{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T18:06:49Z","timestamp":1789754809723,"version":"4.0.1"},"reference-count":52,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T00:00:00Z","timestamp":1789689600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      pTTL is produced by\n                      <jats:italic>in vitro<\/jats:italic>\n                      expansion of T cells from RLNs using EpiTCer\u00ae 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\u00ae. Selected neoantigen epitopes are included in recombinantly produced proteins and attached to paramagnetic EpiTCer\u00ae micro-particles, forming the tumour-selective T cell stimulus TC0301 used in pTTL manufacturing. The trial comprises three parts:\n                      <jats:bold>Part I<\/jats:bold>\n                      includes sequencing of tumour and blood samples, RLNs collection, TC0301 production and pTTL manufacturing.\n                      <jats:bold>Part II<\/jats:bold>\n                      includes preconditioning, pTTL administration and 26 weeks follow-up, and\n                      <jats:bold>Part III<\/jats:bold>\n                      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 10\n                      <jats:sup>6<\/jats:sup>\n                      \u20131 x 10\n                      <jats:sup>9<\/jats:sup>\n                      cells, the entire pTTL yield will be administered.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>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\u00ae and EpiTCer\u00ae 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Trial registration<\/jats:title>\n                    <jats:p>\n                      Authorized under the Clinical Trial Regulation (Regulation EU No 536\/2014), EU CT #2024-512296-13-00.\n                      <jats:bold>ClinicalTrials.gov ID<\/jats:bold>\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/clinicaltrials.gov\/ct2\/show\/NCT05908643\" xlink:type=\"simple\">NCT05908643<\/jats:ext-link>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0351697","type":"journal-article","created":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T17:26:10Z","timestamp":1789752370000},"page":"e0351697","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"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"],"prefix":"10.1371","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-8851-4220","authenticated-orcid":true,"given":"Ahmed","family":"Tarfy","sequence":"first","affiliation":[{"name":"Uppsala","place":["University, Sweden"],"department":["Department of surgical sciences"]},{"name":"Centre for clinical research V\u00e4stmanland, Uppsala University","place":["V\u00e4ster\u00e5s, Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Salm\u00e9n","sequence":"additional","affiliation":[{"name":"Neogap Therapeutics AB","place":["Stockholm, Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guro","family":"Gafvelin","sequence":"additional","affiliation":[{"name":"Neogap Therapeutics AB","place":["Stockholm, Sweden"]},{"name":"Karolinska Institutet","place":["Stockholm, Sweden"],"department":["Department of Clinical Neuroscience (CNS)"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans","family":"Gr\u00f6nlund","sequence":"additional","affiliation":[{"name":"Neogap Therapeutics AB","place":["Stockholm, Sweden"]},{"name":"Karolinska Institutet","place":["Stockholm, Sweden"],"department":["Department of Clinical Neuroscience (CNS)"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abbas","family":"Chabok","sequence":"additional","affiliation":[{"name":"Centre for clinical research V\u00e4stmanland, Uppsala University","place":["V\u00e4ster\u00e5s, Sweden"]},{"name":"Danderyd Hospital, Karolinska Institutet","place":["Stockholm, Sweden"],"department":["Department of Clinical Sciences, Division of Surgery"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5949-3810","authenticated-orcid":true,"given":"Maziar","family":"Nikberg","sequence":"additional","affiliation":[{"name":"Uppsala","place":["University, Sweden"],"department":["Department of surgical sciences"]},{"name":"Centre for clinical research V\u00e4stmanland, Uppsala University","place":["V\u00e4ster\u00e5s, Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0438-5887","authenticated-orcid":true,"given":"Per J.","family":"Nilsson","sequence":"additional","affiliation":[{"name":"Karolinska Comprehensive Cancer Center, Karolinska University Hospital","place":["Stockholm, Sweden"],"department":["Medical Unit Pelvic Cancer - 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