journal
Journals Journal for Immunotherapy of C...

Journal for Immunotherapy of Cancer

https://read.qxmd.com/read/38642938/dysregulation-of-cd4-and-cd8-resident-memory-t-myeloid-and-stromal-cells-in-steroid-experienced-checkpoint-inhibitor-colitis
#1
JOURNAL ARTICLE
Jun Yan He, Yang-Joon Kim, Elvira Mennillo, Iulia Rusu, Jared Bain, Arjun A Rao, Christopher Andersen, Karen Law, Hai Yang, Jessica Tsui, Alan Shen, Brittany Davidson, Divyashree Kushnoor, Yimin Shi, Frances Fan, Alexander Cheung, Li Zhang, Lawrence Fong, Alexis J Combes, Angela O Pisco, Michael G Kattah, David Y Oh
BACKGROUND: Colitis caused by checkpoint inhibitors (CPI) is frequent and is treated with empiric steroids, but CPI colitis mechanisms in steroid-experienced or refractory disease are unclear. METHODS: Using colon biopsies and blood from predominantly steroid-experienced CPI colitis patients, we performed multiplexed single-cell transcriptomics and proteomics to nominate contributing populations. RESULTS: CPI colitis biopsies showed enrichment of CD4+ resident memory (RM) T cells in addition to CD8+ RM and cytotoxic CD8+ T cells...
April 19, 2024: Journal for Immunotherapy of Cancer
https://read.qxmd.com/read/38642937/phase-1a-dose-escalation-study-of-ivonescimab-ak112-smt112-an-anti-pd-1-vegf-a-bispecific-antibody-in-patients-with-advanced-solid-tumors
#2
JOURNAL ARTICLE
Sophia Frentzas, Anna Rachelle Austria Mislang, Charlotte Lemech, Adnan Nagrial, Craig Underhill, Wenjing Wang, Zhongmin Maxwell Wang, Baiyong Li, Yu Xia, Jermaine I G Coward
BACKGROUND: Studies showed that vascular endothelial growth factor (VEGF) inhibitors could improve therapeutic efficacy of PD-1/PD-L1 antibodies by transforming the immunosuppressive tumor microenvironment (TME) into an immunoresponsive TME. Ivonescimab is a first-in-class, humanized tetravalent bispecific antibody targeting PD-1 and VEGF-A simultaneously. Here, we report the first-in-human, phase 1a study of ivonescimab in patients with advanced solid tumors. METHODS: Patients with advanced solid tumors were treated with ivonescimab 0...
April 19, 2024: Journal for Immunotherapy of Cancer
https://read.qxmd.com/read/38641350/society-for-immunotherapy-of-cancer-sitc-recommendations-on-intratumoral-immunotherapy-clinical-trials-iict-from-premalignant-to-metastatic-disease
#3
JOURNAL ARTICLE
Jason J Luke, Diwakar Davar, Robert H Andtbacka, Nina Bhardwaj, Joshua D Brody, Jason Chesney, Robert Coffin, Thierry de Baere, Tanja D de Gruijl, Matthew Fury, Gregory Goldmacher, Kevin J Harrington, Howard Kaufman, Ciara M Kelly, Anuradha D Khilnani, Ke Liu, Sherene Loi, Georgina V Long, Ignacio Melero, Mark Middleton, Bart Neyns, David J Pinato, Rahul A Sheth, Stephen B Solomon, Philippe Szapary, Aurelien Marabelle
BACKGROUND: Intratumorally delivered immunotherapies have the potential to favorably alter the local tumor microenvironment and may stimulate systemic host immunity, offering an alternative or adjunct to other local and systemic treatments. Despite their potential, these therapies have had limited success in late-phase trials for advanced cancer resulting in few formal approvals. The Society for Immunotherapy of Cancer (SITC) convened a panel of experts to determine how to design clinical trials with the greatest chance of demonstrating the benefits of intratumoral immunotherapy for patients with cancers across all stages of pathogenesis...
