B-cell maturation antigen (BCMA) in multiple myeloma: rationale for targeting and current therapeutic approaches.

Despite considerable advances in the treatment of multiple myeloma (MM) in the last decade, a substantial proportion of patients do not respond to current therapies or have a short duration of response. Furthermore, these treatments can have notable morbidity and are not uniformly tolerated in all patients. As there is no cure for MM, patients eventually become resistant to therapies, leading to development of relapsed/refractory MM. Therefore, an unmet need exists for MM treatments with novel mechanisms of action that can provide durable responses, evade resistance to prior therapies, and/or are better tolerated. B-cell maturation antigen (BCMA) is preferentially expressed by mature B lymphocytes, and its overexpression and activation are associated with MM in preclinical models and humans, supporting its potential utility as a therapeutic target for MM. Moreover, the use of BCMA as a biomarker for MM is supported by its prognostic value, correlation with clinical status, and its ability to be used in traditionally difficult-to-monitor patient populations. Here, we review three common treatment modalities used to target BCMA in the treatment of MM: bispecific antibody constructs, antibody-drug conjugates, and chimeric antigen receptor (CAR)-modified T-cell therapy. We provide an overview of preliminary clinical data from trials using these therapies, including the BiTE® (bispecific T-cell engager) immuno-oncology therapy AMG 420, the antibody-drug conjugate GSK2857916, and several CAR T-cell therapeutic agents including bb2121, NIH CAR-BCMA, and LCAR-B38M. Notable antimyeloma activity and high minimal residual disease negativity rates have been observed with several of these treatments. These clinical data outline the potential for BCMA-targeted therapies to improve the treatment landscape for MM. Importantly, clinical results to date suggest that these therapies may hold promise for deep and durable responses and support further investigation in earlier lines of treatment, including newly diagnosed MM

Ultraviolet Cancellations in Half-Maximal Supergravity as a Consequence of the Double-Copy Structure

We show that the double-copy structure of gravity forbids divergences in pure half-maximal (16 supercharge) supergravity at four and five points at one loop in D<8 and at two loops in D<6. We link the cancellations that render these supergravity amplitudes finite to corresponding ones that eliminate forbidden color factors from the divergences of pure nonsupersymmetric Yang-Mills theory. The vanishing of the two-loop four-point divergence in D=5 half-maximal supergravity is an example where a valid counterterm satisfying the known symmetries exists, yet is not present. We also give explicit forms of divergences in half-maximal supergravity at one loop in D=8 and at two loops in D=6.Comment: 32 pages, revtex, 6 figures, v3 minor correction

Twenty Years of Searching for (and Finding) Globular Cluster Pulsars

Globular clusters produce orders of magnitude more millisecond pulsars per unit mass than the Galactic disk. Since the first cluster pulsar was uncovered twenty years ago, at least 138 have been identified - most of which are binary millisecond pulsars. Because of their origins involving stellar encounters, many of these systems are exotic objects that would never be observed in the Galactic disk. Examples include pulsar-main sequence binaries, extremely rapid rotators (including the current record holder), and millisecond pulsars in highly eccentric orbits. These systems are allowing new probes of the interstellar medium, the equation of state of material at supra-nuclear density, the mass distribution of neutron stars, and the dynamics of globular clusters.Comment: 9 pages, 6 figures. Submitted review for the "40 Years of Pulsars" conference in Montreal, Aug 2007. To be published by the AI

Topical antihistamines and mast cell stabilisers for treating seasonal and perennial allergic conjunctivitis

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