A first-in-human, phase I/IIa trial of the T cell immunotherapy personalised tumour trained lymphocytes in patients with advanced colorectal cancer: Study protocol
8 affiliations
- 1Department of surgical sciences, UppsalaUniversity, Sweden
- 2Centre for clinical research Västmanland, Uppsala University, Västerås, Sweden
- 3Neogap Therapeutics AB, Stockholm, Sweden
- 4Department of Clinical Neuroscience (CNS), Karolinska Institutet, Stockholm, Sweden
- 5Department of Clinical Sciences, Division of Surgery, Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden
- 6Medical Unit Pelvic Cancer - Colorectal Cancer, Karolinska Comprehensive Cancer Center, Karolinska University Hospital, Stockholm, Sweden
- 7Medical Unit Cell Therapy and Allogeneic Stem cell Transplantation (ME CAST), Karolinska Comprehensive Cancer Center, Karolinska University Hospital, Stockholm, Sweden
- 8Phase I-unit, Centre for Clinical Cancer Studies, Karolinska Comprehensive Cancer Center, Karolinska University Hospital, Stockholm, Sweden
Abstract
Background: Adoptive T cell therapy is a promising alternative to conventional therapies for certain solid tumours. Personalized tumour-trained lymphocytes (pTTL) is an autologous T cell therapy derived from tumour-draining regional lymph nodes (RLNs), trained to target patient-specific neoantigens arising from tumour-specific mutations. The protocol for an ongoing phase I/IIa first-in-human trial of pTTL in Stage IV Colorectal Cancer (CRC), NEOGAP-CRC-01, is presented here. Methods: pTTL is produced by in vitro expansion of T cells from RLNs using EpiTCer® technology. Tumour-specific neoantigen-forming mutations are identified through next-generation sequencing of tumour and blood samples and the most optimal neoantigens are selected using the bioinformatics software PIOR®. Selected neoantigen epitopes are included in recombinantly produced proteins and attached to paramagnetic EpiTCer® micro-particles, forming the tumour-selective T cell stimulus TC0301 used in pTTL manufacturing. The trial comprises three parts: Part I includes sequencing of tumour and blood samples, RLNs collection, TC0301 production and pTTL manufacturing. Part II includes preconditioning, pTTL administration and 26 weeks follow-up, and Part III consists of up to five years follow-up after pTTL administration. Up to 16 patients can be included. pTTL is administered as a single-dose infusion following preconditioning with cyclophosphamide and fludarabine. Between the limits of 20 x 106–1 x 109 cells, the entire pTTL yield will be administered. Discussion: pTTL represents a novel approach within adoptive T-cell therapy, using autologous T cells trained to target selected neoantigens without genetic modification. The integration of PIOR® and EpiTCer® technology enables individualized neoantigen identification and delivery. Interpretation of treatment efficacy may be challenging due to the highly personalized nature of pTTL and the heterogeneity of CRC. The primary trial endpoint is safety. Secondary endpoints include objective treatment response, overall survival, and progression-free survival. Biomarkers of pTTL persistence, product characteristics, and treatment response will be assessed. Trial registration: Authorized under the Clinical Trial Regulation (Regulation EU No 536/2014), EU CT #2024-512296-13-00. ClinicalTrials.gov ID NCT05908643
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BibTeX
@article{tarfy2026firstinhuman,
title = {{A first-in-human, phase I/IIa trial of the T cell immunotherapy personalised tumour trained lymphocytes in patients with advanced colorectal cancer: Study protocol}},
author = {Ahmed Tarfy and Andrea Salmén and Guro Gafvelin and Hans Grönlund and Abbas Chabok and Maziar Nikberg and Per J. Nilsson and Mattias Carlsten and Maximilian Kordes and Sofia Berglund},
journal = {PLOS One},
year = {2026},
month = sep,
doi = {10.1371/journal.pone.0351697},
url = {https://doi.org/10.1371/journal.pone.0351697},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - A first-in-human, phase I/IIa trial of the T cell immunotherapy personalised tumour trained lymphocytes in patients with advanced colorectal cancer: Study protocol
AU - Ahmed Tarfy
AU - Andrea Salmén
AU - Guro Gafvelin
AU - Hans Grönlund
AU - Abbas Chabok
AU - Maziar Nikberg
AU - Per J. Nilsson
AU - Mattias Carlsten
AU - Maximilian Kordes
AU - Sofia Berglund
PY - 2026
DA - 2026/09/18
JO - PLOS One
DO - 10.1371/journal.pone.0351697
UR - https://doi.org/10.1371/journal.pone.0351697
AB - Background: Adoptive T cell therapy is a promising alternative to conventional therapies for certain solid tumours. Personalized tumour-trained lymphocytes (pTTL) is an autologous T cell therapy derived from tumour-draining regional lymph nodes (RLNs), trained to target patient-specific neoantigens arising from tumour-specific mutations. The protocol for an ongoing phase I/IIa first-in-human trial of pTTL in Stage IV Colorectal Cancer (CRC), NEOGAP-CRC-01, is presented here. Methods: pTTL is produced by in vitro expansion of T cells from RLNs using EpiTCer® technology. Tumour-specific neoantigen-forming mutations are identified through next-generation sequencing of tumour and blood samples and the most optimal neoantigens are selected using the bioinformatics software PIOR®. Selected neoantigen epitopes are included in recombinantly produced proteins and attached to paramagnetic EpiTCer® micro-particles, forming the tumour-selective T cell stimulus TC0301 used in pTTL manufacturing. The trial comprises three parts: Part I includes sequencing of tumour and blood samples, RLNs collection, TC0301 production and pTTL manufacturing. Part II includes preconditioning, pTTL administration and 26 weeks follow-up, and Part III consists of up to five years follow-up after pTTL administration. Up to 16 patients can be included. pTTL is administered as a single-dose infusion following preconditioning with cyclophosphamide and fludarabine. Between the limits of 20 x 106–1 x 109 cells, the entire pTTL yield will be administered. Discussion: pTTL represents a novel approach within adoptive T-cell therapy, using autologous T cells trained to target selected neoantigens without genetic modification. The integration of PIOR® and EpiTCer® technology enables individualized neoantigen identification and delivery. Interpretation of treatment efficacy may be challenging due to the highly personalized nature of pTTL and the heterogeneity of CRC. The primary trial endpoint is safety. Secondary endpoints include objective treatment response, overall survival, and progression-free survival. Biomarkers of pTTL persistence, product characteristics, and treatment response will be assessed. Trial registration: Authorized under the Clinical Trial Regulation (Regulation EU No 536/2014), EU CT #2024-512296-13-00. ClinicalTrials.gov ID NCT05908643
SN - 1932-6203
ER -