Immuno-oncology technology最新文献

{"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}

{"title":"An adjusted droplet digital PCR assay for quantification of vector copy number in CAR-T cell and TCR-T cell products","authors":"J. Ma ,&nbsp;S. Meyer ,&nbsp;J. Olweus ,&nbsp;C. Jin ,&nbsp;D. Yu","doi":"10.1016/j.iotech.2024.101031","DOIUrl":"10.1016/j.iotech.2024.101031","url":null,"abstract":"<div><h3>Background</h3><div>Genetically engineered T-cell therapy holds immense promise in cancer immunotherapy. These T-cell products are typically engineered by vectors that permanently integrate into the T-cell genome, thus raising concerns about potential risks of insertional mutagenesis. Therefore, it becomes imperative to assess the integrated vector copy number (VCN) as a critical safety parameter for gene-engineered cell products.</div></div><div><h3>Materials and methods</h3><div>In this study, we developed a robust assay for assessing the VCN of chimeric antigen receptor-T cell and T-cell receptor T-cell products, based on the droplet digital polymerase chain reaction (ddPCR) method. To provide accurate representation of the VCN in gene-engineered cells, we implemented a calculation that factors in the putative transduction efficiency based on Poisson distribution statistics. The adjusted VCN value (VCN_adj) was also compared with VCN value from sorted transgene-positive cell populations, to validate its accuracy.</div></div><div><h3>Results</h3><div>This assay consistently and accurately determines the average VCN for cell products. By comparing the VCN in sorted transgene-positive cell populations, we validated the refinement calculation provides a closer approximation to the actual VCN within transduced cells, offering a more realistic representation of the VCN for engineered cell products.</div></div><div><h3>Conclusion</h3><div>In summary, we present a reliable and robust ddPCR-based assay for quantification of VCN in gene-engineered cell products.</div></div>","PeriodicalId":73352,"journal":{"name":"Immuno-oncology technology","volume":"25 ","pages":"Article 101031"},"PeriodicalIF":0.0,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143155045","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":"Preclinical data and design of a phase I clinical trial of neoantigen-reactive TILs for advanced epithelial or ICB-resistant solid cancers","authors":"J. Palomero ,&nbsp;V. Galvao ,&nbsp;I. Creus ,&nbsp;J. Lostes ,&nbsp;M. Aylagas ,&nbsp;A. Marín-Bayo ,&nbsp;M. Rotxés ,&nbsp;M. Sanz ,&nbsp;M. Lozano-Rabella ,&nbsp;A. Garcia-Garijo ,&nbsp;A. Yuste-Estevanez ,&nbsp;D. Grases ,&nbsp;J. Díaz-Gómez ,&nbsp;J. González ,&nbsp;J.F. Navarro ,&nbsp;J.J. Gartner ,&nbsp;I. Braña ,&nbsp;X. Villalobos ,&nbsp;N. Bayó-Puxan ,&nbsp;J. Jiménez ,&nbsp;E. Garralda","doi":"10.1016/j.iotech.2024.101030","DOIUrl":"10.1016/j.iotech.2024.101030","url":null,"abstract":"<div><h3>Background</h3><div>Adoptive cell therapy (ACT) of <em>ex vivo</em> expanded tumor-infiltrating lymphocytes (TILs) can mediate objective tumor regression in 28%-49% of metastatic melanoma patients. However, the efficacy of TIL therapy in most epithelial cancers remains limited. We present the design of a phase I clinical study that aims to assess the safety and efficacy of NEXTGEN-TIL, a TIL product selected based on <em>ex vivo</em> neoantigen recognition, in patients with advanced epithelial tumors and immune checkpoint blockade (ICB)-resistant solid tumors.</div></div><div><h3>Materials and methods</h3><div>Pre-rapid expansion protocol (REP) TIL cultures expanded in high-dose interleukin 2 (HD-IL-2) from patients with metastatic solid tumors were screened for recognition of autologous tumor cell lines (TCLs) and/or neoantigens. Six good manufacturing practice (GMP)-grade validations of pre-REP TIL expansion were carried out and TIL cultures from these six intermediate products were selected to carry out the clinical-scale GMP validation of the REP.