April 18, 2024: Journal for Immunotherapy of Cancer
https://read.qxmd.com/read/38641349/association-of-metabolomics-with-pd-1-inhibitor-plus-chemotherapy-outcomes-in-patients-with-advanced-non-small-cell-lung-cancer
#4
JOURNAL ARTICLE
Liang Zheng, Fang Hu, Lin Huang, Jun Lu, Xiaohua Yang, Jianlin Xu, Shuyuan Wang, Yinchen Shen, Runbo Zhong, Tianqing Chu, Wei Zhang, Ying Li, Xiaoxuan Zheng, Baohui Han, Hua Zhong, Wei Nie, Xueyan Zhang
BACKGROUND: Combining immune checkpoint inhibitors (ICIs) with chemotherapy has become a standard treatment for patients with non-small cell lung cancer (NSCLC) lacking driver gene mutations. Reliable biomarkers are essential for predicting treatment outcomes. Emerging evidence from various cancers suggests that early assessment of serum metabolites could serve as valuable biomarkers for predicting outcomes. This study aims to identify metabolites linked to treatment outcomes in patients with advanced NSCLC undergoing first-line or second-line therapy with programmed cell death 1 (PD-1) inhibitors plus chemotherapy...
April 18, 2024: Journal for Immunotherapy of Cancer
https://read.qxmd.com/read/38631709/preclinical-evaluation-of-two-phylogenetically-distant-arenavirus-vectors-for-the-development-of-novel-immunotherapeutic-combination-strategies-for-cancer-treatment
#5
JOURNAL ARTICLE
Josipa Raguz, Catarina Pinto, Theresa Pölzlbauer, Mohamed Habbeddine, Sandra Rosskopf, Judith Strauß, Valentin Just, Sarah Schmidt, Katell Bidet Huang, Felix Stemeseder, Timo Schippers, Ethan Stewart, Jakub Jez, Pedro Berraondo, Klaus K Orlinger, Henning Lauterbach
BACKGROUND: Engineered arenavirus vectors have recently been developed to leverage the body's immune system in the fight against chronic viral infections and cancer. Vectors based on Pichinde virus (artPICV) and lymphocytic choriomeningitis virus (artLCMV) encoding a non-oncogenic fusion protein of human papillomavirus (HPV)16 E6 and E7 are currently being tested in patients with HPV16+ cancer, showing a favorable safety and tolerability profile and unprecedented expansion of tumor-specific CD8+ T cells...
April 17, 2024: Journal for Immunotherapy of Cancer
https://read.qxmd.com/read/38631707/germline-homozygosity-and-allelic-imbalance-of-hla-i-are-common-in-esophagogastric-adenocarcinoma-and-impair-the-repertoire-of-immunogenic-peptides
#6
JOURNAL ARTICLE
Maria Alejandra Garcia-Marquez, Martin Thelen, Eugen Bauer, Lukas Maas, Kerstin Wennhold, Jonas Lehmann, Diandra Keller, Miloš Nikolić, Julie George, Thomas Zander, Wolfgang Schröder, Philipp Müller, Ali M Yazbeck, Christiane Bruns, Roman Thomas, Birgit Gathof, Alexander Quaas, Martin Peifer, Axel M Hillmer, Michael von Bergwelt-Baildon, Hans Anton Schlößer
BACKGROUND: The individual HLA-I genotype is associated with cancer, autoimmune diseases and infections. This study elucidates the role of germline homozygosity or allelic imbalance of HLA-I loci in esophago-gastric adenocarcinoma (EGA) and determines the resulting repertoires of potentially immunogenic peptides. METHODS: HLA genotypes and sequences of either (1) 10 relevant tumor-associated antigens (TAAs) or (2) patient-specific mutation-associated neoantigens (MANAs) were used to predict good-affinity binders using an in silico approach for MHC-binding (www...
