Endpoint titers of plasma antibodies at week 12 amongst vaccine responders

Importance:Clonal hematopoiesis of indeterminate potential (CHIP) has been associated with increased risk of cardiovascular disease (CVD) events and mortality. However, there are no approved therapies for preventing or treating CHIP. Objective:To investigate whether low-dose aspirin might benefit older adults with CHIP for the primary prevention of CVD. Design, Setting, and Participants:This was a prespecified substudy of the Aspirin in Reducing Events in the Elderly (ASPREE) double-blind, randomized clinical trial of daily low-dose aspirin vs placebo evaluating disability-free survival, which took place at primary and community care facilities in the US and Australia. Enrollment was from March 2010 to December 2014, and the randomized trial ended in June 2017. Community-dwelling Australian adults aged 70 years and older without a diagnosed cardiovascular event, atrial fibrillation, a serious intercurrent illness likely to cause death within the next 5 years, anemia, or a current or recurrent condition with a high risk of bleeding were included in the original study. Of 19 114 in the original trial, 11 402 were included in the substudy, and 9434 were included in the analysis. Follow-up for this substudy went through June 2022, with data analysis in February 2025. In-trial median (IQR) follow-up time was 4.6 (3.5-5.6) years, and posttrial observational follow-up was 8.7 (7.5-10.1) years from randomization. Interventions:Participants were randomized to aspirin, 100 mg, daily or placebo. Main Outcomes and Measures:CHIP was measured in blood specimens collected at trial entry. Major adverse cardiovascular events (MACEs), including fatal and nonfatal ischemic stroke, nonfatal myocardial infarction and coronary heart disease death, and clinically significant bleeding were adjudicated by independent expert committees blinded to trial-group assignments. Results:A total of 9434 participants (median [IQR] age, 73.7 [71.6-77.1] years; 5067 [54%] female) provided a sample at baseline for analysis, 2124 of whom (23%) had CHIP at variant allele fraction (VAF) ≥2%, with 532 (5.6%) at ≥10% VAF. CHIP was not associated with increased risk of MACEs at 2% to 10% VAF (adjusted hazard ratio [aHR], 0.84, 95% CI, 0.68-1.03; P = .09) or ≥10% VAF (aHR, 0.80, 95% CI, 0.57-1.12; P = .19). However, CHIP was associated with increased risk of clinically significant bleeding (2%-10% VAF: aHR, 1.24; 95% CI 1.02-1.51; P = .03; ≥10% VAF: aHR, 1.21; 95% CI, 0.85-1.73; P = .28). There was no evidence of a differential effect of aspirin according to presence of CHIP on MACEs (without CHIP: HR, 0.91; 95% CI, 0.72-1.16; 2%-10% VAF: HR, 1.40; 95% CI, 0.77-2.53; ≥10% VAF: HR, 1.33; 95% CI, 0.52-3.37; heterogeneity P = .35) or clinically significant bleeding (without CHIP: HR, 1.64; 95% CI, 1.22-2.30; 2%-10% VAF: HR, 1.45; 95% CI, 0.82-2.57; ≥10% VAF: HR, 1.41; 95% CI, 0.49-4.07; heterogeneity P = .91). Conclusion and Relevance:In this secondary analysis of a randomized clinical trial of daily low-dose aspirin in healthy adults 70 years and older, CHIP was not associated with higher CVD risk. However, participants with CHIP had a greater risk of clinically significant bleeding. There was no evidence that participants with CHIP were more likely than those without CHIP to benefit or experience more harm from aspirin when used for primary prevention of CVD events. Trial Registration:ClinicalTrials.gov Identifier: NCT01038583.

