Immuno-oncology technology最新文献

{"title":"Thromboembolism in patients with melanoma receiving immune checkpoint inhibitors: incidence and risk factors","authors":"D.C.H. van Dorst ,&nbsp;M.M. Hofman ,&nbsp;R.M. de Waal ,&nbsp;E. Oomen-de Hoop ,&nbsp;K. de Joode ,&nbsp;S. Bins ,&nbsp;S.L.W. Koolen ,&nbsp;A. Joosse ,&nbsp;J. Versmissen ,&nbsp;M.J.H.A. Kruip ,&nbsp;A.A.M. van der Veldt ,&nbsp;R.H.J. Mathijssen","doi":"10.1016/j.iotech.2025.101063","DOIUrl":"10.1016/j.iotech.2025.101063","url":null,"abstract":"<div><h3>Background</h3><div>Immune checkpoint inhibitors (ICIs) may increase the incidence of thromboembolisms (TEs). In patients with melanoma, the risk of TE and its association with the disease setting remains largely unknown. This study investigated the incidences of arterial thromboembolism (ATE) and venous thromboembolism (VTE) and associated risk factors in ICI-treated patients with melanoma in the advanced and adjuvant disease settings.</div></div><div><h3>Patients and methods</h3><div>ATE and VTE incidences were retrospectively collected from patients receiving ICI in the advanced (irresectable stage III/IV) or adjuvant (stage III/IV, after complete resection) disease setting until 2 years or after censoring. Associations between characteristics and ATE/VTE were analyzed using the Fine–Gray model, with all-cause death as competing risk.</div></div><div><h3>Results</h3><div>In the advanced disease cohort, 7 (2.2%) and 16 (5.1%) of 315 included patients developed ATE and VTE, respectively. In the adjuvant cohort, 3 (2.1%) and 2 (1.4%) of 143 included patients developed ATE and VTE, respectively. In the advanced cohort, ICI combination therapy was associated with VTE [standardized hazard ration (sHR) 4.42, 95% confidence interval (CI) 1.58-12.38, <em>P</em> = 0.005] and higher body mass index (BMI) with ATE (sHR 1.09 per point BMI increase, 95% CI 1.02-1.17, <em>P</em> = 0.017), with a trend toward VTE (sHR 1.06, 95% CI 1.00-1.13, <em>P</em> = 0.055). In the adjuvant cohort, VTE history was associated with increased combined TE (sHR 11.22, 95% CI 1.83-68.68, <em>P</em> = 0.009) and higher BMI with a trend toward increased TE (sHR 1.19, 95% CI 0.97-1.46, <em>P</em> = 0.091).</div></div><div><h3>Conclusions</h3><div>Both ATE and VTE incidences seem to be modest in patients with melanoma receiving ICI in both disease settings. Patients with higher BMI and who are prescribed ICI combination therapy might be at increased thrombotic risk.</div></div>","PeriodicalId":73352,"journal":{"name":"Immuno-oncology technology","volume":"27 ","pages":"Article 101063"},"PeriodicalIF":0.0,"publicationDate":"2025-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144597140","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Properties of CD8 T-cell-recognized neoantigens in different tumor types","authors":"S.L.C. Ketelaars ,&nbsp;M.M. van Buuren ,&nbsp;A. Gangaev ,&nbsp;N. van Rooij ,&nbsp;S. Patiwael ,&nbsp;K. Hoefakker ,&nbsp;L.F. Fanchi ,&nbsp;P. Baas ,&nbsp;M. van der Heijden ,&nbsp;M. Kok ,&nbsp;T.N. Schumacher ,&nbsp;P. Kvistborg ,&nbsp;J.B.A.G. Haanen","doi":"10.1016/j.iotech.2025.101062","DOIUrl":"10.1016/j.iotech.2025.101062","url":null,"abstract":"<div><h3>Background</h3><div>Neoantigen-based immunotherapies rely on computational tools predicting peptide immunogenicity based on properties such as its expression level, binding affinity to human leukocyte antigen (HLA), likelihood of proteasomal cleavage and dissimilarity from wild-type peptide. However, current datasets are scarce and limited to highly mutated tumor types such as melanoma and lung cancer, leaving uncertainty about the value of these properties in other tumor types.</div></div><div><h3>Materials and methods</h3><div>To investigate this, we retrospectively analyzed the properties of immunogenic neoantigens identified in CD8 T-cell recognition screens of predicted neoantigens in tumor-infiltrating lymphocytes (TILs) from 12 melanoma patients and peripheral blood mononuclear cells (PBMCs) from 14 patients with mesothelioma, triple-negative breast cancer or urothelial cancer. In both experimental settings, CD8 T-cell recognition was assessed using a combinatorial peptide-HLA (pHLA) multimer-based technology.