Article
Immunology
Chunyu Liu, Chuanfei Yu, Yalan Yang, Yongfei Cui, Feng Zhang, Lan Wang, Junzhi Wang
Summary: The study developed and validated a reporter gene assay to determine the bioactivity of anti-CTLA-4 mAbs, addressing the challenge faced by quality control labs. The assay demonstrated excellent specificity, accuracy, precision, linearity, and cell passage stability, making it suitable for characterization, batch release control, stability study, and biosimilar assessment of anti-CTLA-4 mAbs.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2021)
Article
Multidisciplinary Sciences
Matthew T. Campbell, Surena F. Matin, Alda L. Tam, Rahul A. Sheth, Kamran Ahrar, Rebecca S. Tidwell, Priya Rao, Jose A. Karam, Christopher G. Wood, Nizar M. Tannir, Eric Jonasch, Jianjun Gao, Amado J. Zurita, Amishi Y. Shah, Sonali Jindal, Fei Duan, Sreyashi Basu, Hong Chen, Alexsandra B. Espejo, James P. Allison, Shalini S. Yadav, Padmanee Sharma
Summary: In this pilot study of anti-CTLA-4 therapy with or without cryoablation in metastatic renal cell carcinoma patients, the combination is shown to be feasible and enhances immune cell infiltration in patients with metastatic clear cell histology. The findings highlight the potential of combining tremelimumab with cryotherapy to modulate the immune microenvironment in patients with metastatic clear cell histology to improve anti-tumor immune responses.
NATURE COMMUNICATIONS
(2021)
Article
Cell Biology
Mingyue Liu, Xu Wang, Xuexiang Du, Wei Wu, Yan Zhang, Peng Zhang, Chunxia Ai, Martin Devenport, Juanjuan Su, Musleh M. Muthana, Lishan Su, Yang Liu, Pan Zheng
Summary: Immune checkpoint inhibitors (ICIs) like nivolumab and ipilimumab show both antitumor responses and severe immune-related adverse events (irAEs), but treating irAEs without affecting the immunotherapeutic effect of ICIs remains a challenge. The use of abatacept to treat irAEs risks reducing the efficacy of anti-CTLA-4 immunotherapy. However, mutants of CTLA-4-Ig that bind to B7-1 and B7-2 can effectively treat irAEs without affecting cancer immunotherapy, making belatacept a potential drug to abrogate irAEs while preserving the therapeutic efficacy of CTLA-4-targeting ICIs.
SCIENCE TRANSLATIONAL MEDICINE
(2023)
Article
Oncology
Y. Nakamura, K. Namikawa, S. Yoshikawa, Y. Kiniwa, T. Maekawa, O. Yamasaki, T. Isei, S. Matsushita, M. Nomura, Y. Nakai, S. Fukushima, S. Saito, T. Takenouchi, R. Tanaka, H. Kato, A. Otsuka, T. Matsuya, N. Baba, K. Nagase, T. Inozume, N. Fujimoto, Y. Kuwatsuka, M. Onishi, T. Kaneko, T. Onuma, Y. Umeda, D. Ogata, A. Takahashi, M. Otsuka, Y. Teramoto, N. Yamazaki
Summary: In a study of advanced mucosal melanoma patients in Japan, it was found that there was no significant difference in efficacy between PD1 and PD1 + CTLA4, but the latter had a higher incidence of immune-related adverse events.
Article
Oncology
David B. Page, Kathryn Beal, Stefanie N. Linch, Kateri J. Spinelli, Micaela Rodine, Darragh Halpenny, Shanu Modi, Sujata Patil, Robert J. Young, Thomas Kaley, Taha Merghoub, David Redmond, Phillip Wong, Christopher A. Barker, Adi Diab, Larry Norton, Heather L. McArthur
Summary: This study explores the safety and efficacy of immune checkpoint blockade and radiotherapy in the management of breast cancer brain metastases. The results show that tremelimumab plus radiotherapy and trastuzumab is well-tolerated and has encouraging efficacy in HER2+ patients.
Review
Biochemistry & Molecular Biology
Laura Gamez-Diaz, Bodo Grimbacher
Summary: Autoimmune lymphoproliferative syndrome (ALPS) is an inherited non-malignant and noninfectious lymphoproliferative syndrome caused by mutations affecting the extrinsic apoptotic pathway. ALPS-like syndromes, such as CTLA-4 insufficiency and LRBA deficiency, exhibit similar clinical symptoms, characterized by low levels of CTLA-4 protein on the surface of Treg cells leading to autoimmune manifestations. Despite differences in inheritance and penetrance, these immune checkpoint deficiencies share overlapping but heterogeneous clinical presentations.
