A Big BiTE: Tetravalent BiTE Highly Potent in HER2-positive Breast Cancer Models

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A tetravalent BiTE against HER2 and CD3 showed potent antitumor activity in models of HER2-positive cancer, supporting further clinical development.
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.”

Read more of Cancer Therapy Advisor's coverage of the ESMO 2018 meeting by visiting the conference page.

Reference

  1. 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.

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