Antibody-Based Immunotherapy of Cancer

By targeting surface antigens expressed on tumor cells, monoclonal antibodies have demonstrated efficacy as cancer therapeutics. Recent successful antibody-based strategies have focused on enhancing antitumor immune responses by targeting immune cells, irrespective of tumor antigens. We discuss these innovative strategies and propose how they will impact the future of antibody-based cancer therapy

Type Ia Supernova Rate Measurements To Redshift 2.5 From CANDELS: Searching For Prompt Explosions In The Early Universe

dThe Cosmic Assembly Near-infrared Deep Extragalactic Legacy Survey (CANDELS) was a multi-cycle treasury program on the Hubble Space Telescope (HST) that surveyed a total area of -0.25 deg2 with -900 HST orbits spread across five fields over three years. Within these survey images we discovered 65 supernovae (SNe) of all types, out to z 2.5. We classify -24 of these as Type Ia SNe (SNe Ia) based on host galaxy redshifts and SN photometry (supplemented by grism spectroscopy of six SNe). Here we present a measurement of the volumetric SN Ia rate as a function of redshift, reaching for the first time beyond z =- 2 and putting new constraints on SN Ia progenitor models. Our highest redshift bin includes detections of SNe that exploded when the universe was only -3 Gyr old and near the peak of the cosmic star formation history. This gives the CANDELS high redshift sample unique leverage for evaluating the fraction of SNe Ia that explode promptly after formation ( 40 Myr. However, mild tension is apparent between ground-based low-z surveys and space-based high-z surveys. In both CANDELS and the sister HST program CLASH (Cluster Lensing And Supernova Survey with Hubble), we find a low rate of SNe Ia at z > 1. This could be a hint that prompt progenitors are in fact relatively rare, accounting for only 20% of all SN Ia explosions-though further analysis and larger samples will be needed to examine that suggestion. Key words: infrared: general - supernovae:Astronom

BMQ

BMQ: Boston Medical Quarterly was published from 1950-1966 by the Boston University School of Medicine and the Massachusetts Memorial Hospitals

Genome-wide multi-omics profiling of colorectal cancer identifies immune determinants strongly associated with relapse

The use and benefit of adjuvant chemotherapy to treat stage II colorectal cancer (CRC) patients is not well understood since the majority of these patients are cured by surgery alone. Identification of biological markers of relapse is a critical challenge to effectively target treatments to the ~20% of patients destined to relapse. We have integrated molecular profiling results of several “omics” data types to determine the most reliable prognostic biomarkers for relapse in CRC using data from 40 stage I and II CRC patients. We identified 31 multi-omics features that highly correlate with relapse. The data types were integrated using multi-step analytical approach with consecutive elimination of redundant molecular features. For each data type a systems biology analysis was performed to identify pathways biological processes and disease categories most affected in relapse. The biomarkers detected in tumors urine and blood of patients indicated a strong association with immune processes including aberrant regulation of T-cell and B-cell activation that could lead to overall differences in lymphocyte recruitment for tumor infiltration and markers indicating likelihood of future relapse. The immune response was the biologically most coherent signature that emerged from our analyses among several other biological processes and corroborates other studies showing a strong immune response in patients less likely to relapse

Adrenergic β2 receptor activation stimulates anti-inflammatory properties of dendritic cells in vitro

Vagal nerve efferent activation has been shown to ameliorate the course of many inflammatory disease states. This neuromodulatory effect has been suggested to rest on acetylcholine receptor (AChR) activation on tissue macrophages or dendritic cells (DCs). In more recent studies, vagal anti-inflammatory activity was shown involve adrenergic, splenic, pathways. Here we provide evidence that the adrenergic, rather than cholinergic, receptor activation on bone marrow derived DCs results in enhanced endocytosis uptake, enhanced IL-10 production but a decreased IL-6, IL-12p70 and IL-23 production. In antigen specific T cell stimulation assays, adrenergic β2 receptor activation on bone marrow DCs led to an enhanced potential to induce Foxp3 positive suppressive Treg cells. These effects were independent of IL10-R activation, TGFβ release, or retinoic acid (RA) secretion. Hence, adrenergic receptor β2 activation modulates DC function resulting in skewing towards anti-inflammatory T cell phenotypes

Consensus Statement: Expedition Inspiration Fund for Breast Cancer Research Meeting 2002

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44212/1/10549_2004_Article_5094133.pd