{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T04:24:18Z","timestamp":1784175858469,"version":"3.55.0"},"reference-count":39,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,12,4]],"date-time":"2025-12-04T00:00:00Z","timestamp":1764806400000},"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>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>One of the main hurdles in solid tumors to the limited response of immunotherapy is the lack of sufficient T-cell infiltrate. This study aims to construct an iRGD-modified BiTE-directed T-cell therapeutic approach to enhance the treatment efficacy against KRAS G12V-mutated pancreatic cancer.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We used a novel bispecific T-cell engager (BiTE) targeting the HLA-A2\/KRAS G12V complex and CD3 (HLA-A2\/KRAS G12V-CD3 BiTE). By modifying with iRGD, we induced BiTE-mediated inward flow of activated effector T cells, specifically targeting the KRAS G12V mutation and improving tumor tissue penetration to address the problem of limited efficacy due to insufficient effector cells infiltration.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The results demonstrated that iRGD modification could promote tumor-specific lymphocyte infiltration and accumulation in tumor tissue, significantly inhibit tumor growth, and prolong survival in a xenograft pancreatic tumor model. This dual-action approach enhances T-cell infiltration by promoting transvascular and stromal penetration, greatly enhancing the efficacy of bispecific antibodies in solid tumors, leading to effective tumor eradication.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These findings strongly suggest further clinical validation of this iRGD-modified BiTE-directed T-cell therapeutic approach, potentially offering a more effective treatment option for patients with pancreatic cancer and other solid tumors.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2025.1693755","type":"journal-article","created":{"date-parts":[[2025,12,4]],"date-time":"2025-12-04T06:32:30Z","timestamp":1764829950000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Tumor-penetrating peptide boosts bispecific T-cell 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