ImportanceCancer mortality has decreased over time, but the contributions of different interventions across the cancer control continuum to averting cancer deaths have not been systematically evaluated across major cancer sites.ObjectiveTo quantify the contributions of prevention, screening (to remove precursors [interception] or early detection), and treatment to cumulative number of cancer deaths averted from 1975 to 2020 for breast, cervical, colorectal, lung, and prostate cancers.Design, Setting, and ParticipantsIn this model-based study using population-level cancer mortality data, outputs from published models developed by the Cancer Intervention and Surveillance Modeling Network were extended to quantify cancer deaths averted through 2020. Model inputs were based on national data on risk factors, cancer incidence, cancer survival, and mortality due to other causes, and dissemination and effects of prevention, screening (for interception and early detection), and treatment. Simulated or modeled data using parameters derived from multiple birth cohorts of the US population were used.InterventionsPrimary prevention via smoking reduction (lung), screening for interception (cervix and colorectal) or early detection (breast, cervix, colorectal, and prostate), and therapy (breast, colorectal, lung, and prostate).Main Outcomes and MeasuresThe estimated cumulative number of cancer deaths averted with interventions vs no advances.ResultsAn estimated 5.94 million cancer deaths were averted for breast, cervical, colorectal, lung, and prostate cancers combined. Cancer prevention and screening efforts averted 8 of 10 of these deaths (4.75 million averted deaths). The contribution of each intervention varied by cancer site. Screening accounted for 25% of breast cancer deaths averted. Averted cervical cancer deaths were nearly completely averted through screening and removal of cancer precursors as treatment advances were modest during the study period. Averted colorectal cancer deaths were averted because of screening and removal of precancerous polyps or early detection in 79% and treatment advances in 21%. Most lung cancer deaths were avoided by smoking reduction (98%) because screening uptake was low and treatment largely palliative before 2014. Screening contributed to 56% of averted prostate cancer deaths.Conclusions and RelevanceOver the past 45 years, cancer prevention and screening accounted for most cancer deaths averted for these causes; however, their contribution varied by cancer site according to these models using population-level cancer mortality data. Despite progress, efforts to reduce the US cancer burden will require increased dissemination of effective interventions and new technologies and discoveries.

Importance:The role of low-dose aspirin (LDA) in cancer prevention among older adults is unclear. Identifying individuals likely to experience benefit or harm is crucial for guiding personalized prevention strategies. Objective:To identify subgroups of the older population who may benefit most from LDA for cancer prevention by developing and validating an effect score model, including individual characteristics such as clonal hematopoiesis of indeterminate potential (CHIP) and other factors, to predict the individualized treatment effects (ITEs) of LDA in cancer incidence. Design, Setting, and Participants:This comparative effectiveness study is a nonprespecified secondary analysis of the Aspirin in Reducing Events in the Elderly (ASPREE) randomized clinical trial conducted between 2010 and 2014. Australian community-dwelling ASPREE participants (aged ≥70 years) provided biospecimen samples for CHIP testing. CHIP was measured in 18 genes using a targeted sequencing assay. Analyses were conducted between May 2023 and July 2025. Exposures:LDA (100 mg per day) or placebo. Main Outcomes and Measures:The primary outcome was overall cancer incidence at 5 years. Twelve candidate models for predicting ITEs were assessed; the final model was selected to maximize cancer risk reduction and internally validated using bootstrapping. Participants were grouped into treatment-favorable (ITE >0) and treatment-unfavorable (ITE <0) subgroups based on the final predictive model. Results:A total of 9350 participants were included in the analysis (median age, 73.7 [IQR, 71.6-77.1] years; 5021 females [53.7%]) to LDA (4667 [49.9%]) or placebo (4683 [50.1%]). The median follow-up was 4.5 (IQR, 3.3-5.5) years. Factors associated with LDA benefit included older age, nonsmoking status, CHIP with a variant allele frequency of 10% or greater, family history of cancer, and lower body mass index. CHIP was the strongest predictor of benefit. Personalized treatment based on the model improved 5-year absolute cancer risk reduction by a median of 2.3% (IQR, 0.7%-3.7%) compared with a treat-all approach (LDA to all participants). LDA was associated with lower cancer risk (hazard ratio [HR], 0.85 [95% CI, 0.72-1.00]) in the treatment-favorable subgroup and higher cancer risk (HR, 1.14 [95% CI, 0.95-1.38]) in the treatment-unfavorable subgroup (P = .02 for heterogeneity). Conclusions and Relevance:The findings of this study suggest significant heterogeneity in the effectiveness of LDA for cancer prevention among older adults, with CHIP identified as a key predictive factor. Further study is needed to fully understand the implications of these findings. Trial Registration:ClinicalTrials.gov Identifier: NCT01038583.