April 17, 2024: Journal for Immunotherapy of Cancer
https://read.qxmd.com/read/38631706/tumor-targeted-therapy-with-braf-inhibitor-recruits-activated-dendritic-cells-to-promote-tumor-immunity-in-melanoma
#7
JOURNAL ARTICLE
Florian Hornsteiner, Janine Vierthaler, Helen Strandt, Antonia Resag, Zhe Fu, Markus Ausserhofer, Christoph H Tripp, Sophie Dieckmann, Markus Kanduth, Kathryn Farrand, Sarah Bregar, Niloofar Nemati, Natascha Hermann-Kleiter, Athanasios Seretis, Sudhir Morla, David Mullins, Francesca Finotello, Zlatko Trajanoski, Guido Wollmann, Franca Ronchese, Marc Schmitz, Ian F Hermans, Patrizia Stoitzner
BACKGROUND: Tumor-targeted therapy causes impressive tumor regression, but the emergence of resistance limits long-term survival benefits in patients. Little information is available on the role of the myeloid cell network, especially dendritic cells (DC) during tumor-targeted therapy. METHODS: Here, we investigated therapy-mediated immunological alterations in the tumor microenvironment (TME) and tumor-draining lymph nodes (LN) in the D4M.3A preclinical melanoma mouse model (harboring the V-Raf murine sarcoma viral oncogene homolog B (BRAF)V600E mutation) by using high-dimensional multicolor flow cytometry in combination with multiplex immunohistochemistry...
April 17, 2024: Journal for Immunotherapy of Cancer
https://read.qxmd.com/read/38631714/efficacy-of-lcmv-based-cancer-immunotherapies-is-unleashed-by-intratumoral-injections-of-polyi-c
#8
JOURNAL ARTICLE
Celia Gomar, Claudia Augusta Di Trani, Angela Bella, Leire Arrizabalaga, Jose Gonzalez-Gomariz, Myriam Fernandez-Sendin, Maite Alvarez, Joan Salvador Russo-Cabrera, Nuria Ardaiz, Fernando Aranda, Timo Schippers, Marisol Quintero, Ignacio Melero, Klaus K Orlinger, Henning Lauterbach, Pedro Berraondo
BACKGROUND: Lymphocytic choriomeningitis virus (LCMV) belongs to the Arenavirus family known for inducing strong cytotoxic T-cell responses in both mice and humans. LCMV has been engineered for the development of cancer immunotherapies, currently undergoing evaluation in phase I/II clinical trials. Initial findings have demonstrated safety and an exceptional ability to activate and expand tumor-specific T lymphocytes. Combination strategies to maximize the antitumor effectiveness of LCMV-based immunotherapies are being explored...
April 16, 2024: Journal for Immunotherapy of Cancer
https://read.qxmd.com/read/38631713/immunotherapy-based-regimens-for-patients-with-egfr-mutated-non-small-cell-lung-cancer-who-progressed-on-egfr-tki-therapy
#9
JOURNAL ARTICLE
Bao-Dong Qin, Xiao-Dong Jiao, Ling-Yan Yuan, Ying Wu, Yan Ling, Yuan-Sheng Zang
No abstract text is available yet for this article.
