KEY TAKEAWAYS
- The phase I trial aimed to develop B4t2-001, a CAR-T therapy that can differentiate between normal and malignant cells in solid tumors.
- The PrismCore generated CAR-T cells by computational design and experimental validation.
- The study found that B4t2-001 was a promising CAR-T therapy for solid tumors that targets BT-001.
The future of CAR-T therapy depends on developing CAR-T cells that can differentiate between normal and malignant cells. Researchers aimed to develop B4t2-001, a CAR-T therapy that can differentiate between normal and malignant cells in solid tumors.
The PrismCore employed computational biology and empirical insights to develop CAR-T cells, utilizing synthetic single-domain antibodies and structural/signaling components to construct prototype CAR libraries. The bio-screening with combinatorial libraries was generated through computational simulations. They identified leading CAR-T candidates through iterative in vitro and in vivo testing, followed by safety evaluations in non-human primates (NHPs).
The study identified engineered T cells targeting self-antigens, and the first CAR-T, named B4t2-001, has progressed to clinical trials against the BT-001 target. They designed, synthesized, and assessed camelid antibody libraries ranging from 1E10 to 1E11. Selected antibody variants were combined into CAR-T cells and rigorously screened against BT-001. About 6 promising candidates underwent further testing in mice to assess their anti-tumor effects and sustained in vivo activity. B4t2-001 was evaluated in NHPs expressing basal levels of BT-001, showing no toxicity despite detectable circulating CAR-T cells and in vitro activity against NHP BT-001 at high density. The turnaround time from target selection to clinical evaluation of B4t2-001 was six months.
The study found that B4t2-001 was a promising CAR-T therapy for solid tumors that targets BT-001.
Source: https://ascopubs.org/doi/abs/10.1200/JCO.2023.41.16_suppl.2540?af=R
Clinical Trial: https://clinicaltrials.gov/study/NCT05621486
Farzad Haerizadeh, Helena Jiang, and Laurence Cooper.DOI: 10.1200/JCO.2023.41.16_suppl.2540 Journal of Clinical Oncology 41, no. 16_suppl (June 01, 2023) 2540-2540.