</div></div><div><h3>Results</h3><div>CD8 T-cell responses were detected against in total 34 of the 8103 predicted neoantigens (0.4%). In both PBMCs and TILs, the eluted ligand (EL) score—the predicted likelihood of a pHLA being presented on the cell surface—was the strongest predictor of immunogenicity, followed by predicted HLA binding affinity. Moreover, in the TILs, the frequency of neoantigen-specific CD8 T cells was strongly correlated with these properties across the 12 patients.</div></div><div><h3>Conclusions</h3><div>These findings underscore the value of both EL score and HLA binding affinity as key predictors of neoantigen immunogenicity in different tumor types. Furthermore, we demonstrate for the first time an immunodominance hierarchy of neoantigen-specific CD8 T-cell responses across patients in <em>ex vivo</em> expanded TIL cultures.</div></div>","PeriodicalId":73352,"journal":{"name":"Immuno-oncology technology","volume":"27 ","pages":"Article 101062"},"PeriodicalIF":0.0,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144703360","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A phase II study of nivolumab, ipilimumab, and radiation in combination with influenza vaccine in patients with pancreatic cancer (INFLUENCE)","authors":"I.M. Chen ,&nbsp;S. Theile ,&nbsp;K. Madsen ,&nbsp;J.S. Johansen ,&nbsp;T. Lorentzen ,&nbsp;A. Toxværd ,&nbsp;E. Høgdall ,&nbsp;I.M. Svane ,&nbsp;D. Nielsen","doi":"10.1016/j.iotech.2025.101054","DOIUrl":"10.1016/j.iotech.2025.101054","url":null,"abstract":"<div><h3>Background</h3><div>Considering strong T-cell response from influenza vaccination, we aimed to evaluate ipilimumab, nivolumab, seasonal influenza vaccine, and stereotactic body radiotherapy (SBRT) treatment efficacy in heavily pretreated patients with refractory pancreatic cancer (PC).</div></div><div><h3>Materials and methods</h3><div>In a single-center, phase II study (NCT05116917), individuals diagnosed with PC with progressive disease (PD) after gemcitabine- or fluorouracil-containing regimens were enrolled. SBRT (15 Gy) was administered on day 1 of the first cycle. Ipilimumab (1 mg/kg) was administered every 6 weeks and was limited to a maximum of two infusions. Nivolumab (3 mg/kg) was administered every 2 weeks until either PD or unacceptable toxicity, or for a maximum duration of 1 year. The influenza vaccine was administered subcutaneously on the first day of the first cycle. The primary endpoint was objective response rate with a predefined threshold of 15%. Secondary endpoints were progression-free survival (PFS), overall survival (OS), disease control rate, and safety.</div></div><div><h3>Results</h3><div>Between 15 November 2021 and 23 May 2023, 19 patients were enrolled and treated. As of data cut-off on 11 November 2023, the median follow-up time was 2.2 months (interquartile range 1.7-4.4 months). No objective responses or stable disease was observed. The median PFS was 1.6 months [95% confidence interval (CI) 1.4-1.8 months], and the median OS was 2.2 months (95% CI 1.8-4.6 months). Treatment-related adverse events were reported in 13 patients (68%), with 3 (16%) experiencing grade 3 or higher events.</div></div><div><h3>Conclusion</h3><div>Combined ipilimumab, nivolumab, influenza vaccine, and SBRT in patients with PC was feasible but did not lead to objective responses, and thus did not satisfy the predefined criteria for expanding to complete accrual.