Origene_Jan2021_ProperAntibodyDesignKeeps - 18

Bispecific, Multispecific Antibodies Grapple with Cancer

Bispecific, Multispecific
Antibodies Grapple with Cancer
Platforms for novel antibody constructs take hold in
cancer immunotherapy development
By Ian C. Clift, PhD, Scientific Communications Consultant, Biomedical
Associates and Clinical Assistant Professor, Indiana University

C

ancer immunotherapy has been advancing

to show their limitations, they should be recognized

on several fronts, most strikingly in the

as part of a sequence of antibody-based cancer

direction of checkpoint inhibition and

immunotherapy developments, a sequence that

chimeric antigen receptor (CAR) T-cell therapy.

reaches back at least as far as the Nobel Prize-

Another front, however, is about to see its share of

winning efforts of James P. Allison, PhD, and Tasuku

action. Here, newly engineered bispecific and multi-

Honjo, MD, PhD. Allison's work on the CTLA-4 led to

specific antibodies will be put to the test. Such anti-

the first FDA-approved checkpoint inhibitor drug,

bodies may engage two or more antigens at once,

ipilimumab (Yervoy, Bristol-Myers Squibb), whereas

serving as force multipliers that can exploit oppor-

Honjo's discovery of PD-1 led to the development of

tunities beyond the reach of monospecific anti-

anti-PD-1 drugs such as pembrolizumab (Keytruda,

bodies, whether they are deployed solo or in teams.

Merck). These drugs and other checkpoint inhibitors

Although monospecific antibodies are beginning

have profoundly impacted the treatment of cancer.
An alternative cancer immunotherapy approach,

Need to get customized
antibodies??

namely CAR T-cell therapy, has also demonstrated

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cells are engineered to launch sustained attacks

its potential to combat cancer. In this approach, T
on tumors. Although CAR T-cell therapies clearly
have fight in them, they may cede some anticancer
glory to bispecific antibodies (bsAbs). The first

GO

FDA-approved bsAb to directly compete with CAR-T
was the CD19/CD3 drug blinatumomab (Blincyto,
Amgen). It was introduced in 2014 for indications in
B-cell precursor acute lymphoblastic leukemia.

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