Article
Biochemistry & Molecular Biology
Sebastian Wirsching, Michael Fichter, Maximiliano L. Cacicedo, Katharina Landfester, Stephan Gehring
Summary: Cancer is a major cause of death globally. The search for innovative therapies is a key focus in medical research. Vaccine strategies targeting tumor-associated antigens have not yet achieved significant success, possibly due to the tumor microenvironment and regulatory T cells hindering efficacy. ASPH, a potential therapeutic target, is overexpressed in various tumors but minimally expressed in normal tissues. Computer analysis predicts that ASPH has four peptide sequences capable of stimulating regulatory T cell activity. Removing these regulatory T cell epitopes increases effector T cell responses and decreases the overall number of regulatory T cells. These findings suggest that screening and eliminating potential regulatory T cell epitopes can improve the efficacy of new vaccine candidates.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Chemistry, Medicinal
Minoru Tada, Michihiko Aoyama, Akiko Ishii-Watabe
Summary: T cell-redirecting bispecific antibodies (bsAbs) simultaneously bind tumor-associated antigens on tumor cells and CD3 on T cells, resulting in T cell-mediated cytotoxicity against tumor cells. This study found that the aggregates of bsAbs could directly activate immune cells and induce inflammatory responses. These findings suggest the potential risk of unwanted immune cell activation and inflammation due to the aggregation of bsAbs.
JOURNAL OF PHARMACEUTICAL SCIENCES
(2023)
Editorial Material
Oncology
Wolfgang A. Weber, Zohreh Varasteh, Katja Fritschle, Volker Morath
Summary: FAP-targeted therapies have shown limited success so far, but FAP imaging offers new opportunities for patient selection and monitoring tumor response.
CLINICAL CANCER RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Ju A. Shim, Yuna Jo, Hyunju Hwang, So Eun Lee, Dahyeon Ha, Jun Hwa Lee, Jayoung Kim, Parkyong Song, Dongjun Lee, Changwan Hong
Summary: This study investigated the roles of aminoacyl-tRNA synthetases (ARSs) in immune cells. The researchers found that translational fidelity affects immune cell responses and cellularity, and sti mutant inhibits TCR signaling, impeding T cell survival and responses. Additionally, B cell numbers were decreased in sti mice, but serum IgM, IgA, and IgE levels were higher.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Article
Immunology
Jiri Koutnik, Michael Leitges, Kerstin Siegmund
Summary: This study investigated the role of PKD3 in T cell activation and found that it is dispensable for T cell activation. The skewing in the T cell compartment observed in conventional PKD3-deficient mice seems to be mediated by T cell-extrinsic mechanisms.
FRONTIERS IN IMMUNOLOGY
(2022)
Editorial Material
Cell Biology
Gregory M. Chen, Jan Joseph Melenhorst, Kai Tan
Summary: CAR T cell therapies targeting CD19 and CD22 have shown success in treating B cell cancers, but not in non-B cell cancers. The interaction between CAR T cells and normal B cells may play a crucial role in determining clinical CAR T cell responses.
SCIENCE TRANSLATIONAL MEDICINE
(2022)
Article
Cell Biology
Longhui Zeng, Ivan Palaia, Andela Saric, Xiaolei Su
Summary: Phospholipase C gamma 1 (PLC gamma 1) promotes phase separation of LAT in the TCR pathway, directly cross-linking LAT through its two SH2 domains. PLC gamma 1 also protects LAT from dephosphorylation by CD45, and enhances LAT-dependent ERK activation and SLP76 phosphorylation. A nonmonotonic effect of PLC gamma 1 on LAT clustering was discovered, and computer simulations showed how cluster size is regulated by protein compositions. These results define a critical role of PLC gamma 1 in promoting phase separation of the LAT complex and TCR signal transduction.
JOURNAL OF CELL BIOLOGY
(2021)
Article
Multidisciplinary Sciences
Zebin Xiao, Leslie Todd, Li Huang, Estela Noguera-Ortega, Zhen Lu, Lili Huang, Meghan Kopp, Yue Li, Nimisha Pattada, Wenqun Zhong, Wei Guo, John Scholler, Maria Liousia, Charles-Antoine Assenmacher, Carl H. June, Steven M. Albelda, Ellen Pure
Summary: In preclinical PDAC models, the depletion of FAP-expressing cancer associated fibroblasts with FAP-targeted CAR T cells renders tumors more susceptible to sequential treatment with mesothelin-targeted CAR-T cells. These findings provide a strong rationale for combining tumor stroma- and malignant cell-targeted therapies in clinical trials.
NATURE COMMUNICATIONS
(2023)
Article
Chemistry, Medicinal
Kaiming Li, Yue Chen, Nianci Zhu, Sijia Chen, Meng Jia, Lingjing Xue, Meixi Hao, Can Zhang
Summary: Successful T-cell based immunotherapy usually relies on the activation of T cells. Current methods for assessing T cell activity are often labor-intensive and costly, and can't provide real-time detection. In this study, a cholesterol derived aggregation-induced emission (AIE) fluorescent probe (R-TPE-PEG-Chol) was developed for real-time detection of T cell activation.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Cell Biology
Jiri Koutnik, Verena Neururer, Thomas Gruber, Sebastian Peer, Natascha Hermann-Kleiter, William J. Olson, Verena Labi, Michael Leitges, Gottfried Baier, Kerstin Siegmund
Summary: The deficiency of PKD3 leads to a skewing of T cell compartment towards an activated phenotype in mice, but it is dispensable for naive CD4(+) T cell differentiation in vitro.