</div></div>","PeriodicalId":73352,"journal":{"name":"Immuno-oncology technology","volume":"26 ","pages":"Article 101054"},"PeriodicalIF":0.0,"publicationDate":"2025-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143935770","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Overcoming antigen loss in CAR T therapy with Vγ9Vδ2 CAR T-cells","authors":"M. Velasco Santiago ,&nbsp;P. Aehnlich ,&nbsp;T.M. Hulen ,&nbsp;K.M. Jensen ,&nbsp;G. Holmen Olofsson ,&nbsp;Ö. Met ,&nbsp;P. thor Straten","doi":"10.1016/j.iotech.2025.101053","DOIUrl":"10.1016/j.iotech.2025.101053","url":null,"abstract":"<div><h3>Background</h3><div>Vγ9Vδ2 T-cells demonstrate potent antitumor activity <em>in vitro</em> but, despite successful safety studies, the clinical benefit of Vγ9Vδ2 in adoptive cell therapy has been limited. One approach to enhance the therapeutic potential of Vγ9Vδ2 T-cells while maintaining their safety profile is genetic engineering to express a chimeric antigen receptor (CAR). Vγ9Vδ2 CAR T-cells retain the ability to target tumor cells even after target antigen loss, a major cause of CAR treatment relapse.</div></div><div><h3>Methods</h3><div>Vγ9Vδ2 T-cells were expanded from peripheral blood mononuclear cells in the presence of high levels of interleukin 2 (IL-2) or IL-2 in combination with IL-15. Cells were then virally transduced with a CD19-directed CAR and underwent antigen-specific stimulation to enrich CAR-expressing cells.</div></div><div><h3>Results</h3><div>Vγ9Vδ2 CAR T-cells showed similar cytotoxic activity to conventional αβ-CAR T-cells against CD19-positive tumor cells. They demonstrated superior responses against CD19-negative tumor cells, however, particularly when IL-15 was included during expansion. This enhanced function was further confirmed in co-culture assays with mixed CD19-positive and CD19-negative tumor populations, simulating antigen loss.</div></div><div><h3>Conclusions</h3><div>Vγ9Vδ2 CAR T-cell therapy presents a promising strategy for B-cell malignancies, offering sustained antitumor activity even after antigen loss. This approach may help overcome a major limitation of conventional CAR T-cell therapy, potentially improving clinical outcomes.</div></div>","PeriodicalId":73352,"journal":{"name":"Immuno-oncology technology","volume":"26 ","pages":"Article 101053"},"PeriodicalIF":0.0,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143808797","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessment of CD73 activity in breast cancer-derived small extracellular vesicles: application to monitoring of patients’ responses to immunotherapy","authors":"T.L. Whiteside ,&nbsp;S. Sehra ,&nbsp;T. Chadderton ,&nbsp;M. Guha ,&nbsp;M.C. Stubbs ,&nbsp;C. Timmers ,&nbsp;E.K. Jackson","doi":"10.1016/j.iotech.2025.101052","DOIUrl":"10.1016/j.iotech.2025.101052","url":null,"abstract":"<div><h3>Background</h3><div>We previously discovered that small extracellular vesicles (sEV) isolated from melanoma cells produce immunosuppressive adenosine (ADO) via the ATP→ADP→AMP→ADO pathway and that CD73 is the ‘gateway’ ecto-nucleotidase used by melanoma sEV to generate ADO. Here we extend these findings to CD39(+)CD73(+) and CD39(+)CD73(−) sEV from breast cancer cells.</div></div><div><h3>Materials and methods</h3><div>sEV were isolated from supernatants of a triple-negative breast cancer cell line ± the genetic knockout of CD73. A newly developed high pressure liquid chromatography assay with fluorescence detection was used for assessment of N⁶-etheno-AMP conversion to N⁶-etheno-ADO by sEV. PSB12379 (selective CD73 inhibitor) and anti-CD73 antibodies were used to inhibit/neutralize CD73 activity in sEV.</div></div><div><h3>Results</h3><div>Untreated sEV isolated from CD39(+)CD73(+) breast cancer cells readily metabolized N⁶-etheno-AMP to N⁶-etheno-ADO, and this activity was abolished by PSB12379. sEV from CD39(+)CD73(−) breast cancer cells were unable to metabolize N⁶-etheno-AMP to N⁶-etheno-ADO. Effects of three different anti-CD73 antibodies on CD73 activity in sEV were examined. Only one antibody, the direct binding pocket inhibitor of CD73, but not antibodies that allosterically inhibit recombinant CD73, attenuated conversion of N⁶-etheno-AMP to N⁶-etheno-ADO by cancer-derived sEV.