Source link <\/a><\/p>\n","protected":false},"excerpt":{"rendered":"Add topic to email alerts Receive an email when new articles are posted on Please provide your email address to receive an email when new articles are posted on . ” data-action=subscribe> Subscribe We were unable to process your request. Please try again later. If you continue to have this issue please contact customerservice@slackinc.com. Back to Healio Key takeaways: 18 of 20 individuals at high risk for pancreatic cancer achieved KRAS-specific T-cell responses after vaccination. No trial participants developed pancreatic cancer and five had resolution of pancreatic cysts. An investigational vaccine that targets common KRAS mutations induced durable immune responses among individuals at high risk for pancreatic cancer, results of a phase 1 clinical trial showed. Eighteen of 20 participants achieved KRAS-specific T-cell responses. Several individuals had either complete radiographic resolution or regression of pancreatic cysts, and none developed pancreatic cancer by data cutoff. Data derived from Haldar SD, et al. Cancer Discov. 2026;doi:10.1158\/2159-8290.CD-25-2245. The vaccine also appeared safe, according to researchers, with no grade 3 or higher adverse events reported. Elizabeth M. Jaffee \u201cDespite tremendous efforts, we have yet to develop a way to identify pancreatic cancer early enough to prevent most people from dying of it. An important question is: Can we intercept it before it develops?\u201d Elizabeth M. Jaffee, MD, FAACR, deputy director of Sidney Kimmel Cancer Center at Johns Hopkins and codirector of Skip Viragh Center for Pancreas Cancer at Johns Hopkins Medicine, told Healio. \u201cIf we can make more progress with screening modalities to better identify who is most at risk, hopefully we can get them a vaccine early and induce an immune response that prevents them from developing pancreatic cancer. I don\u2019t see that happening next year, but I\u2019m hopeful in the next 5 to 10 years that it will be a possibility.\u201d Seeking a \u2018huge advance\u2019 One in 10 people who develop pancreatic ductal adenocarcinoma (PDAC) have hereditary predisposition caused by pathogenic mutations in certain cancer susceptibility genes. Most PDAC cases are diagnosed at advanced stages due to a lack of early detection strategies and absence of early symptoms. The disease arises from precursor lesions, such as pancreatic intraepithelial neoplasia or intrapapillary mucinous neoplasms (IPMN). This process \u2014 which can take a decade or longer \u2014 creates \u201ca window of opportunity\u201d to intercept cancer development among high-risk individuals, according to study background. No such strategy currently exists. Patients found to have precursor lesions undergo surveillance and \u2014 if progression is detected \u2014 surgery is standard. However, precursor lesions often are microscopic and many cannot be detected by imaging. \u201cWe also have had instances where, during surveillance, it doesn\u2019t look like the primary lesion is progressing,\u201d Jaffee said. \u201cThen we determine the person has metastasis, even before we have detected a true pancreatic cancer within the pancreas itself.\u201d As many as 80% of patients with precursor lesions who undergo resection due to concern about transformation to cancer or detection of early malignancy develop recurrence. \u201cIt also is important to remember that this surgery is not harmless,\u201d Jaffee said. \u201cThere is significant morbidity. It takes over a year for a person\u2019s gastrointestinal tract to recover and make the enzymes needed to digest food, and patients often develop diabetes. It is not a simple operation so, if we could prevent this particular group of individuals from going to surgery, that would be a huge advance.\u201d Preventing \u2018chaos\u2019 Mutations in the KRAS gene are present in about 90% of pancreatic cancers, and they are a key driver in disease development and progression. In prior preclinical work, Jaffee and colleagues used a genetically engineered mouse model to evaluate whether a KRAS-targeted vaccine could prevent progression of early precancers. \u201cWe had hypothesized that if we could intercept them at the time of early KRAS activation, the immune system still may have the ability to react to this first change and prevent it from causing chaos that would induce more changes and ultimately lead to development of pancreatic cancer,\u201d Jaffee said. \u201cWe were shocked at how well it worked.\u201d The researchers then tested mKRAS-VAX \u2014 an off-the-shelf, synthetic long peptide vaccine that targets six KRAS mutations commonly found in PDAC and precancer lesions \u2014 in combination with dual checkpoint blockade for a dozen patients with early pancreatic cancer who had undergone surgical resection. Results published in Nature Communications showed median DFS of 6.3 months and median OS of 29.5 months from the time of first vaccine dose. Based on the evidence of immune response and vaccine safety, the investigators launched a phase 1 trial to evaluate the vaccine among 20 healthy individuals (median age, 66.5 years; range, 46-81) at high risk for PDAC based on familial and\/or germline predisposition. A majority of trial participants had at least one first-degree relative diagnosed with PDAC (85%) and harbored a germline mutation in a predisposition gene (60%). They all had radiographic evidence of a pancreatic abnormality, most often a small cyst indicative of IPMN. Participants received the vaccine via subcutaneous injections, with priming doses administered during weeks 1, 3 and 5, and a boost dose administered in week 13. Investigators collected blood samples at various time points and offered optional annual follow-up visits for long-term immune monitoring. Inducing \u2018memory response\u2019 Median follow-up reached 16.5 months. Results showed a median 18.2-fold increase (range, 1.8-167.1) in vaccinated individuals\u2019 mutant KRAS-specific T-cell responses, pooled as an average across all six KRAS antigens targeted. Researchers classified the 18 participants (90%) who achieved more than a 2.5-fold increase as immune responders. Longitudinal T-cell receptor sequencing showed responses remained detectable in the blood for as long as 2 years after vaccination. No vaccinated individuals developed pancreatic cancer and none had radiographically detected high-risk pancreatic lesions that warranted surgery. \u201cWhat makes the immune response so powerful is that it can react when the cancer is there \u2014 or even when a precancer is there \u2014 but also develops a memory response that acts quickly if that same precancer tries to come back again,\u201d Jaffee said. \u201cWe see this with<\/p>\n","protected":false},"author":1,"featured_media":3132,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[1],"tags":[],"class_list":["post-3131","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-uncategorized"],"_links":{"self":[{"href":"https:\/\/drsoniafawad.com\/index.php?rest_route=\/wp\/v2\/posts\/3131","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/drsoniafawad.com\/index.php?rest_route=\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/drsoniafawad.com\/index.php?rest_route=\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/drsoniafawad.com\/index.php?rest_route=\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/drsoniafawad.com\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=3131"}],"version-history":[{"count":0,"href":"https:\/\/drsoniafawad.com\/index.php?rest_route=\/wp\/v2\/posts\/3131\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/drsoniafawad.com\/index.php?rest_route=\/wp\/v2\/media\/3132"}],"wp:attachment":[{"href":"https:\/\/drsoniafawad.com\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=3131"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/drsoniafawad.com\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=3131"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/drsoniafawad.com\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=3131"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}
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