Sartorius #2 eBook - 2019 - 12

Importance of mAb Discovery and Development in Immunotherapy

The first generation of bsAbs was developed through methods including chemical
cross-linking or from hybridomas. Currently, bsAbs are generated by chemical
conjugation with cross-linkers, by somatic fusion of two hybridoma lines (quadroma),
and by genetic (protein/cell) engineering.
More recently, bsAb developers have created such antibodies with Fc regions. These
bsAbs can mediate Fc effector functions, such as antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity and have the half-lives of normal
IgGs. Alternatively, bsAbs without the Fc region (bispecific fragments) rely solely on
their antigen-binding capacity for carrying out therapeutic activity.
Due to their smaller size, these fragments have better solid-tumor penetration rates,
but they are also rapidly cleared from circulation leading to shorter in vivo half-lives.
Now scientists can adjust the size, valency, flexibility, and half-life of bsAbs to suit
the application.
Competing in the bsAb Market
Last year, Roots Analysis issued a report entitled, "Bispecific Antibody Therapeutics
Market (3rd Edition), 2017-2030." The report observed that that about 11 technology
platforms are currently in extensive use. These include Dual Affinity Re-targeting
(DART) (MacroGenics), Bispecific T-cell Engager (BiTE) (Amgen), CrossMAb (Roche),
Nanobody (Ablynx), and XmAb (Xencor).
Many bsAb candidates are BiTE antibodies that have been developed such that one
antigen-binding site is directed against the CD3 receptor on cytotoxic T lymphocytes,
while the other antigen-binding site is directed against specific tumor-cell antigens
(such as CD19, CD20, CD33, CD123, HER2, epithelial cell adhesion molecule [EpCAM],
BCMA, CEA, and others).
The ability to bind two or more unique epitopes gives bsAbs greater versatility than
conventional mAbs because they can target multiple pathways, cross-link cell surface
receptors, pretarget oncological epitope-containing cell types, deliver therapeutics
12 |

GENengnews.com
http://www.GENengnews.com
Sartorius #2 eBook - 2019

Table of Contents for the Digital Edition of Sartorius #2 eBook - 2019
