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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
#2
JOURNAL ARTICLE
Antonio Tapia-Galisteo, Iñigo Sánchez-Rodríguez, Javier Narbona, Patricia Iglesias-Hernández, Saray Aragón-García, Anaïs Jiménez-Reinoso, Marta Compte, Shaukat Khan, Takeshi Tsuda, Patrick Chames, Javier Lacadena, Luis Álvarez-Vallina, Laura Sanz
T cell-based immunotherapies for solid tumors have not achieved the clinical success observed in hematological malignancies, partially due to the immunosuppressive effect promoted by the tumor microenvironment, where PD-L1 and TGF-β play a pivotal role. However, durable responses to immune checkpoint inhibitors remain limited to a minority of patients, while TGF-β inhibitors have not reached the market yet. Here, we describe a bispecific antibody for dual blockade of PD-L1 and TFG-β, termed AxF (scFv)2 , under the premise that combination with T cell redirecting strategies would improve clinical benefit...
2024: Oncoimmunology
#3
JOURNAL ARTICLE
Yuki Masuda, Shizuka Yamashita, Yoshiaki Nakayama, Ryohei Shimizu, Morichika Konishi
Trastuzumab, an anti-HER2 monoclonal antibody, is the mainstay treatment for of HER2-positive breast cancer. However, trastuzumab resistance is often observed during treatment. Therefore, new therapeutic strategies are needed to enhance the clinical benefits of trastuzumab. Maitake β-glucan MD-Fraction, isolated from Grifola frondosa, inhibits tumor growth by enhancing immune responses. In this study, we examined the effect of MD-Fraction on trastuzumab treatment of HER2-positive breast cancer. MD-Fraction did not directly inhibit the survival of HER2-positive breast cancer cells, alone or in the presence of trastuzumab in vitro...
2024: Biological & Pharmaceutical Bulletin
#4
JOURNAL ARTICLE
Samuel J Holzmayer, Joseph Kauer, Jonas Mauermann, Tobias Roider, Melanie Märklin
B cell acute lymphoblastic leukemia (B-ALL) is characterized by an accumulation of malignant precursor cells. Treatment consists of multiagent chemotherapy followed by allogeneic stem cell transplantation in high-risk patients. In addition, patients bearing the BCR-ABL1 fusion gene receive concomitant tyrosine kinase inhibitor (TKI) therapy. On the other hand, monoclonal antibody therapy is increasingly used in both clinical trials and real-world settings. The introduction of rituximab has improved the outcomes in CD20 positive cases...
March 26, 2024: Cancers
#5
JOURNAL ARTICLE
Catherine Riou, Jinal N Bhiman, Yashica Ganga, Shobna Sawry, Frances Ayres, Richard Baguma, Sashkia R Balla, Ntombi Benede, Mallory Bernstein, Asiphe S Besethi, Sandile Cele, Carol Crowther, Mrinmayee Dhar, Sohair Geyer, Katherine Gill, Alba Grifoni, Tandile Hermanus, Haajira Kaldine, Roanne S Keeton, Prudence Kgagudi, Khadija Khan, Erica Lazarus, Jean Le Roux, Gila Lustig, Mashudu Madzivhandila, Siyabulela F J Magugu, Zanele Makhado, Nelia P Manamela, Qiniso Mkhize, Paballo Mosala, Thopisang P Motlou, Hygon Mutavhatsindi, Nonkululeko B Mzindle, Anusha Nana, Rofhiwa Nesamari, Amkele Ngomti, Anathi A Nkayi, Thandeka P Nkosi, Millicent A Omondi, Ravindre Panchia, Faeezah Patel, Alessandro Sette, Upasna Singh, Strauss van Graan, Elizabeth M Venter, Avril Walters, Thandeka Moyo-Gwete, Simone I Richardson, Nigel Garrett, Helen Rees, Linda-Gail Bekker, Glenda Gray, Wendy A Burgers, Alex Sigal, Penny L Moore, Lee Fairlie
We report the safety and immunogenicity of fractional and full dose Ad26.COV2.S and BNT162b2 in an open label phase 2 trial of participants previously vaccinated with a single dose of Ad26.COV2.S, with 91.4% showing evidence of previous SARS-CoV-2 infection. A total of 286 adults (with or without HIV) were enrolled >4 months after an Ad26.COV2.S prime and randomized 1:1:1:1 to receive either a full or half-dose booster of Ad26.COV2.S or BNT162b2 vaccine. B cell responses (binding, neutralization and antibody dependent cellular cytotoxicity-ADCC), and spike-specific T-cell responses were evaluated at baseline, 2, 12 and 24 weeks post-boost...