</div></div><div><h3>Conclusions</h3><div>In breast cancer-derived sEV, as in melanoma-derived sEV, CD73 is the gateway enzyme regulating ADO formation from upstream AMP. The quantitation in sEV of N⁶-etheno-AMP conversion to N⁶-etheno-ADO ± neutralizing anti-CD73 antibodies provides a measure of the ability of these antibodies to suppress ADO production and could potentially serve as a personalized predictor of CD73 activity in patients with cancer.</div></div>","PeriodicalId":73352,"journal":{"name":"Immuno-oncology technology","volume":"26 ","pages":"Article 101052"},"PeriodicalIF":0.0,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143881778","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Solid tumour cellular therapy — principles of toxicity management","authors":"M. Julve ,&nbsp;Y.N.S. Wong ,&nbsp;K.H.J. Lim ,&nbsp;A.J.S. Furness","doi":"10.1016/j.iotech.2024.100737","DOIUrl":"10.1016/j.iotech.2024.100737","url":null,"abstract":"<div><div>Following the Food and Drug Administration (FDA) approval of lifileucel and afami-cel for patients with advanced melanoma and synovial sarcoma, respectively, there is a need for improved understanding and guidance regarding the management of toxicity associated with adoptive cellular therapies (ACTs) for solid tumours. Further approvals are expected in coming years, with toxicity management representing a significant consideration for centres looking to implement such advanced therapy medicinal products. Importantly, first-generation tumour-infiltrating lymphocyte therapies are associated with unique toxicities compared with gene-modified T-cell therapies such as chimeric antigen receptor T-cell therapy (CAR T) and T-cell receptor-modified therapy (TCR T), presenting novel challenges for treating healthcare professionals. Extrapolating from experience with CAR T in the field of haemato-oncology, coupled with the historical use of high-dose interleukin-2 in solid tumour therapeutic regimens and more recently lifileucel and afami-cel, has led to the development of core principles for managing toxicity, which is discussed here. Looking to the future, a rapidly developing field with next-generation ACT products, a basic knowledge of such core principles will be an important foundation for healthcare professionals working in this space.</div></div>","PeriodicalId":73352,"journal":{"name":"Immuno-oncology technology","volume":"25 ","pages":"Article 100737"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143739140","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical usefulness of anti-α3Gal immunoglobulin E assays for cetuximab-mediated anaphylaxis in head and neck cancer","authors":"Y. Pointreau ,&nbsp;C. Freneaux ,&nbsp;T. Bejan-Angoulvant ,&nbsp;D. Ternant ,&nbsp;G. Calais ,&nbsp;H. Watier","doi":"10.1016/j.iotech.2025.101041","DOIUrl":"10.1016/j.iotech.2025.101041","url":null,"abstract":"<div><h3>Background</h3><div>Fatal anaphylactic reactions to cetuximab remain a clinical issue, although they are associated with preexisting immunoglobulin E (IgE) directed against the galactose-α1,3-galactose epitope (α3Gal). We aimed to compare the clinical usefulness of the two assays and determine the prevalence of preexisting anti-α3Gal IgE.</div></div><div><h3>Patients and methods</h3><div>An anti-α3Gal IgE assay was developed (70BP assay) and compared with a commercial assay [bovine thyroglobulin (bTG) assay]. Both assays were applied to two cohorts: 299 healthy blood donors and 41 patients with head and neck cancer treated with cetuximab, including four patients with a history of anaphylactic reaction (9.8%).</div></div><div><h3>Results</h3><div>The prevalence of anti-α3Gal IgE was 6% and 5% using 70BP and bTG assays, respectively, in healthy blood donors. Among the head and neck cancer patients, the four who had an anaphylactic reaction were included in the seven (17.1%) and six (14.6%) patients with a signal above the detection threshold using the 70BP and bTG assays, respectively. This resulted in a sensitivity and negative predictive value of 100% for both assays, with a specificity of 91.9% and 94.6%, respectively, and a positive predictive value of 57.1% and 66.6% for the 70BP and bTG assays, respectively. Using an optimized threshold in the bTG assay, the prevalence of anti-α3Gal IgE in blood donors decreased to 1.3%, and five patients (12.2%) were eventually considered positive, giving a specificity of 97.3% and a positive predictive value of 80%.