{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,25]],"date-time":"2025-10-25T00:33:52Z","timestamp":1761352432383,"version":"3.41.2"},"reference-count":31,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,6,17]],"date-time":"2024-06-17T00:00:00Z","timestamp":1718582400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Chimeric antigen receptor T (CAR-T) cell therapies have achieved remarkable success in the treatment of hematological tumors. However, given the distinct features of solid tumors, particularly heterogeneity, metabolic aggressiveness, and fewer immune cells in tumor microenvironment (TME), the practical utility of CAR-T cells for solid tumors remains as a challenging issue. Meanwhile, although anti-PD-1 monoclonal antibody (mAb) has shown clinical efficacy, most mAbs also show limited clinical benefits for solid tumors due mainly to the issues associated with the lack of immune cells in TME. Thus, the infiltration of targeted immunological active cells into TME could generate synergistic efficacy for mAbs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We present a combinational strategy for solid tumor treatment, which combines armored-T cells to express Fc-gamma receptor I (Fc\u03b3RI) fragment on the surfaces for targeting various tumors with therapeutically useful mAbs. Choosing CD20 and HER-2 as the targets, we characterized the <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic> efficacy and latent mechanism of the combination drug by using flow cytometry, ELISA and other methods.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The combination and preprocessing of armored T-cells with corresponding antibody of Rituximab and Pertuzumab exerted profound anti-tumor effects, which is demonstrated to be mediated by synergistically produced antibody-dependent cellular cytotoxicity (ADCC) effects. Meanwhile, mAb was able to carry armored-T cell by preprocessing for the infiltration to TME in cell derived xenograft (CDX) model.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>This combination strategy showed a significant increase of safety profiles from the reduction of antibody doses. More importantly, the present strategy could be a versatile tool for a broad spectrum of cancer treatment, with a simple pairing of engineered T cells and a conventional antibody.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2024.1400177","type":"journal-article","created":{"date-parts":[[2024,6,17]],"date-time":"2024-06-17T04:45:22Z","timestamp":1718599522000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Broadening anticancer spectrum by preprocessing and treatment of T- lymphocytes expressed Fc\u03b3RI and monoclonal antibodies for refractory cancers"],"prefix":"10.3389","volume":"15","author":[{"given":"Lei","family":"Tang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qinyi","family":"Sun","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mengyuan","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoxiao","family":"Yu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jinguo","family":"Meng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yun","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuxiao","family":"Ma","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aizhong","family":"Zeng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhuolan","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuanyuan","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xinyu","family":"Xu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Guo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2024,6,17]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1186\/s40364-023-00537-x","article-title":"The CAR macrophage cells, a novel generation of chimeric antigen-based approach against solid tumors","volume":"11","author":"Hadiloo","year":"2023","journal-title":"biomark Res"},{"key":"B2","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1186\/s12943-023-01723-z","article-title":"CAR-cell therapy in the era of solid tumor treatment: current challenges and emerging therapeutic advances","volume":"22","author":"Maalej","year":"2023","journal-title":"Mol Cancer"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.782775","article-title":"Chimeric antigen receptor T-cell therapy in lung cancer: potential and challenges","volume":"12","author":"Xiao","year":"2021","journal-title":"Front Immunol"},{"key":"B4","doi-asserted-by":"publisher","first-page":"140","DOI":"10.1186\/s13287-022-02819-x","article-title":"Hurdles to breakthrough in CAR T cell therapy of solid tumors","volume":"13","author":"Marofi","year":"2022","journal-title":"Stem Cell Res Ther"},{"key":"B5","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1016\/j.cell.2020.03.001","article-title":"The emerging landscape of immune cell therapies","volume":"181","author":"Weber","year":"2020","journal-title":"Cell"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.3390\/cancers15061836","article-title":"Inflammation, infiltration, and evasion-tumor promotion in the aging breast","volume":"15","author":"Cruz-Reyes","year":"2023","journal-title":"Cancers (Basel)"},{"key":"B7","doi-asserted-by":"publisher","first-page":"101079","DOI":"10.1016\/j.tranon.2021.101079","article-title":"Novel antigens of CAR T cell therapy: New roads; old destination","volume":"14","author":"Safarzadeh Kozani","year":"2021","journal-title":"Transl Oncol"},{"key":"B8","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1186\/s40364-023-00482-9","article-title":"New cell sources for CAR-based immunotherapy","volume":"11","author":"Mazinani","year":"2023","journal-title":"biomark Res"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2014.00520","article-title":"IgG subclasses and allotypes: from structure to effector functions","volume":"5","author":"Vidarsson","year":"2014","journal-title":"Front Immunol"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-09-179754","article-title":"Specificity and affinity of human Fcgamma receptors and their polymorphic variants for human IgG subclasses","volume":"113","author":"Bruhns","year":"2009","journal-title":"Blood"},{"key":"B11","doi-asserted-by":"publisher","first-page":"114411","DOI":"10.1016\/j.ab.2021.114411","article-title":"Antigen improves binding of IgGs to Fc\u03b3Rs