Cancer Immunology, Immunotherapy最新文献

{"title":"Increased myositis and possible myocarditis in melanoma patients treated with immune checkpoint inhibitors in the COVID-19 era.","authors":"Allison L Gradone, Vincent T Ma, Alexi Vasbinder, Leslie A Fecher, Sarah Yentz, Salim S Hayek, Christopher D Lao","doi":"10.1007/s00262-024-03803-5","DOIUrl":"10.1007/s00262-024-03803-5","url":null,"abstract":"<p><strong>Background: </strong>Immune checkpoint inhibitor (ICI)-mediated myocarditis results in significant morbidity and mortality. At our institution, we noted an increased incidence of ICI-mediated myocarditis cases, leading to further investigation in our database of advanced melanoma patients treated with ICI therapy.</p><p><strong>Methods: </strong>A single-center, retrospective cohort analysis of patients with advanced melanoma identified cases of ICI-mediated myocarditis and myositis.</p><p><strong>Results: </strong>366 patients with advanced melanoma received a dose of ICI from September 2014 to October 2019. Of these patients, there were 0 cases of ICI-mediated myocarditis (0%, 95% CI 0%-1.0%) and 2 cases of ICI-mediated myositis (0.55%, 95% CI 0.07%-1.96%). From November 2019 to December 2021, an additional 246 patients with advanced melanoma were identified. Of these patients, 10 (4.1%, 95% CI 1.97%-7.35%) developed ICI-mediated myocarditis and 10 developed ICI-mediated myositis.</p><p><strong>Conclusion: </strong>Our study suggests an increase in prevalence of ICI-mediated muscle damage including myositis and myocarditis in the COVID-19 era. Differentiation of these patients and further risk stratification may allow for development of guidelines for nuanced management of this serious complication.</p>","PeriodicalId":9595,"journal":{"name":"Cancer Immunology, Immunotherapy","volume":"73 12","pages":"259"},"PeriodicalIF":5.4,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11456101/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142379131","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antitumor effects of intracranial injection of B7-H3-targeted Car-T and Car-Nk cells in a patient-derived glioblastoma xenograft model.","authors":"Tetsuro Tachi, Noriyuki Kijima, Hideki Kuroda, Syunya Ikeda, Koki Murakami, Tomoyoshi Nakagawa, Moto Yaga, Kanji Nakagawa, Reina Utsugi, Ryuichi Hirayama, Yoshiko Okita, Naoki Kagawa, Haruhiko Kishima, Chihaya Imai, Naoki Hosen","doi":"10.1007/s00262-024-03808-0","DOIUrl":"10.1007/s00262-024-03808-0","url":null,"abstract":"<p><strong>Background: </strong>Glioblastoma multiforme (GBM) is the most lethal primary brain tumor for which novel therapies are needed. Recently, chimeric antigen receptor (CAR) T cell therapy has been shown to be effective against GBM, but it is a personalized medicine and requires high cost and long time for the cell production. CAR-transduced natural killer (NK) cells can be used for \"off-the-shelf\" cellular immunotherapy because they do not induce graft-versus-host disease. Therefore, we aimed to analyze the anti-GBM effect of CAR-T or NK cells targeting B7-H3, which is known to be highly expressed in GBM.</p><p><strong>Methods: </strong>CAR-T cells targeting B7-H3 were generated using previously reported anti-B7-H3 scFv sequences. Cord blood (CB)-derived NK cells transduced with the B7-H3 CAR were also generated. Their anti-GBM effect was analyzed in vitro. The antitumor effect of intracranial injection of the B7-H3 CAR-T or NK cells was investigated in an in vivo xenograft model with patient-derived GBM cells.</p><p><strong>Results: </strong>Both B7-H3 CAR-T cells and CAR-NK cells exhibited marked cytotoxicity against patient-derived GBM cells in vitro. Furthermore, intracranial injection of CAR-T cells and CAR-NK cells targeting B7-H3 resulted in a significant antitumor effect against patient-derived GBM xenografts.</p><p><strong>Conclusion: </strong>Not only CAR-T cells but also CB-derived CAR-NK cells targeting B7-H3 may have the potential to eliminate GBM cells.