BIOMEDICAL JOURNAL
(2021)
Article
Oncology
Jonathan W. Goldman, Sarina A. Piha-Paul, Brendan Curti, Katrina S. Pedersen, Todd M. Bauer, Stefanie L. Groenland, Richard D. Carvajal, Vaishali Chhaya, Gray Kirby, Kelly McGlinchey, Scott A. Hammond, Katie Streicher, Danielle M. Townsley, Young Kwang Chae, Jens Voortman, Aurelien Marabelle, John Powderly
Summary: This study reported the safety and tolerability of combining MEDI0562 with durvalumab or tremelimumab in the treatment of advanced solid tumors. The results showed moderate toxicity in both treatment arms, but no clear efficacy signals were demonstrated. Partial responses were observed in some patients in the MEDI0562 + durvalumab arm.
CLINICAL CANCER RESEARCH
(2022)
Article
Chemistry, Medicinal
Pratibha Pandey, Fahad Khan, Huda A. Qari, Tarun Kumar Upadhyay, Abdulhameed F. Alkhateeb, Mohammad Oves
Summary: Immunotherapy has made significant progress in cancer treatment through blocking immunological checkpoint pathways. Recent studies have shown that combining immune checkpoint inhibitors with other anticancer drugs can improve their effectiveness. Immune checkpoint blockade also aids in inhibiting angiogenesis and enhancing the immune system's efficacy.
Article
Oncology
Yoshiyasu Umeda, Shusuke Yoshikawa, Yukiko Kiniwa, Takeo Maekawa, Osamu Yamasaki, Taiki Isei, Shigeto Matsushita, Motoo Nomura, Yasuo Nakai, Satoshi Fukushima, Shintaro Saito, Tatsuya Takenouchi, Ryo Tanaka, Hiroshi Kato, Atsushi Otsuka, Taisuke Matsuya, Natsuki Baba, Kotaro Nagase, Takashi Inozume, Takehiro Onuma, Yutaka Kuwatsuka, Noriki Fujimoto, Takahide Kaneko, Masazumi Onishi, Kenjiro Namikawa, Naoya Yamazaki, Yasuhiro Nakamura
Summary: The study found that the combination of radiotherapy (RT) with immune checkpoint inhibitors (ICIs) did not result in a significant survival benefit for patients with mucosal melanoma (MUM), although it may help improve local tumor control and relieve local symptoms.
EUROPEAN JOURNAL OF CANCER
(2021)
Review
Pharmacology & Pharmacy
Lucia Lisi, Pedro Miguel Lacal, Maria Martire, Pierluigi Navarra, Grazia Graziani
Summary: Immune checkpoint inhibitors have been investigated as an important approach for cancer immunotherapy, but combination therapy may lead to increased immune-related adverse events. The recent development of anti-CTLA-4 probodies and bispecific molecules targeting both CTLA-4 and PD-1 is considered a potential solution to overcome this drawback.
PHARMACOLOGICAL RESEARCH
(2022)
Article
Medicine, Research & Experimental
Jiawei Guan, Hongchuan Liu, Yan Chai, Jie Yu, Jian Yao, Jing Wang, Zhiwei Pan, Jing Zhang, Yuehua Zhou, Hui Liu, Sheng Yao, Jianxun Qi, Hui Feng, George. F. F. Gao, Qihui Wang, Yi Shi, Shuguang Tan
Summary: A humanized monoclonal antibody, JS007, has been developed with high binding affinity and T-cell activating efficiency to CTLA-4. It shows superior tumor suppression efficacy at low doses and adopts a unique binding mode compared to other anti-CTLA-4 antibodies.
Article
Oncology
Kyung-Soo Chun, Do-Hee Kim, Pawan Kumar Raut, Young-Joon Surh
Summary: Immune checkpoint inhibitors play a crucial role in cancer therapy by leveraging the body's own immune system to enhance anti-tumor responses. Studying the regulatory effects of natural phytochemicals on immune checkpoint protein networks and identifying potential therapeutic targets can improve treatment outcomes.
SEMINARS IN CANCER BIOLOGY
(2022)
Article
Medicine, Research & Experimental
Kazi J. Nahar, Felix Marsh-Wakefield, Robert V. Rawson, Tuba N. Gide, Angela L. Ferguson, Ruth Allen, Camelia Quek, Ines Pires da Silva, Stephen Tattersal, Christopher J. Kiely, Neomal Sandanayake, Matteo S. Carlino, Geoff McCaughan, James S. Wilmott, Richard A. Scolyer, Georgina V. Long, Alexander M. Menzies, Umaimainthan Palendira
Summary: Immune-related adverse events pose a significant obstacle to the success of immunotherapy. This study investigates the immune changes induced by combination anti-CTLA-4 and anti-PD-1 immunotherapy in patients with colitis. The researchers found distinct repertoire changes in patients with moderate-severe colitis, regardless of their antitumor response. The expansion of circulating monocytes and T cells was greater in patients with colitis, and specific T cell subsets were expanded in the inflamed regions of the colon. The data suggests that exaggerated innate and T cell responses contribute to colitis in susceptible patients.
