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Harold and Leila Y. Mathers Foundation","doi-asserted-by":"publisher","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"10.13039\/100011671","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Immunother Cancer"],"accepted":{"date-parts":[[2026,1,25]]},"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Colorectal cancer (CRC) is a leading cause of cancer-related death and remains a significant global health challenge. Cancer vaccines have emerged as a promising immunotherapy for long-term tumor control. While\n                      <jats:italic>Listeria monocytogenes<\/jats:italic>\n                      (\n                      <jats:italic>Lm<\/jats:italic>\n                      )-based intravenous vaccines can generate tumor-reactive CD8 T cells, clinical trial success has been limited. Here, we sought to determine whether\n                      <jats:italic>in vivo<\/jats:italic>\n                      targeting of gastrointestinal tissues with foodborne delivery of\n                      <jats:italic>Lm<\/jats:italic>\n                      -based cancer vaccines controlled tumor growth in murine models of CRC.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      The ActA and InlB virulence genes were deleted from a mouse-adapted\n                      <jats:italic>Lm<\/jats:italic>\n                      strain expressing ovalbumin and containing an internalin A mutation (InlA\n                      <jats:sup>M<\/jats:sup>\n                      <jats:italic>Lm<\/jats:italic>\n                      -ova) that allows epithelial cell invasion of mice to generate an oral vaccine administered via consumption of inoculated bread. Immunogenicity and safety were tested in C57Bl\/6 mice. Vaccine efficacy was evaluated with CRC tumors delivered by colonoscopy-guided orthotopic transplantation into the colon submucosa. Microsatellite instability high MC38 cell line expressing ovalbumin or genetically engineered microsatellite stable AKPS (\n                      <jats:italic>Apc<\/jats:italic>\n                      <jats:sup>KO<\/jats:sup>\n                      <jats:italic>Kras<\/jats:italic>\n                      <jats:sup>G12D<\/jats:sup>\n                      <jats:italic>Trp53<\/jats:italic>\n                      <jats:sup>KO<\/jats:sup>\n                      <jats:italic>Smad4<\/jats:italic>\n                      <jats:sup>KO<\/jats:sup>\n                      ) organoids expressing low levels of ovalbumin (lo\n                      <jats:sup>SIIN<\/jats:sup>\n                      ) were used. Vaccines were tested in prophylactic and therapeutic settings and in the context of immune checkpoint inhibitors (ICI).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Oral immunization induced a robust CD8 T cell response that was similar in magnitude and phenotype to the fully virulent\n                      <jats:italic>Lm<\/jats:italic>\n                      . Immunized mice did not lose weight, and\n                      <jats:italic>Lm<\/jats:italic>\n                      was contained to intestinal tissues. Mice prophylactically immunized with the vaccine were protected from CRC tumors. Therapeutic immunization of mice bearing lo\n                      <jats:sup>SIIN<\/jats:sup>\n                      AKPS tumors revealed curtailed growth of the local tumor but did not improve survival. Immunization with anti-programmed cell death protein-1 and anti-cytotoxic T-lymphocyte-associated protein 4 controlled tumors when coupled with therapeutic immunization. Protection correlated with accumulation of ova-specific CD8 T cells within the tumor.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Oral\n                      <jats:italic>Lm<\/jats:italic>\n                      -based cancer vaccines targeting CRC elicit robust, widely disseminated, and persistent tumor-specific immune responses in mice. These vaccines limit CRC development when administered prophylactically and provide tumor control when administered therapeutically with ICI. Thus, oral delivery of\n                      <jats:italic>Lm<\/jats:italic>\n                      -based cancer vaccines coupled with ICI may provide improved control of CRC progression in clinical application.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/jitc-2025-011570","type":"journal-article","created":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T14:30:18Z","timestamp":1770301818000},"page":"e011570","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":1,"title":["Oral immunization with\n                    <i>Listeria monocytogenes<\/i>\n                    vaccine enhances immunotherapy for protective immunity in murine models of colorectal cancer"],"prefix":"10.1136","volume":"14","author":[{"given":"Xinyuan","family":"Lei","sequence":"first","affiliation":[{"name":"Microbiology and Immunology, Stony Brook University Renaissance School of Medicine, Stony Brook, New York, 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