</div></div><div><h3>Conclusion</h3><div>The predictive value of anti-α3Gal IgE using these two assays was excellent and useful in clinical practice.</div></div>","PeriodicalId":73352,"journal":{"name":"Immuno-oncology technology","volume":"25 ","pages":"Article 101041"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143510956","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The MELimmune score—prognostic factors for overall survival in advanced melanoma and anti-PD-1 monotherapy—a multicentre, retrospective cohort study","authors":"S. Lobo-Martins ,&nbsp;D. Martins-Branco ,&nbsp;P.M. Semedo ,&nbsp;C.M. Alvim ,&nbsp;A.M. Monteiro ,&nbsp;I. Vendrell ,&nbsp;E. Gouveia ,&nbsp;M.J. Passos ,&nbsp;L. Costa ,&nbsp;A. Mansinho ,&nbsp;R.T. de Sousa","doi":"10.1016/j.iotech.2025.101043","DOIUrl":"10.1016/j.iotech.2025.101043","url":null,"abstract":"<div><h3>Background</h3><div>Immunotherapy has revolutionized advanced melanoma treatment. Several prognostic factors have been studied to predict survival in this setting. We aimed to develop a prognostic score.</div></div><div><h3>Materials and methods</h3><div>A multicentre, retrospective cohort study was conducted including patients with advanced melanoma who started anti-programmed cell death protein 1 (PD-1) monotherapy between January 2016 and October 2019 with ≤2 prior treatment lines. The study endpoint was overall survival (OS). Univariate and multivariate Cox regression identified independent prognostic factors, with 95% confidence intervals (CIs). The predictive accuracy of the model was evaluated by the receiver operating characteristic (ROC) curve model.</div></div><div><h3>Results</h3><div>We identified 147 patients with a median follow-up of 28.9 months (95% CI 22.5-33.5 months). The median OS (mOS) for the whole cohort was 14.8 months (95% CI 10.8-18.7 months). Overall, 43 and 104 patients were treated with nivolumab and pembrolizumab, respectively. We identified four prognostic factors at baseline: ≥3 metastatic sites [hazard ratio (HR) 1.90, 95% CI 1.21-2.97], performance status by Eastern Cooperative Oncology Group ≥1 (HR 2.02, 95% CI 1.28-3.18), lymphopenia (HR 2.85, 95% CI 1.54-5.27) or increased lactate dehydrogenase (HR 2.08, 95% CI 1.19-3.63). The MELimmune score grouped patients into three risk categories: favourable prognosis (no risk factors; <em>n</em> = 34), intermediate prognosis (one risk factor; <em>n</em> = 65) and poor prognosis (two or more risk factors; <em>n</em> = 48). The mOS was 43.4 (95% CI 32.1-54.7), 14.4 (95% CI 6.8-22.0) and 6.5 (95% CI 3.6-9.4) months for favourable, intermediate and poor prognosis groups, respectively (<em>P</em> &lt; 0.001). The area under the ROC curve was 0.74 (95% CI 0.66-0.82).</div></div><div><h3>Conclusion</h3><div>Using easily accessible variables from daily practice, the MELimmune prognostic score for patients with advanced melanoma treated with anti-PD-1 monotherapy holds potential to be used in clinical practice and prospectively validated in clinical trials.</div></div>","PeriodicalId":73352,"journal":{"name":"Immuno-oncology technology","volume":"25 ","pages":"Article 101043"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143509048","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Challenges and opportunities of predicting overall survival benefit from improvements to recurrence-free survival in stage II/III melanoma: a correlation meta-analysis","authors":"L. Leung ,&nbsp;J.M. Kirkwood ,&nbsp;S. Srinivasan ,&nbsp;M. Dyer ,&nbsp;A. Qian ,&nbsp;M.-M. Pourrahmat ,&nbsp;E. Kasireddy ,&nbsp;J.R. May ,&nbsp;A. Moshyk ,&nbsp;M. Kurt","doi":"10.1016/j.iotech.2025.101042","DOIUrl":"10.1016/j.iotech.2025.101042","url":null,"abstract":"<div><h3>Background</h3><div>We evaluated the association between treatment effects on recurrence-free survival (RFS) and overall survival (OS) in randomized controlled trials (RCTs) studying resected stage II/III melanoma.