April 16, 2024: Journal for Immunotherapy of Cancer
https://read.qxmd.com/read/38631712/combinational-therapy-of-car-t-cell-and-hdt-asct-demonstrates-impressive-clinical-efficacy-and-improved-car-t-cell-behavior-in-relapsed-refractory-large-b-cell-lymphoma
#10
JOURNAL ARTICLE
Wei Liu, Hesong Zou, Lianting Chen, Wenyang Huang, Rui Lv, Yan Xu, Huimin Liu, Yin Shi, Kefei Wang, Yi Wang, Wenjie Xiong, Shuhui Deng, Shuhua Yi, Weiwei Sui, Guangxin Peng, Yueshen Ma, Huijun Wang, Lulu Lv, Jianxiang Wang, Jun Wei, Lugui Qiu, Wenting Zheng, Dehui Zou
BACKGROUND: Approximately two-thirds of patients with relapsed or refractory large B-cell lymphoma (R/R LBCL) do not respond to or relapse after anti-CD19 chimeric antigen receptor T (CAR T)-cell therapy, leading to poor outcomes. Previous studies have suggested that intensified lymphodepletion and hematological stem cell infusion can promote adoptively transferred T-cell expansion, enhancing antitumor effects. Therefore, we conducted a phase I/II clinical trial in which CNCT19 (an anti-CD19 CAR T-cell) was administered after myeloablative high-dose chemotherapy and autologous stem cell transplantation (HDT/ASCT) in patients with R/R LBCL...
April 16, 2024: Journal for Immunotherapy of Cancer
https://read.qxmd.com/read/38631711/spatial-comparison-of-molecular-features-associated-with-resistance-to-pembrolizumab-in-bcg-unresponsive-bladder-cancer
#11
JOURNAL ARTICLE
Khyati Meghani, Noah Frydenlund, Yanni Yu, Bonnie Choy, Joshua J Meeks
Intravenous immune checkpoint inhibition achieves a 40% 3-month response in BCG-unresponsive non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ. Yet, only half of the early responders will continue to be disease-free by 12 months, and resistance mechanisms are poorly defined. We performed spatial profiling of BCG-unresponsive tumors from patients responsive or resistant to intravenous pembrolizumab treatment, analyzing samples both before initiating and 3 months post-intravenous pembrolizumab treatment...
April 16, 2024: Journal for Immunotherapy of Cancer
https://read.qxmd.com/read/38631710/b-cells-and-the-coordination-of-immune-checkpoint-inhibitor-response-in-patients-with-solid-tumors
#12
REVIEW
Ronan Flippot, Marcus Teixeira, Macarena Rey-Cardenas, Lucia Carril-Ajuria, Larissa Rainho, Natacha Naoun, Jean-Mehdi Jouniaux, Lisa Boselli, Marie Naigeon, Francois-Xavier Danlos, Bernard Escudier, Jean-Yves Scoazec, Lydie Cassard, Laurence Albiges, Nathalie Chaput
Immunotherapy profoundly changed the landscape of cancer therapy by providing long-lasting responses in subsets of patients and is now the standard of care in several solid tumor types. However, immunotherapy activity beyond conventional immune checkpoint inhibition is plateauing, and biomarkers are overall lacking to guide treatment selection. Most studies have focused on T cell engagement and response, but there is a growing evidence that B cells may be key players in the establishment of an organized immune response, notably through tertiary lymphoid structures...
April 16, 2024: Journal for Immunotherapy of Cancer
https://read.qxmd.com/read/38631708/preclinical-evaluation-and-first-in-dog-clinical-trials-of-pbmc-expanded-natural-killer-cells-for-adoptive-immunotherapy-in-dogs-with-cancer
#13
JOURNAL ARTICLE
Aryana M Razmara, Lauren E Farley, Rayna M Harris, Sean J Judge, Marshall Lammers, Khurshid R Iranpur, Eric G Johnson, Cordelia Dunai, William J Murphy, C Titus Brown, Robert B Rebhun, Michael S Kent, Robert J Canter
BACKGROUND: Natural killer (NK) cells are cytotoxic cells capable of recognizing heterogeneous cancer targets without prior sensitization, making them promising prospects for use in cellular immunotherapy. Companion dogs develop spontaneous cancers in the context of an intact immune system, representing a valid cancer immunotherapy model. Previously, CD5 depletion of peripheral blood mononuclear cells (PBMCs) was used in dogs to isolate a CD5dim -expressing NK subset prior to co-culture with an irradiated feeder line, but this can limit the yield of the final NK product...
