ESGCT 2021 OR54: Multicentre, prospective research protocol for development of a clonal neoantigen-reactive T cell therapy pipeline across multiple tumour types:
October 22, 2021 at 07:44 am EDT
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Multicentre, prospective research protocol for development of a clonal neoantigen- reactive T cell therapy pipeline across multiple tumour types
M Grant, T Hou, F Kyle, K Miller, J Robinson, A Rogers, M Werner Sunderland, E Kotsiou, B Samways, P Kotecha, H Patel, N Charlaftis, S Kaur Lally, S Jide- Banwo, E Rologi, M Pruchniak, M Epstein, M Saggese, KR Newton, S Patel, S Quezada
Cancer cells accumulate mutations in their DNA over time. Many of the mutations lead to changes in the proteins encoded by the mutated genes, which can then be recognised by the immune system as 'foreign'
These cancer-specific 'neo-antigens' can potentially be exploited by immunotherapies such as Adoptive Cell Therapy (ACT) and Checkpoint Inhibitors (CPIs)
The mutations occurring before the initial cancer transformation event are carried by all of the cells of the growing cancer and are known as 'clonal' mutations
Mutations that subsequently occur are known as 'subclonal' mutations and are not present in all of the cancer cells, hence these are less likely to produce complete response, i.e. the elimination of the whole cancer cell population
TIL has delivered long-termdurable disease control in multiple solid tumor settings1-4
T cell expansion is non-specific with no control over which antigens are targeted and the approach results in subclonal targeting, reducing chances of complete disease control
Requires very high (non- physiological) levels of IL-2 that result in T cell exhaustion and reduced anti-tumor activity5
Red: clonal neoantigens
Purple, green and orange: subclonal
neoantigens
Clonal Neo-antigen Reactive T Cell (cNeT)
Ability to measure antigen-specific potency and monitor antigen-specific T cell engraftment and expansion
Provides precision targeting of clonal neoantigens shown to correlate with the anti-tumor activity of TIL6 and checkpoint inhibitors7
Clonal neoantigen targeting provides a means to target all the tumor cells
Using dendritic cells to drive T cell expansion reduces the need for IL-2 expansion, producing a fitter T cell
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Achilles Therapeutics plc published this content on 22 October 2021 and is solely responsible for the information contained therein. Distributed by Public, unedited and unaltered, on 22 October 2021 11:43:04 UTC.
Achilles Therapeutics plc is a United Kingdom-based clinical-stage immuno-oncology biopharmaceutical company. The Company is engaged in developing precision T cell therapies to treat multiple types of solid tumors. Its lead product is a precision tumor-derived T cell therapy targeting clonal cancer neoantigens. Its pipeline includes Chiron: Advanced Non-Small Cell Lung Cancer, Thetis: Melanoma (Monotherapy), Thetis: Melanoma (PD-1 Combination), and other indications. It is focused on advancing cancer therapies through its work in the field of tumor evolution. Its platform enables to identify mutations formed early in the development of a cancer that give rise to antigens that are expressed by all of a patient's cancer cells but are absent from healthy tissue. It refers to this class of solid tumor targets as clonal neoantigens. To identify clonal neoantigens in a patient, it has developed a bioinformatic platform called PELEUS.
ESGCT 2021 OR54: Multicentre, prospective research protocol for development of a clonal neoantigen-reactive T cell therapy pipeline across multiple tumour types
ACHILLES THERAPEUTICS PLC 
