M-protein Binding Peptides from Phage Display Libraries as Biomarkers in Multiple Myeloma: a Paradigm for Early Detection of Disease Relapse

Abstract The presence of metaphase cytogenetic abnormalities (CA) has long been considered an adverse prognosticator in multiple myeloma (MM). An update is provided of overall survival (OS) and progression-free survival (PFS) of patients treated with Total Therapy 3 (TT3). The prognostic role of CA was assessed relative to its presence at baseline (BL) and during 2 landmarks (LM) of 2 (LM2) and 5 years of follow-up (LM5). For both LM, the following CA combinations were considered: no CA at BL and up to LM; CA at BL and till LM; CA at BL, no CA till LM; no CA at BL, CA toward LM. Patients considered for evaluation had at least one cytogenetic evaluation prior to the start of therapy and at least one cytogenetic evaluation during follow-up. In Cox modeling, only patients with at least one cytogenetic evaluation prior to baseline were considered. The time-dependent variable indicating whether patients lived to reach a certain LM, and had a CA during the time between enrollment and that LM, was considered along with several typical MM predictor variables. Results showed that, for the LM2, patients with BL-no CA/LM-no CA fared best followed by the BL-CA/LM-no CA combination, with worst outcomes seen in the remainder sharing LM-CA (Figure 1a). In case of the LM5, LM-no CA was superior regardless of BL-CA status, while LM-CA conferred equally poor OS regardless of BL-CA status (Figure 1b). On multivariate analysis, LM5-CA retained the highest HR along with GEP-70-defined high-risk MM, BL-CA and creatinine elevation. We conclude that serial CA monitoring provides a simple cost-effective tool contributing to early detection of disease relapse often without clinical progression (data not shown) that also affords the early detection of MDS-associated CA, an increasing complication of MM therapy. Data will be presented on the detection at BL of GEP features forecasting CA development during 2 and 5 years of follow up. Disclosures: Usmani: Celgene: Consultancy, Research Funding, Speakers Bureau; Onyx: Research Funding, Speakers Bureau.

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Early detection of IgH monoclonal rearrangement in follicular spicules of the nose preceding multiple myeloma diagnosis

Giornale Italiano di Dermatologia e Venereologia ◽

10.23736/s0392-0488.18.06016-9 ◽

2020 ◽

Vol 155 (3) ◽

Author(s):

Mauro Mazzeo ◽

Cosimo Di Raimondo ◽

Carmelo Gurnari ◽

Maria Cristina Rapanotti ◽

Alessandro Giunta ◽

...

Keyword(s):

Multiple Myeloma ◽

Early Detection

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Faculty Opinions recommendation of The use of mRNA display to select high-affinity protein-binding peptides.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1005033.59206 ◽

2002 ◽

Author(s):

Michael Yarus

Keyword(s):

Protein Binding ◽

Mrna Display ◽

High Affinity ◽

Binding Peptides

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Using SNSs for early detection of disease outbreak in developing countries: Evidence from COVID-19 pandemic in Nigeria

Heliyon ◽

10.1016/j.heliyon.2021.e07184 ◽

2021 ◽

pp. e07184

Author(s):

Tunde Adebisi ◽

Ayooluwa Aregbesola ◽

Festus Asamu ◽

Ogadimma Arisukwu ◽

Eyitayo Oyeyipo

Keyword(s):

Developing Countries ◽

Early Detection ◽

Disease Outbreak ◽

Early Detection Of Disease

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Screening of potent neutralizing antibodies against SARS-CoV-2 using convalescent patients-derived phage-display libraries

Cell Discovery ◽

10.1038/s41421-021-00295-w ◽

2021 ◽

Vol 7 (1) ◽

Author(s):

Yongbing Pan ◽

Jianhui Du ◽

Jia Liu ◽

Hai Wu ◽

Fang Gui ◽

...

Keyword(s):

Phage Display ◽

Neutralizing Antibodies ◽

Variable Region ◽

Neutralizing Antibody ◽

Chain Gene ◽

Prophylactic Efficacy ◽

Heavy Chains ◽

Effective Interventions ◽

Phage Display Libraries

AbstractAs the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to threaten public health worldwide, the development of effective interventions is urgently needed. Neutralizing antibodies (nAbs) have great potential for the prevention and treatment of SARS-CoV-2 infection. In this study, ten nAbs were isolated from two phage-display immune libraries constructed from the pooled PBMCs of eight COVID-19 convalescent patients. Eight of them, consisting of heavy chains encoded by the immunoglobulin heavy-chain gene-variable region (IGHV)3-66 or IGHV3-53 genes, recognized the same epitope on the receptor-binding domain (RBD), while the remaining two bound to different epitopes. Among the ten antibodies, 2B11 exhibited the highest affinity and neutralization potency against the original wild-type (WT) SARS-CoV-2 virus (KD = 4.76 nM for the S1 protein, IC50 = 6 ng/mL for pseudoviruses, and IC50 = 1 ng/mL for authentic viruses), and potent neutralizing ability against B.1.1.7 pseudoviruses. Furthermore, 1E10, targeting a distinct epitope on RBD, exhibited different neutralization efficiency against WT SARS-CoV-2 and its variants B.1.1.7, B.1.351, and P.1. The crystal structure of the 2B11–RBD complexes revealed that the epitope of 2B11 highly overlaps with the ACE2-binding site. The in vivo experiment of 2B11 using AdV5-hACE2-transduced mice showed encouraging therapeutic and prophylactic efficacy against SARS-CoV-2. Taken together, our results suggest that the highly potent SARS-CoV-2-neutralizing antibody, 2B11, could be used against the WT SARS-CoV-2 and B.1.1.7 variant, or in combination with a different epitope-targeted neutralizing antibody, such as 1E10, against SARS-CoV-2 variants.

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