April 16, 2024: Journal for Immunotherapy of Cancer
https://read.qxmd.com/read/38621815/tetracyclines-enhance-antitumor-t-cell-immunity-via-the-zap70-signaling-pathway
#14
JOURNAL ARTICLE
Mari Tone, Kota Iwahori, Michinari Hirata, Azumi Ueyama, Akiyoshi Tani, Jun-Ichi Haruta, Yoshito Takeda, Yasushi Shintani, Atsushi Kumanogoh, Hisashi Wada
BACKGROUND: Cancer immunotherapy including immune checkpoint inhibitors is only effective for a limited population of patients with cancer. Therefore, the development of novel cancer immunotherapy is anticipated. In preliminary studies, we demonstrated that tetracyclines enhanced T-cell responses. Therefore, we herein investigated the efficacy of tetracyclines on antitumor T-cell responses by human peripheral T cells, murine models, and the lung tumor tissues of patients with non-small cell lung cancer (NSCLC), with a focus on signaling pathways in T cells...
April 15, 2024: Journal for Immunotherapy of Cancer
https://read.qxmd.com/read/38609317/armored-tgf%C3%AE-riidn-ror1-car-t-cells-reject-solid-tumors-and-resist-suppression-by-constitutively-expressed-and-treatment-induced-tgf%C3%AE-1
#15
JOURNAL ARTICLE
Tri Minh Tran, Bal Krishna Chand Thakuri, Saule Nurmukhambetova, Jia-Jye Lee, Peirong Hu, Ngoc Q Tran, Brittany Steimle, Pradyot Dash, Dina Schneider
BACKGROUND: Chimeric antigen receptor (CAR) T-cell therapy target receptor tyrosine kinase-like orphan receptor 1 (ROR1) is broadly expressed in hematologic and solid tumors, however clinically-characterized ROR1-CAR T cells with single chain variable fragment (scFv)-R12 targeting domain failed to induce durable remissions, in part due to the immunosuppressive tumor microenvironment (TME). Herein, we describe the development of an improved ROR1-CAR with a novel, fully human scFv9 targeting domain, and augmented with TGFβRIIDN armor protective against a major TME factor, transforming growth factor beta (TGFβ)...
April 12, 2024: Journal for Immunotherapy of Cancer
https://read.qxmd.com/read/38609316/phase-1-study-combining-elotuzumab-with-autologous-stem-cell-transplant-and-lenalidomide-for-multiple-myeloma
#16
JOURNAL ARTICLE
David G Coffey, Keren Osman, Adolfo Aleman, Selma Bekri, Simone Kats, Amishi Dhadwal, Donna Catamero, Seunghee Kim-Schulze, Sacha Gnjatic, Ajai Chari, Samir Parekh, Sundar Jagannath, Hearn Jay Cho
BACKGROUND: Autologous stem cell transplantation (ASCT) after induction therapy improves disease-free survival for patients with multiple myeloma (MM). While the goal of ASCT is to render a minimal disease state, it is also associated with eradication of immunosuppressive cells, and we hypothesize that early introduction of immunotherapy post-ASCT may provide a window of opportunity to boost treatment efficacy. METHODS: We conducted a phase 1 clinical trial to investigate the application of autologous lymphocyte infusion and anti-SLAMF7 monoclonal antibody, elotuzumab, after ASCT in patients with newly diagnosed MM previously treated with induction therapy...
