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643 A first in human phase I/IIa trial of personalized tumor-trained lymphocytes, pTTL, derived from regional lymph nodes for treatment of colorectal cancer
  1. Sofia Berglund1,2,
  2. Anne-Laure Joly1,2,
  3. Erwan Le Maitre1,2,
  4. Kelly Day2,
  5. Luigi Notari1,2,
  6. Claudia Carvalho-Queiroz2,
  7. Ola Nilsson1,2,
  8. Andreas Kaiser1,2,
  9. Maximilian Kordes3,
  10. Jeffrey Yachnin3,
  11. Mattias Carlsten1,4,
  12. Stephan Mielke1,4,
  13. Abbas Chabok5,
  14. Maziar Nikberg5,
  15. Ahmed Salim Tarfy5,
  16. Andrea Salmén2,
  17. Samuel Svensson2,
  18. Hanjing Xie1,2,
  19. Guro Gafvelin1,2 and
  20. Hans Grönlund1,2
  1. 1Karolinska Institutet, Stockholm, Sweden
  2. 2Neogap Therapeutics AB, Stockholm, Sweden
  3. 3Karolinska University Hospital, Solna, Sweden
  4. 4Karolinska University Hospital, Huddinge, Sweden
  5. 5Centre for Clinical Research of Uppsala University, Västmanlands hospital Västerås, Västerås, Sweden
  • 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 The new generation of adoptive T cell therapy utilizing high-precision neoantigen targeting is gaining increasing interest, especially in solid tumors, where the unmet medical need is high. Personalized tumor trained lymphocytes (pTTL) is a novel autologous adoptive T cell therapy targeting patient-specific neoantigens. A phase I/IIa First in Human (FIH) clinical trial of pTTL in Stage IV colorectal cancer (CRC) patients has started 2023.

Methods pTTL is produced through in vitro expansion of T cells derived from tumor-adjacent regional lymph nodes (RLN). The T cells are stimulated with a patient-specific array of neoantigens utilizing the proprietary EpiTCer® technology. Tumor-specific mutations are identified from next generation sequencing data obtained from tumor and normal tissue samples, and personal neoantigen epitopes are selected and ranked using the in-house bioinformatic software PIOR®. Polypeptides containing the selected neoantigens are designed, produced and linked to paramagnetic micro-particles to form EpiTCer® beads, a tumor-selective T cell expansion stimulus used for pTTL manufacturing.

Results pTTL can be manufactured with a high rate of success despite the product’s personalized nature. pTTL consists mainly of T cells, with small proportions of NK and B cells. The CD4/CD8 T cell ratio varies between products. pTTL contains a significant proportion of memory T cells expressing markers indicating functionality, with limited levels of late-stage T cells. TCR sequencing has demonstrated increased T cell clonality in pTTL compared to in the RLN starting material, indicating antigen-specific expansion.

Conclusions The ongoing FIH Phase I/II trial will include up to 16 patients with Stage IV CRC. pTTL is administered as a single-dose monotherapy after chemotherapy-based preconditioning with cyclophosphamide and fludarabine. A dose-escalation design is applied.

The trial is divided into three parts. Part I: Collection of materials for sequencing and pTTL production (tumour biopsy, surgical collection of RLNs), and manufacturing of EpiTCer® beads and pTTL. Part II: pre-conditioning, administration of pTTL and follow-up for 6 months. Part III: Long-term follow-up to 5 years after pTTL administration.

The primary endpoint is safety. Secondary outcomes include response, overall survival, and progression-free survival. Biomarkers for pTTL persistence, pTTL characteristics, and response will be evaluated.

Trial Registration Trial Registration EUDRA CT #2022–000394-96. Identifier #NCT05908643

Ethics Approval The trial is approved by the Swedish MPA (5.1–2022-89272) and the Swedish Ethical Review Authority (2022–01842-01). All patients must give their informed consent to participation before inclusion in the trial.

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

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