</p>","PeriodicalId":9595,"journal":{"name":"Cancer Immunology, Immunotherapy","volume":"73 12","pages":"256"},"PeriodicalIF":5.4,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11456075/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142379129","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrative analyses of bulk and single-cell RNA-seq reveals the correlation between SPP1⁺ macrophages and resistance to neoadjuvant chemoimmunotherapy in esophageal squamous cell carcinoma.","authors":"Zhenyang Geng, Feng Li, Zhichang Yang, Bowen Li, Yifan Xu, Bin Wu, Yinliang Sheng, Ping Yuan, Lan Huang, Yu Qi","doi":"10.1007/s00262-024-03848-6","DOIUrl":"10.1007/s00262-024-03848-6","url":null,"abstract":"<p><p>Neoadjuvant chemoimmunotherapy (NACI) has significant implications for the treatment of esophageal cancer. However, its clinical efficacy varies considerably among patients, necessitating further investigation into the underlying mechanisms. The rapid advancement of single-cell RNA sequencing (scRNA-seq) technology facilitates the analysis of patient heterogeneity at the cellular level, particularly regarding treatment outcomes. In this study, we first analyzed scRNA-seq data of esophageal squamous cell carcinoma (ESCC) following NACI, obtained from the Gene Expression Omnibus (GEO) database. After performing dimensionality reduction, clustering, and annotation on the scRNA-seq data, we employed CellChat to investigate differences in cell-cell communication among samples from distinct efficacy groups. The results indicated that macrophages in the non-responder exhibited stronger cell communication intensity compared to those in responders, with SPP1 and GALECTIN signals showing the most significant differences between the two groups. This finding underscores the crucial role of macrophages in the efficacy of NACI. Subsequently, reclustering of macrophages revealed that Mac-SPP1 may be primarily responsible for treatment resistance, while Mac-C1QC appears to promote T cell activation. Finally, we conducted transcriptome sequencing on ESCC tissues obtained from 32 patients who underwent surgery following NACI. Utilizing CIBERSORT, CIBERSORTx, and WGCNA, we analyzed the heterogeneity of tumor microenvironment among different efficacy groups and validated the correlation between SPP1⁺ macrophages and resistance to NACI in ESCC using publicly available transcriptome sequencing datasets. These findings suggest that SPP1⁺ macrophages may represent a key factor contributing to resistance against NACI in ESCC.</p>","PeriodicalId":9595,"journal":{"name":"Cancer Immunology, Immunotherapy","volume":"73 12","pages":"257"},"PeriodicalIF":5.4,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11455823/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142379132","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to: Development of nomograms to predict therapeutic response and prognosis of non-small cell lung cancer patients treated with anti-PD-1 antibody.","authors":"Shijin Yuan, Yan Xia, Lihong Shen, Liuqing Ye, Lisha Li, Lifen Chen, Xinyou Xie, Haizhou Lou, Jun Zhang","doi":"10.1007/s00262-024-03812-4","DOIUrl":"10.1007/s00262-024-03812-4","url":null,"abstract":"","PeriodicalId":9595,"journal":{"name":"Cancer Immunology, Immunotherapy","volume":"73 12","pages":"258"},"PeriodicalIF":4.6,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11455839/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142379130","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhanced anti-tumor efficacy of electroporation (EP)-mediated DNA vaccine boosted by allogeneic lymphocytes in pre-established tumor models.","authors":"Sanyuan Shi, Luchen Zhang, Anjie Zheng, Fang Xie, Samuel Kesse, Yang Yang, Jinliang Peng, Yuhong Xu","doi":"10.1007/s00262-024-03838-8","DOIUrl":"10.1007/s00262-024-03838-8","url":null,"abstract":"<p><strong>Background: </strong>Tumor-reactive T cells play a crucial role in anti-tumor responses, but T cells induced by DNA vaccination are time-consuming processes and exhibit limited anti-tumor efficacy. Therefore, we evaluated the anti-tumor effectiveness of reactive T cells elicited by electroporation (EP)-mediated DNA vaccine targeting epidermal growth factor receptor variant III (pEGFRvIII plasmid), in conjunction with adoptive cell therapy (ACT), involving the transfer of lymphocytes from a pEGFRvIII EP-vaccinated healthy donor.</p><p><strong>Methods: </strong>The validation of the established pEGFRvIII plasmid and EGFRvIII-positive cell model was confirmed through immunofluorescence and western blot analysis. Flow cytometry and cytotoxicity assays were performed to evaluate the functionality of antigen-specific reactive T cells induced by EP-mediated pEGFRvIII vaccines, ACT, or their combination. The anti-tumor effectiveness of EP-mediated pEGFRvIII vaccines alone or combined with ACT was evaluated in the B16F10-EGFRvIII tumor model.