- New data highlight the strength and versatility of Leucid’s proprietary, next-generation technology
- pCAR has now achieved proof-of-concept across a range of co-stimulatory domains, binders, targets and target combinations in pre-clinical liquid and solid tumour cell lines/models
- John Maher has been an early pioneer of CAR T-cell immunotherapy with a focus on solid tumours
London, UK – 16 March 2022 – Leucid Bio (“Leucid” or the “Company”), a biotech company pioneering next-generation cell therapies for hard-to-treat cancers, today notes the publication of two studies in Cell Reports Medicine and Frontiers in Immunology co-authored by its Chief Scientific Officer John Maher.
The research reinforces the conclusion that Leucid’s leading technology, parallel CAR (pCAR), has now achieved proof-of-concept across a range of co-stimulatory domains, binders, targets and target combinations in pre-clinical liquid and solid tumour cell lines/models. Professor Maher’s technical and scientific expertise in advancing CARs that harness lessons of nature to deliver greater functional persistence is a key driver behind Leucid’s technology platform. Leucid’s LEU-011 programme is a NKG2D-targeted pCAR T-cell therapy in pre-clinical development for the treatment of solid tumours and haematological malignancies. LEU-011 has potential for the treatment of multiple cancer types as NKG2D ligands are expressed on more than 80% of human tumour cells.
John Maher, Chief Scientific Officer of Leucid Bio, noted: “Our findings confirm that Juxta-membrane localisation is required for effective CAR-mediated co-stimulation and that our proprietary resulting pCAR configurations promote functional persistence of T-cells. As a result, pCAR T-cells have a role in mediating enhanced anti-tumour activity. The data also reinforces the evidence that our pCAR platform delivers enhanced anti-tumour activity through effective provision of dual co-stimulation. pCAR has now been proven across a range of constructs and targets and Leucid is in a leading position to leverage these findings.”
Artin Moussavi, Chief Executive Officer of Leucid Bio, added: “John’s latest research provides further evidence of the great potential of pCAR and these papers and the accompanying work underpin the activities of the Company and especially the imminent clinical trial. John has been a pioneer in the CAR-T space for decades, and his prolific publication record speaks volumes to his prominence in the field. These recently published studies highlight the strength of the translational research done at John’s CAR Mechanics research group and Leucid Bio. I am honored to work with John in translating his findings into patient-driven outcomes.”
John Maher has been an early pioneer of CAR T-cell immunotherapy with 100 research papers published over the last three decades. He developed a novel CAR structure, pCAR, in which two co-stimulatory domains are integrated in parallel across the cell membrane. This formation replicates the natural side-by-side position of these molecules across the cell membrane that is seen in endogenous immune receptors. The resulting pCAR T-cells consistently outperform previous generations of CAR T-cells. Professor Maher also worked on the adapter CAR which simulates the configuration adopted by many naturally occurring immune receptors in which the binding and signalling domains are physically separated onto two or more proteins. Leucid’s experience has been that this architecture is also compatible with the engineering of CARs with substantial anti-tumour activity.
The recently published papers are as follows:
- “Synergistic T cell signalling by 41BB and CD28 is optimally achieved by membrane proximal positioning within parallel chimeric antigen receptors” – Published on 21 December 2021 in Cell Reports Medicine.
Designed pCARs to evaluate whether effective dual co-stimulation requires juxta-membrane positioning of endodomain components within separate synthetic receptors. The study demonstrated that the pCAR platform optimally harnesses synergistic and tumour-dependent co-stimulation to resist T-cell exhaustion and senescence, sustaining proliferation, cytokine release, cytokine signalling, and metabolic fitness upon repeated stimulation. When engineered using targeting moieties of diverse composition, affinity, and specificity, pCAR T-cells consistently elicit superior anti-tumour activity compared with T-cells that express traditional linear CARs.
- “Engineering of an Avidity-Optimized Q1 CD19-Specific Parallel Chimeric Antigen Receptor That Delivers Dual CD28 and 4-1BB Co-Stimulation” – Published on 20 January 2022 in Frontiers in Immunology.
Evaluated dual co-stimulation through pCAR architecture using CD28-containing second generation CAR and co-expressing with a 4-1BB containing chimeric co-stimulatory receptor. These CAR and pCAR T-cells were engineered to specifically target CD19 and demonstrated a broad range of CD19 binding ability and avidity for CD19-expressing tumour cells, a significant enhancement of tumour re-stimulation potential and IL-2 release as well as reduced exhaustion marker expression and enhanced therapeutic efficacy when compared to second generation CARs.
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