2024: PLOS Glob Public Health
#6
JOURNAL ARTICLE
Austin T K Hoke, Yoko Takahashi, Michelle R Padget, Javier Gomez, Moran Amit, Jared Burks, Diana Bell, Tongxin Xie, Patrick Soon-Shiong, James W Hodge, Ehab Y Hanna, Nyall R London
PURPOSE: Sinonasal undifferentiated carcinoma (SNUC) is a rare, aggressive malignancy of the sinonasal cavity with poor prognosis and limited treatment options. To investigate the potential for SNUC sensitivity to combinatory immunotherapy, we performed in vitro studies with SNUC cell lines and used multi-spectral immunofluorescence to characterize the in vivo patient SNUC tumor immune microenvironment (TIME). EXPERIMENTAL DESIGN: Human-derived SNUC cell lines were used for in vitro studies of tumor cell susceptibility to natural killer (NK) cell-based immunotherapeutic strategies...
April 8, 2024: Translational Oncology
#7
REVIEW
Megan Yuan, Wenjun Wang, Isobel Hawes, Junwen Han, Zhenyu Yao, Alice Bertaina
Comprising only 1-10% of the circulating T cell population, γδT cells play a pivotal role in cancer immunotherapy due to their unique amalgamation of innate and adaptive immune features. These cells can secrete cytokines, including interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α), and can directly eliminate tumor cells through mechanisms like Fas/FasL and antibody-dependent cell-mediated cytotoxicity (ADCC). Unlike conventional αβT cells, γδT cells can target a wide variety of cancer cells independently of major histocompatibility complex (MHC) presentation and function as antigen-presenting cells (APCs)...
2024: Frontiers in Immunology
#8
JOURNAL ARTICLE
Getraud Stocker, Ulrich Hacker, Florian Lordick
Cancers of gastrointestinal tract make up the largest group of solid tumour diseases in Germany. The prognosis at diagnosis is often critical. Drug therapies reduce the risk of relapse after resection and can halt the progression of metastatic disease. Immunotherapies contribute increasingly to the treatment of gastrointestinal tumours. Monoclonal antibodies (mAB) against surface receptors from the epidermal growth factor receptor family (EGFR, Her2) are well established. The effect is partly based on the interruption of the oncogenic downstream signalling cascades and partly on immune effector mechanisms such as antibody-dependent cellular cytotoxicity...
April 2024: Deutsche Medizinische Wochenschrift
#9
JOURNAL ARTICLE
Dafei Chai, Xu Wang, Praveen Neeli, Shan Zhou, Xingfang Yu, Kanaga Sabapathy, Yong Li
The tumor suppressor p53 is the most common mutated gene in cancer, with the R175H as the most frequent p53 missense mutant. However, there are currently no approved targeted therapies or immunotherapies against mutant p53. Here, we characterized and investigated a monoclonal antibody (mAb) that recognizes the mutant p53-R175H for its affinity, specificity, and activity against tumor cells in vitro . We then delivered DNA plasmids expressing the anti-R175H mAb or a bispecific antibody (BsAb) into mice to evaluate their therapeutic effects...
July 2024: Genes & Diseases
#10
JOURNAL ARTICLE
Zhe Ma, Zhenxing Zhou, Wenwen Duan, Gaofeng Yao, Shimei Sheng, Sidou Zong, Xin Zhang, Changkui Li, Yuanyuan Liu, Fengting Ou, Maha Raja Dahar, Yanshan Huang, Lushan Yu
BACKGROUND: Claudin 18.2 (CLDN18.2) is a highly anticipated target for solid tumor therapy, especially in advanced gastric carcinoma and pancreatic carcinoma. The T cell engager targeting CLDN18.2 represents a compelling strategy for enhancing anti-cancer efficacy. METHODS: Based on the in-house screened anti-CLDN18.2 VHH, we have developed a novel tri-specific T cell engager targeting CLDN18.2 for gastric and pancreatic cancer immunotherapy. This tri-specific antibody was designed with binding to CLDN18...