</p><p><strong>Results: </strong>EP-mediated pEGFRvIII vaccines elicited serum antibodies and a robust cellular immune response in both healthy and tumor-bearing mice. However, this response only marginally inhibited early-stage tumor growth in established tumor models. EP-mediated pEGFRvIII vaccination followed by adoptive transfer of lymphocytes from vaccinated healthy donors led to notable anti-tumor efficacy, attributed to the synergistic action of antigen-specific CD4⁺ Th1 cells supplemented by ACT and antigen-specific CD8⁺ T cells elicited by the EP-mediated DNA vaccination.</p><p><strong>Conclusions: </strong>Our preclinical studies results demonstrate an enhanced anti-tumor efficacy of EP-mediated DNA vaccination boosted with adoptively transferred, vaccinated healthy donor-derived allogeneic lymphocytes.</p>","PeriodicalId":9595,"journal":{"name":"Cancer Immunology, Immunotherapy","volume":"73 12","pages":"248"},"PeriodicalIF":5.4,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11447239/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142364448","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the impact of durvalumab on biliary tract cancer: insights from real-world clinical data.","authors":"Patrick Reimann, Ilektra-Antonia Mavroeidi, Jonathan Burghofer, Hossein Taghizadeh, Gerald Webersinke, Stefan Kasper, Georg Schreil, Darius Morariu, Andreas Reichinger, Hideo Andreas Baba, Patrick Kirchweger, Martin Schuler, Angela Djanani, Gerald W Prager, Holger Rumpold, Magdalena Benda, Eva-Maria Schneider, Sylvia Mink, Thomas Winder, Bernhard Doleschal","doi":"10.1007/s00262-024-03842-y","DOIUrl":"10.1007/s00262-024-03842-y","url":null,"abstract":"<p><strong>Introduction: </strong>This study assesses the effectiveness of durvalumab with platinum and gemcitabine for biliary tract cancers (BTC). It aims to confirm the TOPAZ-1 trial results in a real-world context and explore the link between BTC molecular profiles and patient outcomes.</p><p><strong>Methods: </strong>A retrospective analysis was conducted on 102 BTC patients treated with durvalumab, platinum, and gemcitabine at five cancer centers in Austria and one in Germany from 2022 to 2024. Molecular profiling used targeted DNA and RNA assays. Clinical endpoints, including progression-free survival (PFS) and overall survival (OS), were assessed using log-rank tests and Cox regression, with correlations to second-line molecular-targeted therapies.</p><p><strong>Results: </strong>Among 102 patients, 60.8% had intrahepatic cholangiocarcinoma. The treatment achieved a disease control rate of 71.57% and an overall response rate of 35.11%. Median PFS was 6.51 months, and OS was 13.61 months. Patients under 65 had significantly better OS. Alterations in chromatin remodeling or homologous recombination repair genes were not predictive of survival benefit (HR: 0.45; p = 0.851 and HR: 1.63; p = 0.26, respectively). Patients with molecular-informed second-line therapy showed a trend toward survival benefit (HR: 0.23; p = 0.052).</p><p><strong>Conclusion: </strong>This study confirms the phase 3 trial results of durvalumab with platinum and gemcitabine, providing a substantial real-world dataset with detailed molecular characterization. No specific patient subgroup showed a markedly better response to durvalumab based on conventional NGS panels. Further research is needed to explore the link between immunotherapy responses and molecular subgroups.</p>","PeriodicalId":9595,"journal":{"name":"Cancer Immunology, Immunotherapy","volume":"73 12","pages":"251"},"PeriodicalIF":5.4,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11447177/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142364449","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dose-escalation, tolerability, and efficacy of intratumoral and subcutaneous injection of hemagglutinating virus of Japan envelope (HVJ-E) against chemotherapy-resistant malignant pleural mesothelioma: a clinical trial.","authors":"Kazuma Sakura, Muneyoshi Kuroyama, Yasushi Shintani, Soichiro Funaki, Shinji Atagi, Yoshihisa Kadota, Kozo Kuribayashi, Takashi Kijima, Takashi Nakano, Toshihiro Nakajima, Masao Sasai, Meinoshin Okumura, Yasufumi Kaneda","doi":"10.1007/s00262-024-03815-1","DOIUrl":"10.1007/s00262-024-03815-1","url":null,"abstract":"<p><p>The hemagglutinating virus of Japan envelope (HVJ-E) is an inactivated Sendai virus particle with antitumor effect and inducing antitumor immunity. However, its dosage and efficacy have not been verified. We conducted a phase I clinical study on chemotherapy-resistant malignant pleural mesothelioma (MPM) aiming to determine the recommended dosage for a phase II study through