Review
Pharmacology & Pharmacy
Laura I. I. Yousif, Anniek A. A. Tanja, Rudolf A. A. de Boer, Arco J. J. Teske, Wouter C. C. Meijers
Summary: Immune checkpoint inhibitors have potent anti-tumor effects but can cause cardiovascular immune-related adverse events. Therefore, studying the mechanisms of immune checkpoints in cardiovascular disease is crucial for preventing and treating immune-related cardiovascular adverse events.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Biotechnology & Applied Microbiology
Iris M. Hagemans, Peter J. Wierstra, Kas Steuten, Janneke D. M. Molkenboer-Kuenen, Duco van Dalen, Martin ter Beest, Johan M. S. van der Schoot, Olga Ilina, Martin Gotthardt, Carl G. Figdor, Ferenc A. Scheeren, Sandra Heskamp, Martijn Verdoes
Summary: A set of molecularly defined multimodal antibody-based PD-L1 imaging agents were synthesized and validated for multiscale monitoring of PD-L1 expression and localization. PEGylation of the Fab fragment improved its half-life and tumor uptake. PD-L1 in tumors was clearly visualized by SPECT/CT and whole body fluorescence imaging. The imaging agent's intratumoral localization could be determined with cellular resolution using fluorescent microscopy.
JOURNAL OF NANOBIOTECHNOLOGY
(2022)
Article
Immunology
Theinmozhi Arulraj, Sebastian C. Binder, Michael Meyer-Hermann
Summary: Follicular dendritic cells play a crucial role in retaining immune complexes for prolonged periods and supporting germinal center reactions. The cycling of immune complexes on FDCs impacts antigen protection and influences germinal center dynamics. Blocking antigen cycling could potentially terminate the germinal center reaction and decrease plasma cell production.
JOURNAL OF IMMUNOLOGY
(2021)
Review
Immunology
Theinmozhi Arulraj, Sebastian C. Binder, Philippe A. Robert, Michael Meyer-Hermann
Summary: Germinal Centres (GCs) are structures in secondary lymphoid organs where B cell affinity maturation takes place following infection, but the natural termination of GC reaction lacks a clear mechanistic understanding.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Cell Biology
Theinmozhi Arulraj, Sebastian C. Binder, Michael Meyer-Hermann
Summary: Germinal centers (GCs) are transient structures in secondary lymphoid organs where B cells undergo affinity maturation to produce high affinity memory and plasma cells. The lifetime of GC responses is a critical factor limiting the extent of affinity maturation and efficiency of antibody responses. Individual GCs may have varying lifetimes due to factors like antigen availability and founder cell composition, impacting overall GC responses in a primary immune response.
Article
Biology
Alaa M. Elgohary, Abdo A. Elfiky, Khaled Barakat
Summary: Mucormycosis, a rare and deadly fungal infection, was declared an epidemic during the second wave of the COVID-19 pandemic in India. With a mortality rate exceeding 40%, CotH3 protein is identified as a crucial virulence factor in Mucormycosis.
COMPUTERS IN BIOLOGY AND MEDICINE
(2021)
Article
Biochemistry & Molecular Biology
Saad S. Dahham, Yasser Tabana, Muhammad Asif, Marawan Ahmed, Dinesh Babu, Loiy E. Hassan, Mohamed B. Khadeer Ahamed, Doblin Sandai, Khaled Barakat, Arno Siraki, Amin M. S. A. Majid
Summary: The study demonstrated that BCP exhibited strong anti-angiogenic activity by blocking the migration of endothelial cells, tube-like network formation, suppression of VEGF secretion, and sprouting of microvessels. BCP also deformed the vascularization architecture in a chick embryo chorioallantoic membrane assay and showed a significant reduction in tumor growth in xenograft models by inducing apoptosis and modulating gene expressions related to cell survival and proliferation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Immunology
Theinmozhi Arulraj, Sebastian C. Binder, Michael Meyer-Hermann
Summary: The mechanisms of germinal center shutdown are still unclear. This study uses a mathematical model to identify several mechanisms that can promote germinal center contraction and shutdown, including antigen consumption, antigen masking, alterations in cell differentiation and proliferation capacity. In addition, the study proposes experimental methods to further investigate the mechanistic basis of germinal center shutdown.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Marawan Ahmed, Aravindhan Ganesan, Khaled Barakat
Summary: Small molecules targeting hPD-L1 protein have emerged as a promising new generation of immune checkpoints' inhibitors. This study provides an in-depth computational structural analysis of the interactions between five small molecules and hPD-L1, shedding light on the dynamics and molecular mechanisms driving their complex formation. The results highlight the importance of a terminal phenyl ring in hPD-L1 inhibitors.