March 30, 2024: Cancer Immunology, Immunotherapy: CII
#11
JOURNAL ARTICLE
Jiawei Zhou, Can Liu, Yu Tang, Zhongbo Li, Yanguang Cao
Despite the specificity and effectiveness of antibody therapy, resistance to treatment remains a major barrier for their broad clinical applications. While genetic mutations are known to be critical, the impact of non-genetic mechanisms, such as epigenetic changes and phenotypic adaptations, on resistance to antibody-dependent cellular cytotoxicity (ADCC) is not fully understood. Our study investigated the non-genetic resistance mechanisms that colorectal cancer cells develop against cetuximab and the resulting ADCC pressure...
April 19, 2024: IScience
#12
JOURNAL ARTICLE
Zhi-Xiong Huang, Dian-Chao Lin, Hua-Ying Zhang, Meng-Jie Yang, Jia-Hao Chen, Xin-Yu Ding, Song-Juan Dai, Yi-Huang Hong, Gui-Shuang Liang, Qi-Yuan Li, Qiong-Hua Chen
Endometriosis is defined as an oestrogen-dependent and inflammatory gynaecological disease of which the pathogenesis remains unclear. This study aimed to investigate the cellular heterogeneity and reveal the effect of CD8+ T cells on the progress of endometriosis. Three ovarian endometriosis patients were collected, and single-cell RNA sequencing (scRNA-seq) progressed and delineated the cellular landscape of endometriosis containing five cell clusters. The endometrial cells (EMCs) were the major component, of which the mesenchymal cells were preponderant and characterized with increased inflammation and oestrogen synthesis in endometriosis...
March 27, 2024: Immunology
#13
REVIEW
Merit Bartels, Eric Sala Solé, Lotte M Sauerschnig, Ger T Rijkers
Before the emergence of SARS-CoV-1, MERS-CoV, and most recently, SARS-CoV-2, four other coronaviruses (the alpha coronaviruses NL63 and 229E and the beta coronaviruses OC43 and HKU1) had already been circulating in the human population. These circulating coronaviruses all cause mild respiratory illness during the winter seasons, and most people are already infected in early life. Could antibodies and/or T cells, especially against the beta coronaviruses, have offered some form of protection against (severe) COVID-19 caused by infection with SARS-CoV-2? Related is the question of whether survivors of SARS-CoV-1 or MERS-CoV would be relatively protected against SARS-CoV-2...
March 19, 2024: Microorganisms
#14
JOURNAL ARTICLE
Ilse Roodink, Maartje van Erp, Andra Li, Sheila Potter, Sander M J van Duijnhoven, Milou Smits, Arthur J Kuipers, Bert Kazemier, Bob Berkeveld, Ellen van Geffen, Britte S de Vries, Danielle Rijbroek, Bianca Boers, Sanne Meurs, Wieger Hemrika, Alexandra Thom, Barry N Duplantis, Roland A Romijn, Jeremy S Houser, Jennifer L Bath, Yasmina N Abdiche
Therapeutic antibodies (Abs) which act on a broader range of epitopes may provide more durable protection against the genetic drift of a target, typical of viruses or tumors. When these Abs exist concurrently on the targeted antigen, several mechanisms of action (MoAs) can be engaged, boosting therapeutic potency. This study selected combinations of four and five Abs with non- or partially overlapping epitopes to the SARS-CoV-2 spike glycoprotein, on or outside the crucial receptor binding domain (RBD), to offer resilience to emerging variants and trigger multiple MoAs...
March 13, 2024: Biomedicines
#15
JOURNAL ARTICLE
Hesham M Shehata, Pranay Dogra, Sarah Gierke, Patrick Holder, Shomyseh Sanjabi
IL-15 has shown preclinical activity by enhancing the functional maturation of natural killer (NK) cells. Clinical evaluation of the potential anticancer activity of most cytokines, including IL-15, has been limited by low tolerability and rapid in vivo clearance. Efbalropendekin Alfa (XmAb24306) is a soluble IL15/IL15-receptor alpha heterodimer complex fused to a half-life extended Fc domain (IL15/IL15Rα-Fc), engineered with mutations to reduce IL-15 affinity for CD122. Reduced affinity drives lower potency, leading to prolonged pharmacodynamic response in cynomolgus monkeys...