in SPR analysis","volume":"640","author":"Wang","year":"2022","journal-title":"Anal Biochem"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22073349","article-title":"Delivery of orally administered digestible antibodies using nanoparticles","volume":"22","author":"Tashima","year":"2021","journal-title":"Int J Mol Sci"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2567.1999.00884.x","article-title":"Acidic pH increases the avidity of FcgammaR for immune complexes","volume":"98","author":"L\u00f3pez","year":"1999","journal-title":"Immunology"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1100499","article-title":"Fc\u03b3RI FG-loop functions as a pH sensitive switch for IgG binding and release","volume":"14","author":"Lu","year":"2023","journal-title":"Front Immunol"},{"key":"B15","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1186\/s12929-021-00709-7","article-title":"pH-responsive antibodies for therapeutic applications","volume":"28","author":"Klaus","year":"2021","journal-title":"J BioMed Sci"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-21-0407","article-title":"A phase I trial of regional mesothelin-targeted CAR T-cell therapy in patients with Malignant pleural disease, in combination with the anti-PD-1 agent pembrolizumab","volume":"11","author":"Adusumilli","year":"2021","journal-title":"Cancer Discovery"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2022007317","article-title":"Anti-CD19 CAR T cells in combination with ibrutinib for the treatment of chronic lymphocytic leukemia","volume":"6","author":"Gill","year":"2022","journal-title":"Blood Adv"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.21.01676","article-title":"Long-term follow-up of combination of B-cell maturation antigen and CD19 chimeric antigen receptor T cells in multiple myeloma","volume":"40","author":"Wang","year":"2022","journal-title":"J Clin Oncol"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2019.09.006","article-title":"Combination immunotherapy with CAR T cells and checkpoint blockade for the treatment of solid tumors","volume":"36","author":"Grosser","year":"2019","journal-title":"Cancer Cell"},{"key":"B20","doi-asserted-by":"publisher","first-page":"281","DOI":"10.3892\/ol","article-title":"Combination of CAR\u2212T cell therapy and radiotherapy: Opportunities and challenges in solid tumors (Review)","volume":"26","author":"Zhong","year":"2023","journal-title":"Oncol Lett"},{"key":"B21","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1186\/s12951-023-01900-8","article-title":"CD16 CAR-T cells enhance antitumor activity of CpG ODN-loaded nanoparticle-adjuvanted tumor antigen-derived vaccinevia ADCC approach","volume":"21","author":"Zhang","year":"2023","journal-title":"J Nanobiotechnology"},{"key":"B22","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1038\/s41416-018-0341-1","article-title":"High-affinity CD16-polymorphism and Fc-engineered antibodies enable activity of CD16-chimeric antigen receptor-modified T cells for cancer therapy","volume":"120","author":"Rataj","year":"2019","journal-title":"Br J Cancer"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2017.00457","article-title":"FC\u03b3 Chimeric receptor-engineered T cells: methodology, advantages, limitations, and clinical relevance","volume":"8","author":"Caratelli","year":"2017","journal-title":"Front Immunol"},{"key":"B24","doi-asserted-by":"publisher","first-page":"103941","DOI":"10.1016\/j.ebiom.2022.103941","article-title":"Improving CAR-T immunotherapy: Overcoming the challenges of T cell exhaustion","volume":"77","author":"Gumber","year":"2022","journal-title":"EBioMedicine"},{"key":"B25","doi-asserted-by":"publisher","first-page":"112797","DOI":"10.1016\/j.celrep.2023.112797","article-title":"T lymphocytes expressing the switchable chimeric Fc receptor CD64 exhibit augmented persistence and antitumor activity","volume":"42","author":"Cui","year":"2023","journal-title":"Cell Rep"},{"key":"B26","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1158\/0008-5472.CAN-13-1365","article-title":"T lymphocytes expressing a CD16 signaling receptor exert antibody-dependent cancer cell killing","volume":"74","author":"Kudo","year":"2014","journal-title":"Cancer Res"},{"key":"B27","doi-asserted-by":"publisher","first-page":"792","DOI":"10.1158\/2326-6066.CIR-22-0423","article-title":"T cells expressing a modified fc\u03b3RI exert antibody-dependent cytotoxicity and overcome the limitations of CAR T-cell therapy against solid tumors","volume":"11","author":"Rasoulouniriana","year":"2023","journal-title":"Cancer Immunol Res"},{"key":"B28","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1186\/s40364-022-00434-9","article-title":"Strategies to enhance CAR-T persistence","volume":"10","author":"Liu","year":"2022","journal-title":"biomark Res"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-08-4597","article-title":"Strongly enhanced antitumor activity of trastuzumab and pertuzumab combination treatment on HER2-positive human xenograft tumor models","volume":"69","author":"Scheuer","year":"2009","journal-title":"Cancer Res"},{"key":"B30","doi-asserted-by":"publisher","first-page":"R61","DOI":"10.1186\/bcr3674","article-title":"Construction and evaluation of a novel humanized HER2-specific chimeric receptor","volume":"16","author":"Sun","year":"2014","journal-title":"Breast Cancer Res"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-22-1276","article-title":"A novel autologous CAR-T therapy, YTB323, with preserved T-cell stemness shows enhanced CAR T-cell efficacy in preclinical and early clinical development","volume":"13","author":"Dickinson","year":"2023","journal-title":"Cancer Discovery"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2024.1400177\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,17]],"date-time":"2024-06-17T04:45:28Z","timestamp":1718599528000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2024.1400177\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,6,17]]},"references-count":31,"alternative-id":["10.3389\/fimmu.2024.1400177"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2024.1400177","relation":{},"ISSN":["1664-3224"],"issn-type":[{"type":"electronic","value":"1664-3224"}],"subject":[],"published":{"date-parts":[[2024,6,17]]},"article-number":"1400177"}}