Background Information on Advanced Adenoma

MUC1 expression and immune infiltrate in baseline and recurrent adenoma pairs

TPS4212 Background: To prevent invasive esophageal adenocarcinoma (EAC), endoscopic eradication therapy (EET) is used to remove its precursor, Barrett’s esophagus (BE) with dysplasia. EET combines endoscopic removal of visible lesions with radiofrequency ablation (RFA) of surrounding BE to achieve complete remission of intestinal metaplasia (CRIM) and complete eradication of dysplasia (CED) to halt progression to cancer. Unfortunately, EET has metaplasia recurrence rates of 12.4%/year; thus, adjunctive cancer interception agents are needed to maintain the gains of EET. Data from pre-clinical studies and patient tissues demonstrate that the Hedgehog (Hh) pathway regulates esophageal stem cell activity and cell fate determination (squamous versus intestinal). Post-RFA reactivation of Hh signaling is hypothesized to drive BE recurrence; however, current FDA-approved Hh inhibitors are expensive and toxic. The antifungal itraconazole inhibits Hh signaling and has demonstrated antitumor activity in multiple cancers. In addition, it inhibits VEGFR and PI3K-AKT pathways, which are critical to BE development and neoplastic progression. Given its safety and affordability, itraconazole represents a promising strategy to reduce BE recurrence and EAC risk. Methods: This randomized, phase 2b, double-blind, placebo-controlled trial will evaluate itraconazole’s efficacy in accelerating BE eradication. Participants with high-risk BE, defined as BE ≥2 cm with low/high-grade dysplasia or intramucosal/T1 adenocarcinoma, undergoing ablation will be enrolled. Participants will be randomized 1:1 to receive 300 mg of oral itraconazole or placebo for two weeks before and four weeks after their first 2 sessions of EET. The primary endpoint is time to CRIM, a surrogate for long-term BE recurrence, measured in days. Secondary endpoints include time to CED, 12-month BE recurrence rates, safety, tolerability, and correlations between itraconazole levels and patient-reported outcomes. We will enroll 74 patients (37 per arm). We shall use a two-sided log rank test for right-censored time to event analysis to assess differences. The sample size calculation is based on anticipated surviving proportions at specific study times. We assume that the surviving non-CRIM proportions of patients at 3, 6, 9, and 12 months in the control arm to be 0.8, 0.5, 0.2, 0.1, respectively, and in the treatment arm to be 0.5, 0.2, 0.1, 0.05, respectively. To detect this effect size with 80% power at 5% level of significance, we need 30 evaluable participants in each group (with a plan to enroll 37 per arm to account for attrition). A Cox model will adjust for demographic and clinical variables. If successful, this trial could establish itraconazole as a novel adjunct to EET, reducing BE recurrence and lowering EAC risk. Clinical trial information: NCT06732388 .

Gastric cancer remains a major health challenge globally. In the United States, gastric cancer outcomes remain poor, with well-documented disparities in incidence and mortality. In 2024, the US National Cancer Institute convened a Think Tank on Advancing Gastric Cancer Prevention, with participation of over 200 global leaders from academia, clinical practice, and industry as well as patient advocates to exchange knowledge, lived experiences, and discuss future research opportunities. This commentary summarizes the Think Tank presentations and discussions of key existing evidence as well as challenges and opportunities for the prevention and control of this preventable disease. Primary prevention discussions focused on the use of the screen-and-treat strategy for Helicobacter pylori eradication. Secondary prevention discussions included endoscopic screening and surveillance of advanced gastric precancerous lesions. Primary conclusions for gastric cancer prevention and control included the need for (1) developing large-scale study resources that optimize the ability to conduct research with potential clinical translation applications; (2) strengthening and building community-public health-academic partnerships to enhance research; and (3) leveraging evidence-based strategies developed in high-risk East Asian countries to high-risk subgroups in low- and moderate-risk countries including the United States. There was overwhelming agreement that given the current state of gastric cancer incidence and survival in the United States, novel strategies to control the carcinogenic effects of H. pylori and to improve detection of precursors are the key to substantially reducing the burden of this disease.

