Francisco Conesa Buendía: AstraZeneca’s $1B Bet on In Vivo CAR-T – A Potential Game-Changer for Cancer Therapy
Francisco Conesa Buendía, Assistant in Cell and Gene Therapies Manufacturing at Memorial Sloan Kettering Cancer Center, shared a post on LinkedIn:
“AstraZeneca’s $1B Bet on In Vivo CAR-T: A Potential Game-Changer for Cancer Therapy.
The cell & gene therapy (CGT) field is evolving, and AstraZeneca is leading the way with a $1B acquisition of EsoBiotec, marking a major leap for in vivo CAR-T therapies. Unlike conventional CAR-T, which requires extracting and engineering T cells, EsoBiotec’s ESO-T01 modifies T cells inside the patient’s body, simplifying and accelerating the treatment process.
ESO-T01: In Vivo BCMA CAR-T:
ESO-T01 targets BCMA, a well-established multiple myeloma marker, by delivering genetic instructions directly to T cells via a proprietary engineered immune-shielded viral gene delivery system. This allows the patient’s immune system to generate cancer-fighting CAR-T cells without ex vivo manipulation.
How ESO-T01 Works:
- BCMA-Specific CAR Design (for information purpose, undisclosed).
Target: BCMA+ myeloma cells
CAR Structure:
Single-chain variable fragment (scFv) → Recognizes BCMA
CD3ζ domain → Triggers T-cell activation
Costimulatory domain (likely 4-1BB or CD28) → Enhances persistence and expansion - Gene Delivery:
ESO-T01 uses an engineered nanobodies LV approach (ENaBL)
Engineering tools:
Immune shielded engineered LV particles - Targeted In Vivo T-Cell Modification:
Genetic material integrates into circulating T cells, not all body cells
Ensures efficient uptake and high transduction efficiency
Uses T-cell-specific promoters to minimize off-target effects - Lymphodepletion-Free Therapy:
No chemotherapy preconditioning required
Efficient in vivo T-cell expansion ensures strong CAR-T response
Lower toxicity, better patient experience
Fast & Potent Response:
In an investigator-initiated trial, multiple myeloma cells became undetectable in bone marrow within 28 days.
Why ESO-T01 Matters:
- Lower costs.
- Faster treatment → No long production delays.
- More scalable & accessible → Administered in standard clinics.
- Reduced side effects → No chemo-based lymphodepletion.
Could in vivo CAR-T be the next breakthrough in oncology? Let’s discuss!”
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