Article
Biochemistry & Molecular Biology
Mowaffaq Adam Ahmed Adam, Laina Zarisa Muhd Kamal, Mahibub Kanakal, Dinesh Babu, Saad Sabbar Dahham, Yasser Tabana, Bronwyn Lok, Brittany M. Bermoy, Muhammad Amir Yunus, Leslie Thian Lung Than, Khaled Barakat, Doblin Sandai
Summary: This study investigated the effects of the fungal toxin AB1 on breast cancer cells and normal breast cells, and found that AB1 can increase the risk of breast cancer development by altering gene expression and epigenetic levels.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Polymer Science
Frage Abookleesh, Farag E. S. Mosa, Khaled Barakat, Aman Ullah
Summary: This study describes a computer-aided molecular design platform to rank and analyze the molecular interactions of different additives with plant proteins. The findings provide insights into protein-additive interactions and can guide the design of high-performance polymeric materials at the molecular level.
Article
Biology
Maryam Jama, Marawan Ahmed, Anna Jutla, Carson Wiethan, Jitendra Kumar, Tae Chul Moon, Frederick West, Michael Overduin, Khaled H. Barakat
Summary: This study utilized computational tools to screen over 6 million compounds and identified three potent allosteric inhibitors of SHP2. The binding affinities of these inhibitors to SHP2 were measured and found to be in the nanomolar range, suggesting their potential as improved allosteric inhibitors of SHP2.
COMPUTERS IN BIOLOGY AND MEDICINE
(2023)
Article
Multidisciplinary Sciences
Coraline Mlynarczyk, Matt Teater, Juhee Pae, Christopher R. Chin, Ling Wang, Theinmozhi Arulraj, Darko Barisic, Antonin Papin, Kenneth B. Hoehn, Ekaterina Kots, Jonatan Ersching, Arnab Bandyopadhyay, Ersilia Barin, Hui Xian Poh, Chiara M. Evans, Amy Chadburn, Zhengming Chen, Hao Shen, Hannah M. Isles, Benedikt Pelzer, Ioanna Tsialta, Ashley S. Doane, Huimin Geng, Muhammad Hassan Rehman, Jonah Melnick, Wyatt Morgan, Diu T. T. Nguyen, Olivier Elemento, Michael G. Kharas, Samie R. Jaffrey, David W. Scott, George Khelashvili, Michael Meyer-Hermann, Gabriel D. Victora, Ari Melnick
Summary: Multicellular life relies on altruistic cooperation among cells. However, a study found that mutations in the BTG1 gene disrupt a crucial mechanism that limits B cell fitness during antibody affinity maturation, leading to the emergence of aggressive lymphomas.
Article
Cell Biology
Theinmozhi Arulraj, Sebastian C. Binder, Michael Meyer-Hermann
Summary: In this study, computer simulations were used to investigate the role of soluble antibodies in the interaction between germinal centers (GCs). The findings suggest that intense interactions by soluble antibodies can limit the magnitude and lifetime of GC responses, and also lead to a bias in epitope recognition. The study also highlights the importance of GC-GC interactions in the affinity maturation towards antigenic variants during an ongoing GC reaction.
Review
Biology
Bronwyn Lok, Dinesh Babu, Yasser Tabana, Saad Sabbar Dahham, Mowaffaq Adam Ahmed Adam, Khaled Barakat, Doblin Sandai
Summary: The guava tree has long been used in traditional medicine to treat various ailments. Recent studies have shown that it exhibits anticancer activity, making it a potential alternative or adjuvant treatment for human cancers. In vitro and in vivo studies have demonstrated that extracts from the guava plant selectively suppress the growth of human cancer cells without harming normal cells. The availability of the plant also makes it a viable option for cancer treatment in developing countries.
Article
Oncology
Hanwen Wang, Theinmozhi Arulraj, Holly Kimko, Aleksander S. Popel
Summary: QSP models can be used to generate virtual patients and predict drug response. This study used immunogenomic data and pharmacokinetic data to generate virtual patients for non-small cell lung cancer (NSCLC) and predicted clinical response to PD-L1 inhibition.
NPJ PRECISION ONCOLOGY
(2023)
Article
Multidisciplinary Sciences
Theinmozhi Arulraj, Hanwen Wang, Leisha A. Emens, Cesar A. Santa-Maria, Aleksander S. Popel
Summary: This study developed a quantitative systems pharmacology model based on transcriptome information to predict and identify response to anti-PD-1 therapy in patients with triple-negative breast cancer. The results suggest that certain features can serve as biomarkers individually or in combination to predict treatment response and guide potential therapeutic strategies.