Cancer interception represents a new approach, aimed at targeting precancerous lesions and therefore preventing cancer occurrence. Lynch syndrome (LS) is one of the most prevalent hereditary cancer syndromes, with an estimated prevalence of one in 300, and high-risk predisposition to several types of cancer, with up to 80% lifetime risk to develop CRC. LS is caused by germline mutations in one of the DNA mismatch repair (MMR) genes. Loss of MMR proteins causes an accumulation of mutations in the microsatellite sequences, known as Microsatellite instability (MSI), that can lead to shared frameshift mutations (FSP). Nous-209 is a neoantigen directed immunotherapy encoding 209 FSP shared across sporadic and hereditary MSI tumors and precancer lesions in clinical development for interception and treatment of MSI tumors (Leoni et al., 2020; NCT04041310). Here, we report the full set of safety and immunogenicity results of a Phase Ib/II study of Nous-209 monotherapy in LS carriers. NCT05078866 is a Phase Ib/II single-arm, open-label, trial of Nous-209 for cancer interception in LS carriers assessing as co-primary endpoints the safety and immunogenicity against the FSP neoantigens encoded by Nous-209. Nous-209 is administered intramuscularly: one prime with a Great Ape Adenovirus (GAd20-209-FSPs) on day 1, followed by a boost with a Modified Vaccinia Ankara (MVA-209-FSPs) at week 8. Immunogenicity was measured by ex-vivo IFN-γ ELISpot assay utilizing pre- and post-vaccination peripheral blood mononuclear cells (PMBCs) samples collected at different timepoints. The trial fully enrolled 45 LS carriers, all receiving GAd20-209-FSPs and MVA-209-FSPs. Most pts (21 of 45, 46.7%) harbored MSH2 pathogenic germline variants. 19 of 45 (42.2%) pts had a prior history of cancer. Treatment was safe and well tolerated with no treatment-related serious adverse events (AEs) and no unexpected reactogenicity. The most common AEs were injection site reactions (any grade: 84% post-prime, 73% post-boost; grade 3: 0%) and fatigue (any grade: 78% post-prime, 51% post-boost; grade 3: 4%). Neoantigen specific immune responses post Nous-209 were observed in 100% of evaluable participants (37/37), with induction of robust T cell immunity reaching a mean of T cell response at peak of ∼ 1100 IFN-γ spot forming cells (SFC) per million of PBMC, polyfunctional and long lasting CD8 and CD4 T cell responses broadly recognizing multiple FSPs. The use of peptide binding HLA predictions allowed the precise identification of several immunogenic FSPs, shown to be present in independent datasets of MSI premalignant lesions and cancers in LS carriers. The complete safety and immunogenicity results from this Phase Ib/II trial support the further development of Nous-209 monotherapy, highlighting its potential to efficiently stimulate the immune system and intercept cancer in LS carriers. Jason Willis, Anna Morena D'Alise, Michael J. Hall, Marcia Cruz-Correa, Gregory E. Idos, Selvi Thirumurthi, Veroushka Ballester, Guido Leoni, Irene Garzia, Laura Antonucci, Lorenzo De Marco, Elisa Micarelli, Sven Gogov, Wenli Dong, J. Jack Lee, Lana A. Vornik, Araceli Garcia-Gonzalez, Laura Reyes-Uribe, Ellen Richmond, Asad Umar, Powel H. Brown, Luz Maria Rodriguez, Elisa Scarselli, Eduardo Vilar. Nous-209 off-the-shelf neoantigen immunotherapy induces robust neoantigen T cell response with the potential to intercept cancer in Lynch syndrome carriers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 6427.

MDSC Values by Vaccine Immune Response vs. Non-Response

Improvements in cancer prevention and control are poised to be main contributors in reducing the burden of cancer in the United States. We quantify top opportunities to accelerate progress using projected life-years gained and deaths averted as measures. We project that over the next 25 years, realistic gains from tobacco control can contribute 0.4-17 million additional life-years gained per intervention and 8.4 million additional life-years gained from improving uptake of screening programs over the lifetime of 25 annual cohorts. Additional opportunities include addressing modifiable risk factors (excess weight, alcohol consumption), improving methods to prevent or treat oncogenic infections, and reducing cancer health disparities. Investment is needed in the pipeline of new preventive agents and technologies for early detection to continue progress. There is also a need for additional research to improve the access to and uptake of existing and emerging interventions for cancer prevention and control and to address health disparities. These gains are undeniably within our power to realize for the US population.