2024: Frontiers in Immunology
#16
JOURNAL ARTICLE
Hadeel T Zedan, Maria K Smatti, Duaa W Al-Sadeq, Hebah A Al Khatib, Eleonora Nicolai, Massimo Pieri, Sergio Bernardini, Ali Ait Hssain, Sara Taleb, Hamda Qotba, Khodr Issa, Laith J Abu Raddad, Asmaa A Althani, Gheyath K Nasrallah, Hadi M Yassine
Neutralizing antibodies (NAbs) are elicited after infection and vaccination and have been well studied. However, their antibody-dependent cellular cytotoxicity (ADCC) functionality is still poorly characterized. Here, we investigated ADCC activity in convalescent sera from infected patients with wild-type (WT) severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) or omicron variant compared with three coronavirus disease 2019 (COVID-19) vaccine platforms and postvaccination breakthrough infection (BTI)...
March 2024: Journal of Medical Virology
#17
JOURNAL ARTICLE
Elena Muraro, Barbara Montico, Benedict Lum, Francesca Colizzi, Giorgio Giurato, Annamaria Salvati, Roberto Guerrieri, Aurora Rizzo, Elisa Comaro, Vincenzo Canzonieri, Andrea Anichini, Michele Del Vecchio, Roberta Mortarini, Massimo Milione, Alessandro Weisz, Maria Antonietta Pizzichetta, Fiona Simpson, Riccardo Dolcetti, Elisabetta Fratta, Luca Sigalotti
INTRODUCTION: About 50% of cutaneous melanoma (CM) patients present activating BRAF mutations that can be effectively targeted by BRAF inhibitors (BRAFi). However, 20% of CM patients exhibit intrinsic drug resistance to BRAFi, while most of the others develop adaptive resistance over time. The mechanisms involved in BRAFi resistance are disparate and globally seem to rewire the cellular signaling profile by up-regulating different receptor tyrosine kinases (RTKs), such as the epidermal growth factor receptor (EGFR)...
2024: Frontiers in Immunology
#18
JOURNAL ARTICLE
Omar Chuquisana, Frauke Stascheit, Christian W Keller, Maja Pučić-Baković, Anne-Marie Patenaude, Gordan Lauc, Socrates Tzartos, Heinz Wiendl, Nick Willcox, Andreas Meisel, Jan D Lünemann
BACKGROUND AND OBJECTIVES: Antibodies (Abs) specific for the low-density lipoprotein receptor-related protein 4 (LRP4) occur in up to 5% of patients with myasthenia gravis (MG). The objective of this study was to profile LRP4-Ab effector actions. METHODS: We evaluated the efficacy of LRP4-specific compared with AChR-specific IgG to induce Ab-dependent cellular phagocytosis (ADCP), Ab-dependent cellular cytotoxicity (ADCC), and Ab-dependent complement deposition (ADCD)...
May 2024: Neurology® Neuroimmunology & Neuroinflammation
#19
JOURNAL ARTICLE
Harrison D Collier-Bain, Annabelle Emery, Adam J Causer, Frankie F Brown, Rebecca Oliver, David Dutton, Josephine Crowe, Daniel Augustine, John Graby, Shoji Leach, Rachel Eddy, Daniela Rothschild-Rodriguez, Juliet C Gray, Mark S Cragg, Kirstie L Cleary, Sally Moore, James Murray, James E Turner, John P Campbell
Chronic lymphocytic leukaemia (CLL) is characterised by the clonal proliferation and accumulation of mature B-cells and is often treated with rituximab, an anti-CD20 monoclonal antibody immunotherapy. Rituximab often fails to induce stringent disease eradication, due in part to failure of antibody-dependent cellular cytotoxicity which relies on natural killer (NK)-cells binding to rituximab-bound CD20 on B-cells. CLL cells are diffusely spread across lymphoid and other bodily tissues, and ADCC resistance in survival niches may be due to several factors including low NK-cell frequency and a suppressive stromal environment that promotes CLL cell survival...
March 17, 2024: Brain, Behavior, and Immunity
#20
JOURNAL ARTICLE
Franz Mai, Wendy Bergmann, Emil C Reisinger, Brigitte Müller-Hilke
The corona virus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome corona-virus 2 (SARS-CoV-2) spurred a worldwide race for the development of an efficient vaccine. Various strategies were pursued; however, the first vaccines to be licensed presented the SARS-CoV-2 spike protein either in the context of a non-replicating adenoviral vector or as an mRNA construct. While short-term efficacies have extensively been characterized, the duration of protection, the need for repeated boosting, and reasonable vaccination intervals have yet to be defined...
March 19, 2024: Journal of Virology
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