ORIGINALLY PUBLISHED
27 April 2023
Written by:
Gavin M Bendle
Senior Vice President, Research and Development, Neogene
Eric Tran
Associate Member, Earle A. Chiles Research Institute, Providence Cancer Institute, and Expert Consultant for AstraZeneca (Head of TCR therapy, Oncology R&D)
Cell therapy in oncology has been spearheaded by the development of therapeutic chimeric antigen receptor (CAR)‑T cells, created by isolating and modifying a patient’s T cells to target their cancer.1 While this approach has transformed outcomes for patients with some blood cancers, effective CAR-T cell therapy for solid cancers is not yet a reality.1,2
Developing cell therapies to put cures within reach
The recent acquisition of Neogene Therapeutics by AstraZeneca gives us a unique opportunity to join forces and approach this challenge from multiple angles including:
- ‘Armoured’ CAR-Ts, designed to overcome the immunosuppressive barrier of the tumour microenvironment and increase their potential effectiveness in hard-to-treat solid tumours.
- T-cell receptor therapies (TCR-Ts) that can reach intracellular targets, including tumour-specific mutations, expanding the breadth of targets accessible by cell therapies.
Leading the way in targeting cancer with TCRs
Neogene was founded in 2018 and has rapidly grown into an international biotechnology company. As veterans of the development of life-changing CAR-T technology we’re using our decades of experience and deep expertise in TCR biology to expand the potential of cell therapy. Our focus is to discover, develop and manufacture transformative next-generation TCR‑Ts, to target cancer specific proteins (‘neoantigens’).
Neogene’ brings new expertise in TCR-T development that complements our in-house CAR-T capabilities, clinical research expertise and growing programme of off-the-shelf neoantigen-targeted therapies.
Exploiting the T-cell receptor in cancer treatment
The T-cell receptor (TCR) is a transmembrane receptor found on the surface of T cells that is responsible for recognising targets, or ‘antigens’ in the form of peptides bound to the major histocompatibility complex (MHC) on target cells.3 The MHC is a complex which collects and presents protein fragments (peptides), including those found within cancer cells, to the TCR, thereby activating T cells and stimulating an immune response.
Advances in genetic engineering have enabled scientists to use TCRs to edit the antigen-specificity of T cells, paving the way for the emergence of T-cell therapies that recognise tumour-specific, MHC-bound mutation-derived peptides.4 By leveraging the MHC antigen-recognition mechanism, TCR-Ts are able to identify a broad range of targets including intracellular proteins. This complements our emerging pipeline of CAR-Ts that recognise proteins expressed on the surface of cancer cells and unlocks new targets, expanding the potential to treat more tumour types.
Accelerating the development of TCR-Ts
Commonly occurring driver mutations in tumour cells are highly attractive targets for cell therapy since they are critical for cancer growth. Targeting these mutations provides a mechanism for selectively targeting cancer cells and limits the ability of tumour cells to evade attack by immune system. On this basis, the Neogene team are advancing TCR-Ts that target commonly occurring oncogenic driver mutations in solid tumours.
On the other hand, cancer is a highly individualised disease, caused by patient specific genetic changes which produce unique neoantigens. In addition to targeting common driver mutations, the Neogene team have created a proprietary platform to engineer TCR-Ts that recognise patient-specific neoantigens. Our discovery platform allows the rapid screening of large patient derived TCR libraries to identify multiple neoantigen-specific TCRs from a patient, from which fully individualised, multi-specific TCR-T therapies can be created, thereby enabling a multi-pronged attack of tumour cells.
Looking to the future
Bringing Neogene into our Company brings leading infrastructure to the development of this revolutionary new approach in cell therapy. Our complementary skills will help us to overcome practical barriers and reach patients with hard-to-treat cancers in the clinic.
We look forward to accelerating our research in this field, with the potential to bring curative cell therapies to a larger number of patients and move the oncology paradigm from ‘treat’ to ‘cure’.
Join us as we continue to explore the future of oncology
We welcome committed, talented scientists to join us in creating the future of oncology cell therapy. we recruit scientists with relevant expertise to join us in our state-of-the-art research facilities in Cambridge, UK, and Gaithersburg, US; and Neogene are looking to expand their dynamic, high-achieving teams in Amsterdam, The Netherlands and Santa Monica, US.