</div></div><div><h3>Methods</h3><div>Hazard ratios (HRs) of RFS and OS were obtained from a literature review. Bivariate random-effects meta-analysis (BRMA) and weighted linear regression (WLR) models estimated correlations [95% confidence interval (CI)] between HR_RFS and HR_OS. Slopes and intercepts of surrogacy equations were estimated. Surrogate threshold effect was derived from WLR for various sample sizes. Validity and predictive performance of WLR were assessed using leave-one-out cross-validation. Sensitivity analyses evaluated impact of RCTs violating proportional hazards assumption, publication year, treatments’ mechanism of action, and cancer stage.</div></div><div><h3>Results</h3><div>Across 30 RCTs, treatments included interferon-α (<em>n</em> = 17), other immunotherapy-containing regimens (<em>n</em> = 10), immune checkpoint inhibitors (<em>n</em> = 3), and targeted therapies (<em>n</em> = 2). BRMA (0.68, 95% CI 0.45-0.82) and WLR (0.71, 95% CI 0.42-0.87) estimated moderate correlation between HR_RFS and HR_OS. Surrogate threshold effect was 0.66/0.68 for studies with 800/1000 patients. Slope coefficients were statistically significant in both models (95% CI 0.09-0.61 BRMA; 95% CI 0.41-0.92 WLR). The 95% prediction intervals around the HR_OS predicted by WLR accurately contained 29/31 (93.5%) of observed HR_OS. Across sensitivity analyses correlations ranged between 0.69 and 0.84 (BRMA) and 0.55 and 0.77 (WLR).</div></div><div><h3>Conclusions</h3><div>Statistically meaningful correlation between HR_RFS and HR_OS can assist earlier predictions of OS benefit from improvements in RFS for RCTs in resected stage II/III melanoma and provide insights for the earlier evaluation of emerging therapies. Primary model predictions should be approached with caution as nearly half of the evidence base comprised interferon-α trials.</div></div>","PeriodicalId":73352,"journal":{"name":"Immuno-oncology technology","volume":"25 ","pages":"Article 101042"},"PeriodicalIF":0.0,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143479906","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Potentiating intratumoral therapy with immune checkpoint inhibitors: shifting the paradigm of multimodality therapeutics","authors":"B.E. Nelson ,&nbsp;A. Naing ,&nbsp;S. Fu ,&nbsp;R.A. Sheth ,&nbsp;R. Murthy ,&nbsp;S. Piha-Paul","doi":"10.1016/j.iotech.2024.101040","DOIUrl":"10.1016/j.iotech.2024.101040","url":null,"abstract":"<div><div>Immune checkpoint inhibitors (ICIs) have revolutionized oncology, yielding remarkable and durable responses in various cancers. However, a significant proportion of patients develop resistance to ICIs. The tumor microenvironment plays a critical role in immunotherapy resistance, characterized by immune cell composition, regulatory factors, and tumor mutational burden. Intratumoral immunotherapy, involving direct injection of immune-activating agents into tumors, holds promise for converting immunologically ‘cold’ tumors into responsive ‘hot’ tumors. This review explores the rationale for combining intratumoral therapies (ITs) with ICIs, highlighting their complementary mechanisms of action and clinical effects. Notable IT approaches include oncolytic viruses, toll-like receptor agonists, and stimulator of interferon gene agonists with ICIs. Overall, combining ITs with ICIs offers a rational strategy to potentiate antitumor immune response and overcome resistance. Further research is needed to optimize the combination strategies, identify biomarkers of response, and establish the safety and efficacy of these novel therapeutic approaches.</div></div>","PeriodicalId":73352,"journal":{"name":"Immuno-oncology technology","volume":"25 ","pages":"Article 101040"},"PeriodicalIF":0.0,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143155042","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}