Abstract:
:Since the turn of the century, cancer therapy has undergone a transformation in terms of new treatment modalities and renewed optimism in achieving long-lived tumor control and even cure. This is, in large part, thanks to the widespread incorporation of monoclonal antibodies (mAbs) into standard treatment regimens. These new therapies have, across many settings, significantly contributed to improved clinical responses, patient quality of life and survival. Moreover, the flexibility of the antibody platform has led to the development of a wide range of innovative and combinatorial therapies that continue to augment the clinician's armory. Despite these successes, there is a growing awareness that in many cases mAb therapy remains suboptimal, primarily due to inherent limitations imposed by the immune system's own homeostatic controls and the immunosuppressive tumor microenvironment. Here, we discuss the principal barriers that act to constrain the tumor-killing activity of antibody-based therapeutics, particularly those involving antibody glycans, using illustrative examples from both pre-clinical and market approved mAbs. We also discuss strategies that have been, or are in development to overcome these obstacles. Finally, we outline how the growing understanding of the biological terrain in which mAbs function is shaping innovation and regulation in cancer therapeutics.
journal_name
Glycobiologyjournal_title
Glycobiologyauthors
Dalziel M,Beers SA,Cragg MS,Crispin Mdoi
10.1093/glycob/cwy043subject
Has Abstractpub_date
2018-09-01 00:00:00pages
697-712issue
9eissn
0959-6658issn
1460-2423pii
5003042journal_volume
28pub_type
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