dose-limiting toxicity and evaluate HVJ-E's preliminary efficacy. HVJ-E was administered intratumorally and subcutaneously to the patients with chemotherapy-resistant MPM. While no serious adverse events occurred, known adverse events of HVJ-E were observed. In the preliminary antitumor efficacy using modified response evaluation criteria in solid tumors (RECIST) criteria, three low-dose patients exhibited progressive disease, while all high-dose patients achieved stable disease, yielding disease control rates (DCRs) of 0% and 100%, respectively. Furthermore, the dose-dependent effect of HVJ-E revealed on DCR modified by RECIST and the baseline changes in target lesion size (by CT and SUL-peak; p < 0.05). Comparing targeted lesions receiving intratumoral HVJ-E with non-injected ones, while no clear difference existed at the end of the study, follow-up cases suggested stronger antitumor effects with intratumoral administration. Our findings suggest that HVJ-E could be safely administered to patients with chemotherapy-resistant MPM at both study doses. HVJ-E exhibited some antitumor activity against chemotherapy-resistant MPM, and higher doses tended to have stronger antitumor effects than lower doses. Consequently, a phase II clinical trial with higher HVJ-E doses has been conducted for MPM treatment. Trial registration number: UMIN Clinical Trials Registry (#UMIN000019345).</p>","PeriodicalId":9595,"journal":{"name":"Cancer Immunology, Immunotherapy","volume":"73 12","pages":"243"},"PeriodicalIF":5.4,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11447170/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142364445","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"INTASYL self-delivering RNAi decreases TIGIT expression, enhancing NK cell cytotoxicity: a potential application to increase the efficacy of NK adoptive cell therapy against cancer.","authors":"Melissa Maxwell, Dingxue Yan, Brianna Rivest, Andrew Boone, James Cardia, Elfriede Noessner","doi":"10.1007/s00262-024-03835-x","DOIUrl":"10.1007/s00262-024-03835-x","url":null,"abstract":"<p><p>Natural killer (NK) cells are frontline defenders against cancer and are capable of recognizing and eliminating tumor cells without prior sensitization or antigen presentation. Due to their unique HLA mismatch tolerance, they are ideal for adoptive cell therapy (ACT) because of their ability to minimize graft-versus-host-disease risk. The therapeutic efficacy of NK cells is limited in part by inhibitory immune checkpoint receptors, which are upregulated upon interaction with cancer cells and the tumor microenvironment. Overexpression of inhibitory receptors reduces NK cell-mediated cytotoxicity by impairing the ability of NK cells to secrete effector cytokines and cytotoxic granules. T-cell immunoreceptor with immunoglobulin and ITIM domains (TIGIT), a well-known checkpoint receptor involved in T-cell exhaustion, has recently been implicated in the exhaustion of NK cells. Overcoming TIGIT-mediated inhibition of NK cells may allow for a more potent antitumor response following ACT. Here, we describe a novel approach to TIGIT inhibition using self-delivering RNAi compounds (INTASYL™) that incorporates the features of RNAi and antisense technology. INTASYL compounds demonstrate potent activity and stability, are rapidly and efficiently taken up by cells, and can be easily incorporated into cell product manufacturing. INTASYL PH-804, which targets TIGIT, suppresses TIGIT mRNA and protein expression in NK cells, resulting in increased cytotoxic capacity and enhanced tumor cell killing in vitro. Delivering PH-804 to NK cells before ACT has emerged as a promising strategy to counter TIGIT inhibition, thereby improving the antitumor response. This approach offers the potential for more potent off-the-shelf products for adoptive cell therapy, particularly for hematological malignancies.