A Big BiTE: Tetravalent BiTE Highly Potent in HER2-Positive Breast Cancer Models
A tetravalent BiTE against HER2 and CD3 showed potent antitumor activity in models of HER2-positive cancer, supporting further clinical development.
|The following article features coverage from the European Society for Medical Oncology (ESMO) 2018 meeting. Click here to read more of Cancer Therapy Advisor's conference coverage.|
The tetravalent bispecific T-cell engaging (BiTE) antibody ABP-100 demonstrated potent antitumor activity against HER2-positive cancer models with a similar safety profile as bivalent molecules, according to a study that will be presented at the ESMO 2018 Congress in Munich, Germany.1
Given the success of chimeric antigen T-cell (CAR-T) therapy, BiTE antibodies offer an alternative approach to directing T cells to tumor cells. This study evaluated the activity of a trivalent BiTE, constructed to have 2 binding sites each for HER2 and CD3. Most other BiTEs are bivalent, binding only once to each target.
The tetravalent BiTE antibody ABP-100 demonstrated stronger binding with HER2 than the traditional monovalent approach, but the structure of ABP-100 resulted in a functionally monovalent binding of CD3.
Treatment of in vitro and in vivo models of HER2-positive cancer with ABP-100 resulted in highly potent antitumor activity, with complete responses occurring at low doses, with no evidence of recurrence after treatment discontinuation.
ABP-100 efficacy was dependent on HER2 expression. Combination treatment consisting of ABP-100 and an anti-PD-L1 antibody demonstrated a synergistic effect.
The safety profile of ABP-100 was similar to that of a bivalent anti-HER2 BiTE.
The authors concluded that the tetravalent structure may result in a larger therapeutic index than bivalent molecules. The authors stated that, “these data support the clinical development of ABP-100 in HER2-positive tumors.”
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- Boudot A, Huang X, Murphy S, et al. ABP-100: A tetravalent bispecific T-cell engaging antibody for HER2+ solid tumors. Presented at: the ESMO 2018 Congress; Munich, Germany: October 19-23, 2018. Abstract 1170P.