supplementary methods: trial administration

The risk of contracting mosquito-borne diseases upon being bitten by an infected mosquitoraises serious health concerns for both staff and students in educational settings. Consequentlya survey was conducted to identify various mosquito species and breeding sites within the oldcampus hostels of Bayero University, Kano, during January and February 2023. The surveyencompassed breeding sites such as stagnant pools of water, drainages, gutters, and discardedcontainers. Mosquito larvae were sampled using dippers and scoops, and their enumerationwas performed with a Pasteur pipette. Three genera were identified: Anopheles, Aedes, andCulex spp. A total of 1,115 larvae were sampled from six locations, per volume of water comprising three each from female hostels and three from male hostels respectively. Theprevalence of mosquitoes was higher in female hostels (785 larvae, 69.4%) compared to malehostels (370 larvae, 32.7%). In female hostels, Aedes sp. exhibited greater abundance (400, 50.9%) than Culex sp. (337, 42.9%), with Anopheles sp. being the least abundant (48, 6.11%).Conversely, in male hostels, Culex sp. dominated with 186 (50.2%), followed by Aedes sp. with 179 (48.3%), while Anopheles sp. was the least abundant with 5 (1.35%). Consequently, the mean abundance of mosquitoes between male and female hostels demonstrated a significantdifference. This study contributes valuable insights into the larval habitats of mosquitoes in thestudents’ hostels of Bayero University, Kano, specifically during the dry season. Factors suchas student activities, inadequate sensitization, and poor sanitation were identified as majorcontributors to the creation of breeding sites for mosquitoes in the hostels.

The study investigated the oviposition and egg viability effects of leaf extracts from Combretum micranthum, Xienmia americana, and Aloysia citrodora on female Anopheles gambiae mosquitoes. Leaves were sourced from Goron-maje Town, Dambatta LGA, Kano State, and extracts were prepared using ethanol, methanol, and ethyl-acetate. Bioassays were conducted at ambient temperature and relative humidity, testing oviposition activity and egg viability. Ethyl-acetate extracts, particularly from A. citrodora, significantly reduced oviposition compared to controls, with a 42.85% decrease. Ethanol extract of C. micranthum also showed reduced oviposition (8.84%). Significant differences were observed in the effects of different concentrations (ppm/mL) of plant extracts compared to controls. X. americana ethanol leaf extract at 20.0 ml concentration showed a 10% decrease in egg viability, while Combretum micranthum extracts at 20.0 ml and 30.0 ml concentrations showed 40.0% and 26.0% reductions in viability respectively. Aloysia citrodora methanol extracts exhibited a lower effect (48.0%) on viability compared to controls. X. americana ethanol leaf extract at 10% concentration significantly reduced hatching ability (26±06.21). Similarly, ethanol and ethyl-acetate extracts of C. micranthum and A. citrodora at 20.0 ml and 30.0 ml concentrations showed decreased hatching abilities compared to controls. The study suggests that ethanol and ethyl-acetate extracts of X. americana, C. micranthum, and A. citrodora could be effective and safer methods for mosquito control.

BACKGROUND AND AIMS: Effective approaches for prevention of hepatocellular carcinoma (HCC) will have a significant impact on HCC-related mortality. There are strong preclinical data and rationale to support targeting epidermal growth factor receptor (EGFR) for HCC chemoprevention. Small molecule inhibitors of EGFR have been Food and Drug Administration-approved for cancer therapy, which provides an opportunity to repurpose one of these drugs for chemoprevention of HCC. Unfortunately, the frequency of side effects associated with administration of these drugs at oncology doses renders them ineffective for chemoprevention. This clinical trial assesses whether lower doses of one of these inhibitors, erlotinib, still engages EGFR in the liver to block signaling (eg, EGFR phosphorylation). The objective of this clinical trial was determination of a safe and minimum effective dose of erlorinib for which >= 50% reduction phospho-EGFR immunohistochemical staining in the liver was observed. METHODS: Forty six participants were preregistered and 25 participants were registered in this multicenter trial. By dose de-escalation trial design, cohorts of participants received a 7-day course of erlotinib 75 mg/day, 50 mg/day or 25 mg/day with liver tissue acquisition prior to and after erlotinib. RESULTS: A >= 50% reduction phospho-EGFR immunohistochemical staining in the liver was observed in a minimum of 40% of participants (predetermined threshhold) at each of the dose levels. Erlotinib was very well tolerated with few side effects observed, particularly at the dose of 25 mg/day. Favorable modulation of the Prognostic Liver Signature was observed in participants who received erlotinib. CONCLUSION: These data support the selection of erlotinib doses as low as 25 mg/day of for a longer intervention to assess for evidence of efficacy as an HCC chemoprevention drug (ClinicalTrials.gov NCT02273362).

