Title: The Complete Guide to Classifications of Bispecific Antibodies
1The Complete Guide to Classifications of
Bispecific Antibodies
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2Introduction
Ordinary tumor therapeutic antibodies can only
bind to a single antigen with a relatively low
binding specificity is relatively low, which is
prone to off-target effects.
Bispecific antibodies (bsAbs) can recognize and
bind two different antigens separately, so it can
connect immune cells, viral molecules, etc. to
tumor cells, thereby enhancing the killing effect
on target cells
3Bispecific antibody without C region
01
CONTENTS
Bispecific antibody containing C region
02
Bispecific antibodies containing non-antibody
fragments
03
41 Bispecific antibody without C region
Such BsAbs contain only variable segments of
antibody molecules, and thus their structures
differ greatly from those of general antibodies,
and can also be referred to as bispecific
antibodies of non-IgG-like structures. It retains
only the fragments that bind to the antigen and
the relative molecular mass is usually small, so
it has a high tissue permeability and easily
penetrates into the tumor tissue through the
blood vessels.
However, low molecular mass also results in a
short half-life in plasma, so the use of this
drug for anti-tumor therapy requires continuous
intravenous infusion of a constant-flow pump or
in a sustained-release dosage form.
52 Bispecific antibody containing C region
The structure of this constant region-containing
BsAbs is very similar to that of a general
antibody structure, and is also called a
bispecific antibody of an IgG-like structure. It
differs from the general IgG antibody and
non-IgG-like structure of bsAbs in that it has
both bispecificity and the corresponding function
of the constant region, and its relatively large
molecular weight, so it has higher stability and
longer half-life.
And it is also beneficial for the purification of
antibody products, but its tissue permeability is
also relatively low. Different types can be
formed depending on the different domains of the
fusion, such as scFv-Fc antibody, Minibody,
Bi-nanobody and the like.
63 Bispecific antibodies containing non-antibody
fragments
Some special non-antibody structures contained in
some bispecific antibodies also play a certain
role. For example, owing to the small molecular
mass, some BsAbs have faster plasma clearance
rate and shorter residence time in tumor tissues,
which ultimately reduces their efficacy. Some
researchers have linked some molecules in BsAbs
by chemical ligation to increase their relative
molecular mass, prolong their half-life, and thus
improve their efficacy, such as linking
polyethylene glycol (PEG), serum albumin and
albumin binding groups.
PEG is a polymer that increases the relative
molecular mass of BsAbs and reduces its renal
filtration rate. But in some cases, it may cause
partial inactivation or decrease affinity of
antibody fragments. In addition, it can also
enhance the efficacy by connecting some drug
molecules, such as diphtheria toxin, ricin,
acacia toxin and so on.
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