening conditions and for three spatial configurations of the speech and noise sources in simulated free-field conditions: speech and noise sources colocated in front of the listener, speech on the left ear with noise in front of the listener, and speech on the left ear with noise on the right ear. In both bilateral and unilateral listening, the electrical stimulus delivered to the test ear(s) was always calculated as if the listeners were wearing bilateral processors. RESULTS: In both unilateral and bilateral listening conditions, mean speech reception thresholds were comparable with the two strategies for colocated speech and noise sources, but were at least 2 dB lower (better) with the MOC than with the STD strategy for spatially separated speech and noise sources. In unilateral listening conditions, mean thresholds improved with increasing the spatial separation between the speech and noise sources regardless of the strategy but the improvement was significantly greater with the MOC strategy. In bilateral listening conditions, thresholds improved significantly with increasing the speech-noise spatial separation only with the MOC strategy. CONCLUSIONS: The MOC strategy (1) significantly improved the intelligibility of speech presented in competition with a spatially separated noise source, both in unilateral and bilateral listening conditions; (2) produced significant spatial release from masking in bilateral listening conditions, something that did not occur with fixed compression; and (3) enhanced spatial release from masking in unilateral listening conditions. The MOC strategy as implemented here, or a modified version of it, may be usefully applied in CIs and in hearing aids.