BACKGROUND:Cancer survivors can be at risk of cardiovascular disease (CVD) because of either their malignancy or its treatment. Although studies linking cancer and CVD exist, few examine risk in older adults, the impact of cancer treatment, or the effect of aspirin on reducing risk in this cohort. METHODS:The authors conducted a secondary analysis of the Aspirin in Reducing Events in the Elderly (ASPREE) trial to investigate the impact of cancer and cancer treatment on a composite CVD end point comprising hospitalization for heart failure (HHF), myocardial infarction (MI), and stroke. RESULTS:Of 15,454 Australian and US ASPREE participants, 1392 had an incident cancer diagnosis. Rates of CVD were greater in the cancer risk-set compared to the cancer-free risk-set (20.8 vs. 10.3 events per 1000 person-years; incidence rate ratio, 2.03; 95% confidence interval, 1.51-2.66), with increased incidence seen across MI, HHF, overall stroke, and ischemic stroke. Increased incidence remained after adjustment for clinically significant risk factors for CVD. Incidence was greatest in metastatic, hematological, and lung cancer. Chemotherapy was associated with increased risk of CVD. Similar rates of CVD were seen across aspirin and placebo groups. CONCLUSIONS:Incidence of CVD, including MI, HHF, and ischemic stroke, was increased in older adults with cancer. Aspirin did not impact CVD incidence. Risk may be higher in those with metastatic, hematological, and lung cancer, and following chemotherapy.

SUMMARY:Cancer prevention is central to efforts to control the burden of cancer. We propose a new terminology framework to help guide these efforts and promote a key equity principle: "equal care for equal risk."

Background Microsatellite instability (MSI) tumors are characterized by defects in the DNA mismatch repair (MMR) genes that lead to the accumulation of mutations within microsatellite (MS) loci. Indels in MS regions of coding genes can result in the synthesis of shared frameshift peptide (FSP) neoantigens, expected to be immunogenic and safe. MSI tumors develop sporadically or secondary to hereditary predisposition as part of Lynch Syndrome (LS), one of the most common hereditary colorectal cancers. Nous-209 is a genetic vaccine encoding 209 neoantigens shared across sporadic and hereditary MSI tumors developed for interception and treatment of MSI tumors.1 A phase I trial (NCT04041310) combining the Nous-209 vaccine with pembrolizumab anti-PD-1 antibody has been recently completed in metastatic colorectal, gastric and gastro-esophageal cancer patients showing excellent safety, immunogenicity, and promising signs of clinical efficacy.2 3 Here, we report the safety and immunogenicity of Nous-209 from the Phase Ib/II trial in LS carriers for the first 10 subjects. Methods NCT05078866 is a Phase Ib/II single-arm, open-label, clinical trial testing Nous-209 monotherapy for immune-interception in LS carriers. Safety and immunogenicity are the co-primary objectives. Nous-209 is administered intramuscularly: one prime with a Great Ape Adenovirus (GAd20-209-FSPs) on day 1, and boost with a Modified Vaccinia Ankara (MVA-209-FSPs) at week 8. Blood samples are collected for biomarker assays (Baseline, weeks 3, 8, 9, 24, and 52). Immunogenicity is evaluated on PBMC before and after vaccination by ex-vivo IFNγ ELISpot assay. Results On the data cutoff date (28 May 2023), 21 patients were enrolled in this NCI-sponsored study, 18 of those treated with both GAd and MVA. No dose limiting serious adverse events (SAEs) were observed (n=10), and the treatment appears safe and well tolerated. Immunogenicity was demonstrated in 100% of tested patients (n=10) with a mean peak response of ~700 IFN-γ SFCs/million PBMCs. No immune responses were detected at baseline prior vaccination in either previvors or survivors LS carriers. Nous-209-induced T cell responses were broad, recognizing different FSPs with induction of both CD4 and CD8 T cell responses. Deconvolution of T cell responses against predicted CD8 epitopes included in the FSPs pools showed multiple positive responses, confirming the optimal breadth of immune responses. Conclusions Nous-209 is safe, well tolerated, and elicits potent and broad immune response in both LS carriers previvors and survivors, supporting Nous-209 development as a compelling approach for LS cancer interception. References Leoni G, et al. A genetic vaccine encoding shared cancer neoantigens to treat tumors with microsatellite instability. Cancer Res. 2020;80(18):3972–3982. Fakih M, et al. First clinical and immunogenicity results including all subjects enrolled in a phase I study of Nous-209, an off-the-shelf immunotherapy, with pembrolizumab, for the treatment of tumors with a deficiency in mismatch repair/microsatellite instability (dMMR/MSI). Journal of Clinical Oncology 2022;40(16_suppl):2515–2515. D’Alise AM, et al. Adenoviral-based vaccine promotes neoantigen-specific CD8+ T cell stemness and tumor rejection. Science Translational Medicine 2022;14(657):eabo7604.