</p>","PeriodicalId":9595,"journal":{"name":"Cancer Immunology, Immunotherapy","volume":"73 12","pages":"239"},"PeriodicalIF":5.4,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11447204/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142364453","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multi-omics analysis and response prediction of PD-1 monoclonal antibody containing regimens in patients with relapsed/refractory diffuse large B-cell lymphoma.","authors":"Xinrui Chen, Yan Qin, Xuemin Xue, Zucheng Xie, Tongji Xie, Liling Huang, Haohua Zhu, Lina Gao, Jiangtao Li, Jianliang Yang, Lin Gui, Sheng Yang, Haizhu Chen, Xiaoli Feng, Yuankai Shi","doi":"10.1007/s00262-024-03840-0","DOIUrl":"10.1007/s00262-024-03840-0","url":null,"abstract":"<p><p>Patients with relapsed/refractory (r/r) diffuse large B-cell lymphoma (DLBCL) show varied responses to PD-1 monoclonal antibody (mAb) containing regimens. The mechanisms and predictive biomarkers for the efficacy of this regimen are unclear. This study retrospectively collected r/r DLBCL patients who received PD-1 mAb and rituximab regimens as salvage therapy. Clinical and genomic features were collected, and mechanisms were explored by multiplex immunofluorescence and digital spatial profiling. An artificial neural network (ANN) model was constructed to predict the response. Between October 16th, 2018 and May 4th, 2023, 50 r/r DLBCL patients were collected, 29 were response patients and 21 were non-response patients. CREBBP (p = 0.029) and TP53 (p = 0.015) alterations were statistically higher in non-response patients. Patients with PD-L1 CPS ≥ 5 were correlated with a longer overall survival (OS) than those with PD-L1 CPS < 5 (median OS: not reached vs. 9.7 months, hazard ratio [HR]: 3.8, 95% confidence interval [CI] 0.64-22.44, p = 0.016). Immune-related pathways were activated in response patients. The proportion and spatial organization of tumor-infiltrating immune cells affect the response. PD-L1 CPS level, age, and alterations of TP53, MYD88, CREBBP, EP300, GNA13 were used to build an ANN predictive model that showed high prediction efficiency (training set area under curve [AUC] of 0.97 and test set AUC of 0.94). The proportion and spatial distribution of tumor-infiltrating immune cells may be related to the function of immune-related pathways, thereby influencing the efficacy of PD-1 mAb containing regimens. The ANN predictive model showed potential value in predicting the responses of r/r DLBCL patients received PD-1 mAb and rituximab regimens.</p>","PeriodicalId":9595,"journal":{"name":"Cancer Immunology, Immunotherapy","volume":"73 12","pages":"250"},"PeriodicalIF":5.4,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11448501/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142364521","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapeutic antibodies in oncology: an immunopharmacological overview.","authors":"Karen Toledo-Stuardo, Carolina H Ribeiro, Fabiola González-Herrera, Douglas J Matthies, María Soledad Le Roy, Claudio Dietz-Vargas, Yesenia Latorre, Ivo Campos, Yuneisy Guerra, Samantha Tello, Valeria Vásquez-Sáez, Pedro Novoa, Nicolás Fehring, Mauricio González, Jose Rodríguez-Siza, Gonzalo Vásquez, Pamela Méndez, Claudia Altamirano, María Carmen Molina","doi":"10.1007/s00262-024-03814-2","DOIUrl":"10.1007/s00262-024-03814-2","url":null,"abstract":"<p><p>The biotechnological development of monoclonal antibodies and their immunotherapeutic use in oncology have grown exponentially in the last decade, becoming the first-line therapy for some types of cancer. Their mechanism of action is based on the ability to regulate the immune system or by interacting with targets that are either overexpressed in tumor cells, released into the extracellular milieu or involved in processes that favor tumor growth. In addition, the intrinsic characteristics of each subclass of antibodies provide specific effector functions against the tumor by activating antibody-dependent cellular cytotoxicity, complement-dependent cytotoxicity, and antibody-dependent cellular phagocytosis, among other mechanisms. The rational design and engineering of monoclonal antibodies have improved their pharmacokinetic and pharmacodynamic features, thus optimizing the therapeutic regimens administered to cancer patients and improving their clinical outcomes. The selection of the immunoglobulin G subclass, modifications to its crystallizable region (Fc), and conjugation of radioactive substances or antineoplastic drugs may all improve the antitumor effects of therapeutic antibodies. This review aims to provide insights into the immunological and pharmacological aspects of therapeutic antibodies used in oncology, with a rational approach at molecular modifications that can be introduced into these biological tools, improving their efficacy in the treatment of cancer.</p>","PeriodicalId":9595,"journal":{"name":"Cancer Immunology, Immunotherapy","volume":"73 12","pages":"242"},"PeriodicalIF":4.6,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11448508/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142364526","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}