</div></div><div><h3>Results</h3><div>TILs expanded in 82% of patient-derived tumor biopsies across different cancer types and these frequently contained tumor- and neoantigen-reactive T cells. During GMP validations, a variable number of TIL cultures expanded, constituting the intermediate products (pre-REP). Three finished products were manufactured using a REP which reached cell doses ranging from 4.3e9 to 1.1e11 and met the established specifications. The NEXTGEN-TIL clinical trial entails a first expansion of TILs from tumor fragments in HD-IL-2 followed by TIL screening for neoantigen recognition and REP of selected neoantigen-reactive TIL cultures. Treatment involves a classical non-myeloablative lymphodepleting chemotherapy followed by NEXTGEN-TIL product administration together with HD-IL-2.</div></div><div><h3>Conclusions</h3><div>NEXTGEN-TIL exploits ex vivo expanded neoantigen-reactive TIL to potentially improve efficacy in patients with epithelial and ICB-resistant tumors, with a safety profile like traditional TILs.</div></div>","PeriodicalId":73352,"journal":{"name":"Immuno-oncology technology","volume":"25 ","pages":"Article 101030"},"PeriodicalIF":0.0,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143155987","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":"Title Page","authors":"","doi":"10.1016/S2590-0188(24)00315-0","DOIUrl":"10.1016/S2590-0188(24)00315-0","url":null,"abstract":"","PeriodicalId":73352,"journal":{"name":"Immuno-oncology technology","volume":"24 ","pages":"Article 101018"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143177785","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":"ESMO","authors":"","doi":"10.1016/S2590-0188(24)00316-2","DOIUrl":"10.1016/S2590-0188(24)00316-2","url":null,"abstract":"","PeriodicalId":73352,"journal":{"name":"Immuno-oncology technology","volume":"24 ","pages":"Article 101019"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143177787","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":"1O Exploration of gut microbiota biomarkers in treatment-naïve advanced NSCLC patients undergoing chemo-immunotherapy: Insights from the phase III trial, JCOG2007 (NIPPON)","authors":"T. Hakozaki ,&nbsp;K. Tanaka ,&nbsp;Y. Shiraishi ,&nbsp;Y. Sekino ,&nbsp;N. Mitome ,&nbsp;Y. Okuma ,&nbsp;T. Aiba ,&nbsp;T. Utsumi ,&nbsp;J. Tanizaki ,&nbsp;K. Azuma ,&nbsp;S. Hara ,&nbsp;R. Morita ,&nbsp;S. Niho ,&nbsp;T. Yokoyama ,&nbsp;R. Toyozawa ,&nbsp;H. Horinouchi ,&nbsp;I. Okamoto ,&nbsp;Y. Hosomi ,&nbsp;Y. Ohe","doi":"10.1016/j.iotech.2024.100885","DOIUrl":"10.1016/j.iotech.2024.100885","url":null,"abstract":"","PeriodicalId":73352,"journal":{"name":"Immuno-oncology technology","volume":"24 ","pages":"Article 100885"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143177797","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":"16P Immune checkpoint blockade and HLA-related epistasis in melanoma: Genetic determinants of response and toxicity","authors":"M. Little ,&nbsp;G. Milotay ,&nbsp;S. Mackay ,&nbsp;D. Muldoon ,&nbsp;A-A. Oluwafemi ,&nbsp;R. Watson ,&nbsp;O. Tong ,&nbsp;S. Sun ,&nbsp;C. Taylor ,&nbsp;M. Payne ,&nbsp;N.A. Coupe ,&nbsp;B. Shine ,&nbsp;B.P. Fairfax","doi":"10.1016/j.iotech.2024.100899","DOIUrl":"10.1016/j.iotech.2024.100899","url":null,"abstract":"","PeriodicalId":73352,"journal":{"name":"Immuno-oncology technology","volume":"24 ","pages":"Article 100899"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143139345","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":"59P Long term survival data from all recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) patients treated with MVX-ONCO-1 during open-labelled phase I and phase IIa clinical trials","authors":"N. Mach ,&nbsp;E. Fernandez ,&nbsp;R. Vernet ,&nbsp;M. Urwyler ,&nbsp;O. von Rohr ,&nbsp;E. Charrier ,&nbsp;M-C. Belkouch ,&nbsp;V. Saingier ,&nbsp;F. Courtout ,&nbsp;C. de Vito ,&nbsp;V. Ancrenaz ,&nbsp;N. Dulguerov ,&nbsp;W. Karenovics ,&nbsp;J. Grogg ,&nbsp;J. Renaux ,&nbsp;T. Brezina ,&nbsp;T. Rordorf ,&nbsp;M. Joerger ,&nbsp;O.A. Michielin ,&nbsp;J. Villard","doi":"10.1016/j.iotech.2024.100870","DOIUrl":"10.1016/j.iotech.2024.100870","url":null,"abstract":"","PeriodicalId":73352,"journal":{"name":"Immuno-oncology technology","volume":"24 ","pages":"Article 100870"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143128724","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}