The Chain: Protein Engineering Podcast Episode: 83 - Patrick Baeuerle and Jeffrey Miller on T Cell and Immune Cell Engagement
Mar 17, 2026
Jeffrey Miller, physician‑scientist advancing NK cell therapies and tri‑specific NK engagers. Patrick Baeuerle, biotech entrepreneur behind T‑cell bispecifics and peptide‑MHC work. They compare T cell and NK engagers to CAR T approaches. Topics include conditional tumor selectivity, IL‑15 and NK activation, peptide‑MHC targeting, manufacturing and clinical strategies, and use in MRD and neoadjuvant settings.
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Patrick's Portfolio Spans Autoimmunity AML And pMHC Engagers
- Patrick Baeuerle described multiple programs at Cullinan: CLN978 (CD19×CD3) for autoimmune disease, CLN049 (FLT3×CD3) for AML, and a BCMA×CD3 licensed for autoimmune development.
- He also highlighted Crossbow's CB250 pMHC engager as an example of company-building across modalities.
NK Therapies Offer Safety But Trail T Cells By Years
- NK-cell therapeutics lag T-cell therapies by years but offer a favorable safety profile and potential for allogeneic off-the-shelf use.
- Jeffrey Miller emphasized his goal to achieve an FDA-approved NK therapy within five to ten years, noting manufacturing and clinical hurdles.
T-Cell Engagers Show Lower Severe Toxicity And Less Exhaustion
- T-cell engagers tend to cause less severe CRS and neurotoxicity than CAR T-cells and are less prone to exhaustion because they recruit broad endogenous T-cell populations.
- Baeuerle cited meta-analyses and Blinatumomab data showing lower grade ≥3 CRS/ICANS and expansion of effector-memory T cells.