A Bispecific Antibody (BsAb), an artificial antibody by connection of two mAbs, can simultaneously bind to two different antigens, or two different epitops. At Wuhan YZY Biopharma we have developed an asymmetrical BsAb platform called YBODY® (see the Figure ) with one arm binding to a specific protein of a cancer cell (a target site) and the other arm binding to CD3 on T-cell (an effector site). The binding of CD3 activates the T-cell, pulls the T-cell close to the cancer cell, and thus, enhances killing the cancer cell by the T cell. As its advantage as bellow (or linked to advantage), BsAbs have become the most attractive biologics for cancer therapy.
In addition to one target and one effector(e.g. M802, M701), YBODY® can be also manufactured for functional other formats: (1) different targets of the cancer cell, in such way YBODY® can block two complementary signal pathways or increase the affinity to the targeted cells to decrease the negative effects. (2) one target and one drug to deliver the drug direct to the targeted cells.
Current applications of BsAb have been explored for cancer immunotherapy and drug delivery. Two products including Blinatumomab (Blincyto, Amgen) and Catumaxomab (Trion Pharma) have been marked on USA in 2014 and Europe in 2009, respectively. Up to the end of 2017, total of more than 60 BsAb have been for the clinical phase I-III, among which more than 40 in phase I, 18 in phase II, and 2 in phase III. More is expected for going to be clinical trials.
1、Whole IgG: PK /PD and bioprocess similar to a mAb
2、Fc with Knob-in-hole and salt bridges: high heterodimer production with limited homodimers
3、CD3 scFv format: ideal for T redirected BsAb
4、Unique MOA: high potency with reduce in recurrence
5、Low dosage: largely reduce side effects and production cost
6、Platform: expandable to variety of targets and effectors