Development of CAR-T Cells for T-ALL Targeting CCR9

Discover a groundbreaking webinar exploring the developments in cancer immunotherapy targeting CC chemokine receptor 9 (CCR9), a potential breakthrough for T-cell acute lymphoblastic leukemia (T-ALL). CCR9 is a potential cancer immunotherapy target, expressed in the majority of cases of T-ALL but only in a small proportion of normal immune and thymic cells. Thus, an immunotherapy targeted against CCR9 may be able to kill T-ALL cells while preserving critical normal T cells. GenScript has recently demonstrated that chimeric antigen receptor (CAR)-T cells targeting CCR9 were potent in in vitro and murine models of T-ALL and will shortly commence a Phase I clinical trial of anti-CCR9 CAR-T in relapsed or refractory T-ALL.

CCR9 is a complex and challenging target antigen. It is a G-protein coupled receptor with seven transmembrane domains. There is high homology between rodent and human sequences with most differences located intracellularly or at the amino terminus. Thus, developing specific antibodies to CCR9 is difficult, and a previous rat vaccination yielded only a single antibody clone.

In a new binder discovery campaign, multiple approaches were used to develop binders to CCR9, including DNA and RNA vaccination of both mice and rabbits. Despite initial challenges, several highly specific anti-CCR9 clones were obtained using RNA vaccination, with differing epitopes and biophysical characteristics. These clones are now being tested in antibody-drug conjugate and bispecific T-cell engager formats for potency in T-ALL and other conditions.

Further, using in silico design and experimental validation, optimized humanized versions of the initial anti-CCR9 antibody and single-chain fragment variable (scFv) which retained the binding characteristics and potency of the original clone were developed. Finally, using protein vaccination of rabbits, an anti-idiotype reagent to the original scFv, which will be used to track CAR-T in patients was developed.

Join this webinar to gain insights into advancements in T-ALL immunotherapy using CAR-T cells targeting the CCR9 receptor.

In this webinar, you will learn about:

CCR9 is a valid target for CAR-T therapy of T-cell acute lymphoblastic leukemia

The development of anti-CCR9 binders was challenging and required novel vaccination approaches

Anti-idiotype antibodies were generated for clinical monitoring

In this webinar, you will learn

Webinar Details

  • Date: Wednesday, March 06, 2024
  • Time: 11am EST (NA) / 4pm GMT (UK) / 5pm CET (EU-Central)
  • Speaker:
Dr. Paul Maciocia Dr. Paul Maciocia,

Clinical Scientist and Honorary Consultant Haematologist, Cancer Institute, University College London

Dr. Paul Maciocia is a Clinician Scientist and Consultant Haematologist at University College London in the UK. His academic and clinical practice is centred around chimeric antigen receptor (CAR) T cells. He undertook his PhD and postgraduate research in the laboratory of Dr. Martin Pule at UCL and now runs a research group with interests in CAR-T for T cell cancers, allogeneic ‘off the shelf’ CAR-T and synthetic biology approaches to improve CAR-T efficacy.
His work has directly led to three clinical trials of novel CAR-T and he is an inventor on several patents related to CAR-T. He is a recipient of multiple awards including the Royal College of Pathologist Gold Medal for research, the American and European Societies of Hematology Translational Research Training in Hematology award, an American Society of Gene and Cellular Therapy Excellence in Research award, the British Society of Blood and Bone Marrow Transplant John Goldman Scientific award and others.

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