Current progress in innovative engineered antibodies

Abstract

As of May 1, 2017, 74 antibody-based molecules have been approved by a regulatory authority in a major market. Additionally, there are 70 and 575 antibody-based molecules in phase III and phase I/II clinical trials, respectively. These total 719 antibody-based clinical stage molecules include 493 naked IgGs, 87 antibody-drug conjugates, 61 bispecific antibodies, 37 total Fc fusion proteins, 17 radioimmunoglobulins, 13 antibody fragments, and 11 immunocytokines. New uses for these antibodies are being discovered each year. For oncology, many of the exciting new approaches involve antibody modulation of T-cells. There are over 80 antibodies in clinical trials targeting T cell checkpoints, 26 T-cell-redirected bispecific antibodies, and 145 chimeric antigen receptor (CAR) cell-based candidates (all currently in phase I or II clinical trials), totaling more than 250 T cell interacting clinical stage antibody-based candidates. Finally, significant progress has been made recently on routes of delivery, including delivery of proteins across the blood-brain barrier, oral delivery to the gut, delivery to the cellular cytosol, and gene- and viral-based delivery of antibodies. Thus, there are currently at least 864 antibody-based clinical stage molecules or cells, with incredible diversity in how they are constructed and what activities they impart. These are followed by a next wave of novel molecules, approaches, and new methods and routes of delivery, demonstrating that the field of antibody-based biologics is very innovative and diverse in its approaches to fulfill their promise to treat unmet medical needs.

Perspectives of Fc engineered antibodies in CD19 targeting immunotherapies in pediatric B-cell precursor acute lymphoblastic leukemia

“…1 Breakthroughs were achieved by the bispecific T cell engager (BiTE) antibody blinatumomab and chimeric antigen receptors for genetic engineering of T cells (CAR T cells). 2 Promising results were also obtained with novel CD19 antibodies that were optimized by Fc engineering to enhance their therapeutic efficacy in recent years.…”

Prediction of methionine oxidation risk in monoclonal antibodies using a machine learning method

“…Protein-based therapeutics are widely recognized for their potential 1,2 in treating a range of diseases, with almost a quarter of the biopharmaceutical product approvals in the past 20 years being monoclonal antibodies (mAbs). 3 In addition to possessing the desired antigen affinity and specificity, the successful therapeutic antibody development candidate needs to meet favorable developability criteria, 4 such as an optimal in vivo clearance profile, low aggregation propensity, and high levels of physical (thermal/pH) and chemical stability.…”

A systematic approach for analysis and characterization of mispairing in bispecific antibodies with asymmetric architecture

“…1-3 As of 2017, ~ 60 bispecific antibodies were in clinical studies, 4 and two have received approval from the US Food and Drug Administration: blinatumomab (Blincyto®; Amgen/Micromet) and emicizumab-kxwh (Hemlibra® Chugai/Genentech). The more than 100 bispecific antibody formats that have been reported in the literature 5,6 can be divided into three categories.…”