{"id":32914,"date":"2025-05-19T18:47:24","date_gmt":"2025-05-19T16:47:24","guid":{"rendered":"https:\/\/inmuno.es\/index.php\/2025\/05\/19\/tcr-based-therapy-directed-against-kallikrein-related-peptidase-4-is-safe-and-effective-against-prostate-cancer\/"},"modified":"2025-05-19T18:47:24","modified_gmt":"2025-05-19T16:47:24","slug":"tcr-based-therapy-directed-against-kallikrein-related-peptidase-4-is-safe-and-effective-against-prostate-cancer","status":"publish","type":"post","link":"https:\/\/inmuno.es\/index.php\/2025\/05\/19\/tcr-based-therapy-directed-against-kallikrein-related-peptidase-4-is-safe-and-effective-against-prostate-cancer\/","title":{"rendered":"TCR-based therapy directed against kallikrein-related peptidase 4 is safe and effective against prostate cancer"},"content":{"rendered":"<div>\n<p><b>Cancer Immunol Res<\/b>. 2025 May 19. doi: 10.1158\/2326-6066.CIR-24-0119. Online ahead of print.<\/p>\n<p><b>ABSTRACT<\/b><\/p>\n<p>The efficacy of most immunotherapies for prostate cancer is limited by poor tumor immunogenicity, evidenced by minimal T-cell infiltration. Treatment with T cells engineered to express T-cell receptors (TCR) targeting prostate-specific antigens offers a potential solution by bypassing endogenous T-cell repertoire limitations. Through differential gene expression analysis, we have identified kallikrein-related peptidases 2, 3 and 4 (KLK2, KLK3, KLK4) and homeobox B13 (HOXB13) as strictly prostate lineage-specific genes with high expression in prostate cancer and no expression in healthy tissues of risk. Naturally processed peptides derived from these antigens were identified, enabling T-cell enrichment using peptide-MHC multimers. High-avidity T cells targeting these antigens were isolated from allogeneic HLA-mismatched donors. After screening for on-target tumor specificity and absence of off-target reactivity, TCRs recognizing KLK4 in HLA-A*02:01 and KLK3 in HLA-B*35:01 were sequenced and further tested. TCRs were expressed in T cells through TCR gene transfer and TCRs with best performance were selected. Using combinatorial peptide library scanning, the cross-reactive potential of the KLK4-A2 and KLK3-B35 TCRs was analyzed. The KLK3-B35 TCR exhibited cross-reactivity against two additional peptides derived from LOXHD1 and CDH23, with broad tissue-expression, and was therefore excluded. The KLK4-A2 TCR was highly specific for the KLK4 peptide. Further testing confirmed effective cytotoxic killing potential of KLK4-A2 TCR in vitro and in vivo, underscoring its therapeutic potential. These findings highlight the promise of the KLK4-A2 TCR for prostate cancer immunotherapy and demonstrate that prostate-specific antigens can be effectively targeted using TCR-gene transfer strategies.<\/p>\n<p>PMID:<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/40387827\/?utm_source=WordPress&amp;utm_medium=rss&amp;utm_content=101614637&amp;ff=20250519124717&amp;v=2.18.0.post9+e462414\">40387827<\/a> | DOI:<a href=\"https:\/\/doi.org\/10.1158\/2326-6066.CIR-24-0119\">10.1158\/2326-6066.CIR-24-0119<\/a><\/p>\n<\/div>","protected":false},"excerpt":{"rendered":"<p>Cancer Immunol Res. 2025 May 19. doi: 10.1158\/2326-6066.CIR-24-0119. Online ahead of print. ABSTRACT The efficacy of most immunotherapies for prostate cancer is limited by poor tumor immunogenicity, evidenced by minimal T-cell infiltration. Treatment with T cells engineered to express T-cell receptors (TCR) targeting prostate-specific antigens offers a potential solution by bypassing endogenous T-cell repertoire limitations. &#8230; <a title=\"TCR-based therapy directed against kallikrein-related peptidase 4 is safe and effective against prostate cancer\" class=\"read-more\" href=\"https:\/\/inmuno.es\/index.php\/2025\/05\/19\/tcr-based-therapy-directed-against-kallikrein-related-peptidase-4-is-safe-and-effective-against-prostate-cancer\/\" aria-label=\"Read more about TCR-based therapy directed against kallikrein-related peptidase 4 is safe and effective against prostate cancer\">Read more<\/a><\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[55,42],"tags":[],"class_list":["post-32914","post","type-post","status-publish","format-standard","hentry","category-cancer-immunology-reserch","category-publicaciones"],"_links":{"self":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/32914","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/comments?post=32914"}],"version-history":[{"count":0,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/32914\/revisions"}],"wp:attachment":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/media?parent=32914"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/categories?post=32914"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/tags?post=32914"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}