Article Text

Download PDFPDF

437 Optimised achilles VELOSTM process 2b manufacturing platform generates a significant dose boost of reactive CD8 and CD4 clonal neoantigen-reactive T cells for the treatment of solid cancer
  1. Monica Sassi1,
  2. Sandro Gomez1,
  3. Evi Rologi1,
  4. Meghan Madigan1,
  5. Joanne Tang1,
  6. Sarah Thirkell1,
  7. Samuel Jide Banwo1,
  8. Temi Ogunleye1,
  9. Sophie McKeeman1,
  10. Claire Law1,
  11. Unnaamalai Meyyappan1,
  12. Eleni Kotsiou1,
  13. Katy Newton1,
  14. Theres Oakes1,
  15. Miha Kosmac1,
  16. Luke Goodsell1,
  17. Connor Carolan1,
  18. Justin Ahern1,
  19. Tim Hillyer1,
  20. Bongi Ndlovu1,
  21. Henrieta Fraser1,
  22. Sergio A Quezada1,2 and
  23. Edward Samuel1
  1. 1Achilles Therapeutics UK Ltd, London, UK
  2. 2University College London, London, UK
  • Journal for ImmunoTherapy of Cancer (JITC) preprint. The copyright holder for this preprint are the authors/funders, who have granted JITC permission to display the preprint. All rights reserved. No reuse allowed without permission.


Background Clonal neoantigens are formed early in cancer evolution and have been identified as a subset of patient specific mutations that are associated with improved clinical benefit, representing great promise as targets for next generation T cell therapies. Cell therapies targeting multiple clonal neoantigens represent a unique personalised approach to treating solid cancer, as they are present on all cancer cells, minimising the risk of tumour escape, and absent from healthy tissue. Process 2 of the VELOSTM manufacturing platform has successfully demonstrated the feasibility of generating clonal neoantigen-reactive T cell (cNeT) products for the treatment of advanced NSCLC, (NCT04032847) and melanoma (NCT03997474) in two first-in-human studies. Here we demonstrate that implementation of an optimised VELOSTM platform (Process 2b) in clinical manufacturing can generate a significant dose boost of highly potent and reactive CD8+ and CD4+ cNeT for clinical use compared to both Process 1 and Process 2.

Method Briefly, tumour-infiltrating lymphocytes (TIL) were isolated from tumour fragments and Dendritic Cells (DCs) generated from whole blood, prior to cryopreservation. Patient-specific clonal neoantigens were predicted using our proprietary PELEUSTM bioinformatic platform, enabling manufacture of synthetic peptides for each patient. The co-culture of TIL and peptide loaded DCs allows the selective expansion of cNeT, prior to a polyclonal T cell boost step.

Results Here we present clinical manufacturing data on 21 tumour samples (13 NSCLC and 8 melanoma) generated with Process 2b and demonstrate a 5-fold increase in the median CD3+ TIL yield compared to 33 TIL intermediates (13 NSCLC and 20 melanoma) generated with Process 2 (30M vs. 147M). Improvements in TIL yield at the pre-expansion step have driven a 10-fold increase in the median cNeT dose (17M vs. 167M) following co-culture in 15 clinical batches manufactured with VELOSTM Process 2b (14 – 6,347M) compared to 17 batches manufactured with Process 2 (1.4 – 6,409M). Median clonal reactivity was 16% (0.2 – 96%) with products manufactured with Process 2b compared to 10% (0 – 97.6%) with Process 2. Furthermore, peptide deconvolution identified products with multiple single T cell reactivities to clonal neoantigens demonstrating a highly polyclonal product (mean number of unique variants: 7, range 0 – 90).

Conclusions We demonstrate that optimised VELOSTM Process 2b incorporating the PELEUSTM platform for prediction of clonal neoantigens can generate significantly higher cNeT doses and in some cases >1B in concert with accurately identifying the active drug component for the treatment of advanced NSCLC and melanoma.

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.