{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T18:23:54Z","timestamp":1785435834211,"version":"3.56.0"},"reference-count":28,"publisher":"American Society for Microbiology","issue":"7","license":[{"start":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T00:00:00Z","timestamp":1784592000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T00:00:00Z","timestamp":1784592000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"Cue Biopharma"},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01AI030048"],"award-info":[{"award-number":["R01AI030048"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P01AI056299"],"award-info":[{"award-number":["P01AI056299"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2026,7,21]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      Interleukin-2 (IL-2) remains an attractive cytokine for enhancing antigen-specific CD8 T-cell responses in cancer immunotherapy, but systemic toxicity hinders its broad clinical application. To address this, various IL-2-based therapeutics have been engineered with altered IL-2 receptor bias or targeted delivery to tumors, the tumor microenvironment, or immune cell populations. Ideally, IL-2 signals should be selectively delivered to antigen-specific CD8 T cells, boosting their responses and promoting effector differentiation while sparing non-targeted populations. Immuno-STAT (Selective Targeting and Alteration of T cells) is a fusion protein platform comprising a bivalent peptide-major histocompatibility complex (MHC) class I complex and an affinity-attenuated IL-2 mutein that co-stimulates T-cell receptor and IL-2 signaling in epitope-specific CD8 T cells. Here, we investigated whether a D\n                      <jats:sup>b<\/jats:sup>\n                      GP\n                      <jats:sub>33-41<\/jats:sub>\n                      -targeted Immuno-STAT enhances D\n                      <jats:sup>b<\/jats:sup>\n                      GP33-specific CD8 T-cell responses in a mouse model of chronic lymphocytic choriomeningitis virus infection. Immuno-STAT treatment selectively expanded D\n                      <jats:sup>b<\/jats:sup>\n                      GP33-specific CD8 T cells with an effector-like phenotype. Non-targeted D\n                      <jats:sup>b<\/jats:sup>\n                      GP276-specific CD8 T cells showed little to no expansion in response to D\n                      <jats:sup>b<\/jats:sup>\n                      GP\n                      <jats:sub>33-41<\/jats:sub>\n                      -targeted Immuno-STAT therapy, underscoring the selectivity of this approach. However, minor changes in phenotypic markers, including increased expression of CD25 and CX3CR1, were observed in non-targeted CD8 T cells, likely reflecting bystander IL-2 signaling. Combining Immuno-STAT with PD-1 blockade augmented D\n                      <jats:sup>b<\/jats:sup>\n                      GP33-specific CD8 T-cell responses more effectively than PD-1 blockade alone, with minor effects on the non-targeted D\n                      <jats:sup>b<\/jats:sup>\n                      GP276-specific population. These findings inform the clinical development of Immuno-STAT and other IL-2 therapeutics and highlight the value of coordinated TCR and IL-2 stimulation during chronic antigen exposure, alone or in combination with PD-1 blockade.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>IMPORTANCE<\/jats:title>\n                    <jats:p>Interleukin-2 (IL-2) is a key cytokine for promoting effector differentiation of antigen-specific CD8 T cells and remains an attractive agent in cancer immunotherapy, but systemic toxicity limits its clinical use. This study addresses a central challenge in IL-2-based immunotherapy: delivering IL-2 to cognate antigen-specific CD8 T cells while minimizing activation of non-targeted populations. Using a mouse model of chronic lymphocytic choriomeningitis virus (LCMV) infection, we show that the Immuno-STAT (Selective Targeting and Alteration of T cells) platform selectively expands targeted virus-specific CD8 T cells and enhances their function while limiting effects on non-targeted populations. We also show that combining Immuno-STAT with PD-1 blockade further enhances targeted virus-specific CD8 T-cell responses during chronic LCMV infection. These findings provide mechanistic and preclinical support for integrating T-cell receptor specificity with IL-2 signaling to advance cancer immunotherapy and guide next-generation IL-2 therapeutics for cancer and chronic infection.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/jvi.00593-26","type":"journal-article","created":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T13:00:42Z","timestamp":1781528442000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["Simultaneous TCR and IL-2 agonism selectively enhances epitope-specific CD8 T-cell responses during chronic viral infection"],"prefix":"10.1128","volume":"100","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7120-1390","authenticated-orcid":true,"given":"Masao","family":"Hashimoto","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03czfpz43","id-type":"ROR","asserted-by":"publisher"}],"name":"Emory Vaccine Center, 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