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Your Position: Home > News > Next wave of antibody development: Bispecific antibody and antibody drug conjugate (ADC)
Next wave of antibody development: Bispecific antibody and antibody drug conjugate (ADC)
Release time: 2021-02-16 Source: ACROBiosystems Read: 1231

As the first therapeutic antibody, OKT-3,  launched in 1986, more and more therapeutic monoclonal antibodies(mAb) have entered the clinical stage and gone to the market. The therapeutic monoclonal  antibodies have become an effective targeted treatment for cancer, viral  infection, and autoimmune diseases. However, in cancer and autoimmune diseases,  multiple signal pathways need to be blocked simultaneously to avoid  compensatory effects. In viral infections, similarly, we use cocktail therapy to avoid ineffectiveness caused by the viral mutation. On the other hand, mAb  can only bind to a single target and exert a single biological activity. They  are not able to satisfy those requirements mentioned above. With the  advancement of antibody engineering technology, bispecific antibodies and  antibody-drug conjugates will be the next wave of antibody research.


 Bispecific  antibody

Bispecific antibodies can simultaneously  bind to two different epitopes or antigens to block/activate dual target  signaling pathways. This induces immune cells to better kill tumor cells due to  the synergistic effects. Therefore, a bispecific antibody is better than a mAb  or even a combination of two mAbs. Besides cancers, bispecific antibodies are  also used in the treatment of osteoporosis, hemophilia, and autoimmune  diseases.

ADC1.jpg
     Figure 1 Structures of bispecific  antibodies and the mechanism of action


Bispecific antibodies draw more and more  attention these years. So far, more than 100 bispecific antibody structures  were reported. More than 150 bispecific antibodies are in the clinical stage,  and more than 400 are in the preclinical research. Bispecific antibodies can be  divided into three categories based on their structures:

     1. the structures without Fc fragment (such  as Blincyto);
     2. the asymmetric structures with Fc  fragment;
     3. the symmetrical structures with Fc  fragment. (The binding epitope of the second antibody is fused to the heavy or  light chain of the first antibody to recognize a second target. scFv is the  most common one.)

 

EGFR
VEGF
PD-1
GITR
TIM-3
LAG-3
BTLA
CD27
CD73
TGFbeta
DLL4
VEGFR2
ANGPT2
IL-6
HGF
cMET
HER3
LGR5
ICOS
CTLA-4
CD47
HER2
4-IBB
HIV-1 Env
CD4
CD32B
CD79B
CD20
CD95
TfR
BACE1
Tau
EGFRvIII
PD-L1
CD133
EpCAM
CLEC12
TROP2
CEA
FLT3
CD19
CD22
Claudin 18.2
GPC3
5T4
PSMA
CD28
FAP
MSLN
CD40
TA-MUC1
B7-H3
IL-13Ra2
GPA33
MUC16
Epha2
Cadherin-17
TRAIL R2
BCMA
NKp30
CD16
CD30
CD33
CD33
CD123
ROR1
CD38
IGF-I R
PSCA
DLL3
OX40
CD3


Click to find more bispecific antibody targets


Antibody-Drug  Conjugate

(ADC) is a conjugation of a highly targeted antibody drug and a  powerful chemo drug. ADC can accurately deliver drugs into tumor cells to avoid  the killing of normal cells, thereby reducing the adverse effects of chemo  drugs. The first ADC drug, Mylotarg, was approved as early as 2000. However,  the outbreak of ADC research didn’t come until 2019. So far, there are 9 drugs  on the market, 5 of which were approved simply in 2019. According to the  forecasts of Evaluate Pharma and BCG, the market size of ADC is expected to  reach US$12.9 billion globally in 2024.



ADC2.jpg

Figure 3 Classical ADC mode of action  (Chinese antibody society)


ADC drugs are mainly used in cancer  treatments. Due to a limited number of antigens on the surface of tumor cells,  the amount of drug delivered to tumor cells is relatively low. Therefore, the  choice of target antigens is crucial. The criteria for ADC target selection are  the same as for monoclonal antibody drugs. Ideally, the target is required to  be only on the surface of tumor cells with limited or no expression in normal  tissues. Meanwhile, it can have a certain rate of endocytosis and a suitable  route of endocytic transport.


The tumor-killing effects of ADC drugs  mainly rely on chemo drug molecules. The target is to bind the antibody and  bring the chemo drug into the cancer cells by endocytosis. Whether or not the  target has a biological effect is not critical. Therefore, compared with mAbs,  ADC drugs have more target options.


ADC3.jpg


     Figure  4 ADC targets for solid tumors


With a strong team of scientists, ACROBiosystems also  provides high-quality  integrated SPR&BLI analytical services. ACRO has served and  collaborated with more than 200 customers from academia and industry. Our work  supported multiple antibody drugs IND applications.
     
     
Click to learn more about SPR /BLI analytical service


Promotion
BsAb and ADCs affinity testing service

Promotion period: Jan.1-Mar.1,2021
ACRO proteins supplied free
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Case Study

Antibody binding with target protein

Herceptin (Trastuzumab) captured on CM5 chip via anti-human IgG Fc antibodies surface, can bind Human Her2, His Tag (Cat. No. HE2-H5225) with an affinity constant of 1.07 nM as determined in a SPR assay.

BsAb binding with Fc receptor protein


Learn more

Reference:
     Development of bispecific antibodies in  China: overview and prospects.
     Biology drives the discovery of bispecific antibodies  as innovative therapeutics.
     British Journal of Cancer, 2016

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