Episode 63: Engineering of acidic pH-responsive anti-CD3 binding antibodies

About this episode

This episode discusses the engineering of anti-CD3 binding antibodies that respond to acidic pH in the tumor microenvironment to improve cancer immunotherapy.

**Monday Immune Engager** — our weekly pick from the latest immune-engager digest. **Paper:** [Engineering of acidic pH-responsive anti-CD3 binding antibodies](https://doi.org/10.1080/19420862.2026.2658902) **Authors:** Grégory La Sala, Katharina B. Kroell, Mudita Pincha, Christian Gassner, et al. **Journal:** mAbs, 2026 **Why it matters:** Tumor-selective T-cell engagers could dramatically reduce the on-target, off-tumor toxicity that limits current CD3-directed cancer immunotherapies. **Summary** T-cell engagers are bispecific antibodies that physically tether a cytotoxic T-cell to a tumor cell by simultaneously binding a tumor-associated antigen and the CD3 receptor complex — the master activation switch of T-cells. The problem is that CD3-binding potency is indiscriminate: if the target antigen appears even at trace levels on healthy tissue, activated T-cells will attack it. This paper from Roche exploits a well-characterized feature of the tumor microenvironment — a local pH of roughly 6.5–6.8 driven by lactic acid accumulation and poor vascular clearance, versus the tightly regulated systemic pH of 7.4 — to engineer anti-CD3 antibodies that bind avidly inside a tumor but…

People in this episode

Host: Raymond Ruff

Topics covered

• T-cell engagers
• cancer immunotherapy
• pH-responsive antibodies
• tumor microenvironment
• bispecific antibodies

Keywords

• anti-CD3 antibodies
• tumor-selective
• T-cell activation
• cancer treatment
• pH-sensitive
• immunotherapy
• bispecific antibodies

Mentioned in this episode

Organizations: Roche

Books & works: Engineering of acidic pH-responsive anti-CD3 binding antibodies, mAbs

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