p95HER2-T cell bispecific antibody for breast cancer treatment

Area of Science:

• Oncology
• Immunotherapy
• Molecular Biology

Background:

• T cell bispecific antibodies (TCBs) engage T cells to target cancer.
• HER2 is a tumor antigen in ~25% of breast cancers, but HER2 TCBs cause toxicity due to normal tissue expression.
• p95HER2, a HER2 fragment, is found in ~40% of HER2-positive tumors and not in normal tissues.

Purpose of the Study:

• To develop and evaluate a TCB targeting the tumor-specific antigen p95HER2.
• To assess the safety and efficacy of p95HER2-TCB in preclinical models of breast cancer.

Main Methods:

• Development of a novel TCB targeting p95HER2.
• In vitro and in vivo testing of p95HER2-TCB efficacy and specificity.
• Comparison of p95HER2-TCB with a HER2-targeting TCB.

Main Results:

• p95HER2 is specifically expressed on tumor cells and not normal tissues.
• p95HER2-TCB demonstrated potent antitumor activity against p95HER2-expressing primary breast cancers and brain metastases.
• p95HER2-TCB showed no activity against non-transformed cells lacking HER2 overexpression, unlike HER2-TCB.

Conclusions:

• Targeting p95HER2 with TCBs is a viable strategy for treating a subset of HER2-positive breast cancers.
• p95HER2-TCB offers a potentially safer therapeutic option by exploiting a tumor-specific antigen.
• This approach may overcome the toxicities associated with targeting broadly expressed antigens like HER2.