April 12, 2024: Journal for Immunotherapy of Cancer
https://read.qxmd.com/read/38609101/dual-molecule-targeting-hdac6-leads-to-intratumoral-cd4-cytotoxic-lymphocytes-recruitment-through-mhc-ii-upregulation-on-lung-cancer-cells
#17
JOURNAL ARTICLE
Sarah Ducellier, Mélanie Demeules, Boris Letribot, Massimiliano Gaetani, Chloé Michaudel, Harry Sokol, Abdallah Hamze, Mouad Alami, Mégane Nascimento, Sébastien Apcher
BACKGROUND: Despite the current therapeutic treatments including surgery, chemotherapy, radiotherapy and more recently immunotherapy, the mortality rate of lung cancer stays high. Regarding lung cancer, epigenetic modifications altering cell cycle, angiogenesis and programmed cancer cell death are therapeutic targets to combine with immunotherapy to improve treatment success. In a recent study, we uncovered that a molecule called QAPHA ((E)-3-(5-((2-cyanoquinolin-4-yl)(methyl)amino)-2-methoxyphenyl)-N-hydroxyacrylamide) has a dual function as both a tubulin polymerization and HDAC inhibitors...
April 11, 2024: Journal for Immunotherapy of Cancer
https://read.qxmd.com/read/38604815/oral-pd-l1-inhibitor-gs-4224-selectively-engages-pd-l1-high-cells-and-elicits-pharmacodynamic-responses-in-patients-with-advanced-solid-tumors
#18
JOURNAL ARTICLE
Jared M Odegard, Ahmed A Othman, Kai-Wen Lin, Adele Y Wang, Jonathan Nazareno, Oh Kyu Yoon, John Ling, Latesh Lad, P Rod Dunbar, Dung Thai, Edmond Ang, Nicholas Waldron, Sanjeev Deva
BACKGROUND: Checkpoint inhibitors targeting the programmed cell death 1 (PD-1)/programmed cell death 1 ligand 1 (PD-L1) pathway are effective therapies in a range of immunogenic cancer types. Blocking this pathway with an oral therapy could benefit patients through greater convenience, particularly in combination regimens, and allow flexible management of immune-mediated toxicities. METHODS: PD-L1 binding activity was assessed in engineered dimerization and primary cell target occupancy assays...
April 11, 2024: Journal for Immunotherapy of Cancer
https://read.qxmd.com/read/38604814/oma1-competitively-binds-to-hspa9-to-promote-mitophagy-and-activate-the-cgas-sting-pathway-to-mediate-gbm-immune-escape
#19
JOURNAL ARTICLE
Wen de Zhu, Jin Rao, Li Hua Zhang, Ka Ming Xue, Lin Li, Jun Jun Li, Qian Zhi Chen, Rong Fu
BACKGROUND: Immunotherapy with checkpoint inhibitors, especially those targeting programmed death receptor 1 (PD-1)/PD-1 ligand (PD-L1), is increasingly recognized as a highly promising therapeutic modality for malignancies. Nevertheless, the efficiency of immune checkpoint blockade therapy in treating glioblastoma (GBM) is constrained. Hence, it is imperative to expand our comprehension of the molecular mechanisms behind GBM immune escape (IE). METHODS: Protein chip analysis was performed to screen aberrantly expressed OMA1 protein in PD-1 inhibitor sensitive or resistant GBM...
April 11, 2024: Journal for Immunotherapy of Cancer
https://read.qxmd.com/read/38604813/autologous-human-preclinical-modeling-of-melanoma-interpatient-clinical-responses-to-immunotherapeutics
#20
JOURNAL ARTICLE
Yee Peng Phoon, Jared E Lopes, Lukas W Pfannenstiel, Claudia Marcela Diaz-Montero, Ye F Tian, Marc S Ernstoff, Pauline Funchain, Jennifer S Ko, Raymond Winquist, Heather C Losey, Jan Joseph Melenhorst, Brian R Gastman
BACKGROUND: Despite recent advances in immunotherapy, a substantial population of late-stage melanoma patients still fail to achieve sustained clinical benefit. Lack of translational preclinical models continues to be a major challenge in the field of immunotherapy; thus, more optimized translational models could strongly influence clinical trial development. To address this unmet need, we designed a preclinical model reflecting the heterogeneity in melanoma patients' clinical responses that can be used to evaluate novel immunotherapies and synergistic combinatorial treatment strategies...
April 11, 2024: Journal for Immunotherapy of Cancer
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