{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T20:03:40Z","timestamp":1769803420526,"version":"3.49.0"},"reference-count":78,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T00:00:00Z","timestamp":1769731200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003196","name":"Ministero della Salute","doi-asserted-by":"publisher","award":["5x1000 project 2025 5M-2022-2365490, 2020 5xMILR19 -12006-0053"],"award-info":[{"award-number":["5x1000 project 2025 5M-2022-2365490, 2020 5xMILR19 -12006-0053"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Anti-GD2 monoclonal antibody effectively treats high-risk neuroblastoma (HR-NB) by recruiting NK cells for antibody-dependent cellular cytotoxicity (ADCC). We recently developed a cell product containing mature, cytotoxic \u03b3\u03b4 T and NK cells (GADEKILL), and its potential use as a novel immunotherapy for HR-NB has been investigated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The GADEKILL \u03b3\u03b4 T and NK cells were analyzed by flow cytometry for the expression of activating and inhibitory receptors and for cytotoxicity against NB, both with and without dinutuximab-\u03b2, at a 1:1 effector-to-target ratio. NB cell lines with high and low\/absent GD2 expression, as well as patient-derived 3D tumor spheres, all GD2-expressing, were used as targets. Comparative analyses were performed between GADEKILL NK and purified NK cells obtained from the same donor leukapheresis. Furthermore, a panel of NB cell lines was tested for the expression of B7H6 (i.e., NKp30 ligand), Human influenza hemagglutinin-tag (HA-TAG) and calreticulin (i.e., NKp46 ligands), and butyrophilin (BTN)2A1 and BTN3A1\/2\/3 (i.e., TCRV\u03b42 ligands), and the impact on GADEKILL cytotoxicity was assessed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Compared to their purified counterparts, GADEKILL NK cells showed: (i) higher expression of NKp30 and NKp44 and lower expression of CD16 and NKG2D, (ii) greater cytotoxicity (CD107a\n                      <jats:sup>+<\/jats:sup>\n                      ) against GD2\n                      <jats:sup>\u2212<\/jats:sup>\n                      NB cells, (iii) stronger induction of lysis in low GD2-expressing NB cells and patient-derived 3D tumor spheres, and (iv) comparable ADCC. In addition, both \u03b3\u03b4 T and NK cells degranulated and consistently induced lysis in a panel of NB cell lines and patient-derived 3D tumor spheres expressing B7H6, calreticulin, HA-TAG, BTN2A1, and BTN3A1\/2\/3 consistently. Finally, NB cell lysis positively correlated with B7H6 and BTN2A1, and B7H6-blocking experiments revealed a significant decrease in target cell lysis when cells highly expressing B7H6 were used as targets.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our study demonstrated the potential antineuroblastoma activity of the GADEKILL, supporting its therapeutic use, particularly in the context of relapsed\/refractory R\/R HR-NB with low GD2 expression.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1755500","type":"journal-article","created":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T06:43:50Z","timestamp":1769755430000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["The gamma delta T\/NK cell product GADEKILL as a novel immunotherapeutic tool for neuroblastoma patients: role of B7H6 and BTN2A1 in tumor cell killing"],"prefix":"10.3389","volume":"17","author":[{"given":"Fabio","family":"Morandi","sequence":"first","affiliation":[{"name":"UOSD Laboratory of Cell Therapies, IRCCS Istituto Giannina Gaslini","place":["Genova, Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martina","family":"Della Lastra","sequence":"additional","affiliation":[{"name":"UOSD Laboratory of Cell Therapies, IRCCS Istituto Giannina Gaslini","place":["Genova, Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fabio","family":"Pastorino","sequence":"additional","affiliation":[{"name":"UOSD Laboratory of Experimental Therapies in Oncology, IRCCS Istituto Giannina Gaslini","place":["Genova, Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eleonora","family":"Ciampi","sequence":"additional","affiliation":[{"name":"UOSD Laboratory of Experimental Therapies in Oncology, IRCCS Istituto Giannina Gaslini","place":["Genova, Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maura","family":"Faraci","sequence":"additional","affiliation":[{"name":"Hematopoietic Stem Cell Transplantation Unit, IRCCS Istituto Giannina Gaslini","place":["Genova, Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chiara","family":"Brignole","sequence":"additional","affiliation":[{"name":"UOSD Laboratory of Experimental Therapies in Oncology, IRCCS Istituto Giannina Gaslini","place":["Genova, Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefano","family":"Giardino","sequence":"additional","affiliation":[{"name":"Hematopoietic Stem Cell Transplantation Unit, IRCCS Istituto Giannina Gaslini","place":["Genova, Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Irma","family":"Airoldi","sequence":"additional","affiliation":[{"name":"UOSD Laboratory of Cell Therapies, IRCCS Istituto Giannina Gaslini","place":["Genova, 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