CELL COMMUNICATION AND SIGNALING
(2022)
Article
Chemistry, Analytical
Andreas Madsen, Oscar Mejias-Gomez, Lasse E. Pedersen, Kerstin Skovgaard, Peter Kristensen, Steffen Goletz
Summary: Simultaneous targeting of different antigens with bispecific antibodies (bsAbs) has high therapeutic potential but presents challenges in analysis. Flow-induced dispersion analysis (FIDA) allows in-depth characterization of bsAbs under near-native conditions, determining equilibrium dissociation constants and analyzing binding cooperativity. FIDA is a versatile tool with low material consumption and high matrix tolerability for format selection and characterization of complex protein therapeutics.
ANALYTICAL CHEMISTRY
(2022)
Article
Chemistry, Analytical
Andreas Madsen, Oscar Mejias-Gomez, Lasse E. Pedersen, Kerstin Skovgaard, Peter Kristensen, Steffen Goletz
Summary: FIDA technology enables in-depth characterization of bsAbs with diverse molecular architectures and valencies, analyzing their bispecific binding functionality without being affected by molecular format, making it a versatile tool for selecting and characterizing complex protein therapeutics.
ANALYTICAL CHEMISTRY
(2022)
Article
Biology
Talang Wang, Ruoyu Zhao, Junhong Zhi, Ziling Liu, Aiwei Wu, Zimei Yang, Weixu Wang, Ting Ni, Lili Jing, Ming Yu
Summary: Tox4 protein is a regulator of PP1 phosphatases with unknown function in development. In mice, conditional knockout of Tox4 reduces thymic cellularity, partially blocks T cell development, and decreases the ratio of CD8 to CD4 cells. Tox4 loss also impairs proliferation of the fast-proliferating DP blast population within DP cells through downregulation of genes critical for proliferation, and genes with high and low expression level are more dependent on Tox4. Mechanistically, Tox4 may facilitate transcriptional reinitiation and restrict elongation in a dephosphorylation-dependent manner, and it is an evolutionarily conserved regulator of transcriptional elongation and reinitiation. Tox4 controls T cell development in mice by regulating transcription of cell cycle regulation genes via PP1 phosphatases, independent of chromatin accessibility modulation.
COMMUNICATIONS BIOLOGY
(2023)
Article
Nanoscience & Nanotechnology
Yulin Du, Yifan Lyu, Jie Lin, Chunran Ma, Qiang Zhang, Yutong Zhang, Liping Qiu, Weihong Tan
Summary: We manipulated the intermembrane distance between antigen-presenting cells (APCs) and T cells using DNA nanostructures of different sizes. Our results show that the axial distance of the contact zone is critical for T-cell activation, likely through modulating protein reorganization and mechanical force.
NATURE NANOTECHNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Sonia Andre, Morgane Picard, Renaud Cezar, Florence Roux-Dalvai, Aurelie Alleaume-Butaux, Calaiselvy Soundaramourty, Andre Santa Cruz, Ana Mendes-Frias, Clarisse Gotti, Mickael Leclercq, Alexandre Nicolas, Alexandra Tauzin, Alexandre Carvalho, Carlos Capela, Jorge Pedrosa, Antonio Gil Castro, Lucy Kundura, Paul Loubet, Albert Sotto, Laurent Muller, Jean-Yves Lefrant, Claire Roger, Pierre-Geraud Claret, Sandra Duvnjak, Tu-Anh Tran, Gina Racine, Ouafa Zghidi-Abouzid, Pierre Nioche, Ricardo Silvestre, Arnaud Droit, Fabrizio Mammano, Pierre Corbeau, Jerome Estaquier
Summary: By comparing COVID-19 patients with healthy donors, the study found a strong correlation between T cell apoptosis and lymphopenia in severe cases. The plasma levels of soluble FasL (sFasL) and T cell surface expression of Fas/CD95 were positively correlated with T cell death and CD4 T cell counts. The study also identified modulations in the Bcl-2 family and demonstrated the potential of a pan-caspase inhibitor, Q-VD, to prevent T cell apoptosis and enhance Th1 transcripts.
CELL DEATH AND DIFFERENTIATION
(2022)
Review
Immunology
Sharad K. Mittal, Paul A. Roche
CURRENT OPINION IN IMMUNOLOGY
(2015)
Article
Biochemistry & Molecular Biology
Sharad K. Mittal, Kyung-Jin Cho, Satoshi Ishido, Paul A. Roche
JOURNAL OF BIOLOGICAL CHEMISTRY
(2015)
Article
Hematology
Q. Da, T. Shaw, S. Pradhan, P. A. Roche, M. A. Cruz, K. V. Vijayan
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2017)
Article
Multidisciplinary Sciences
Ofir Klein, Amit Roded, Neta Zur, Nurit P. Azouz, Olga Pasternak, Koret Hirschberg, Ilan Hammel, Paul A. Roche, Ayaka Yatsu, Mitsunori Fukuda, Stephen J. Galli, Ronit Sagi-Eisenberg
SCIENTIFIC REPORTS
(2017)
Article
Chemistry, Multidisciplinary
Hak-Sung Jung, Kyung-Jin Cho, Yeonee Seol, Yasuharu Takagi, Andrew Dittmore, Paul A. Roche, Keir C. Neuman
ADVANCED FUNCTIONAL MATERIALS
(2018)
Article
Biochemistry & Molecular Biology
Lei Lei, Joanna Bandola-Simon, Paul A. Roche
JOURNAL OF BIOLOGICAL CHEMISTRY
(2018)
Article
Biochemistry & Molecular Biology
Sunil Kaul, Sharad K. Mittal, Paul A. Roche
JOURNAL OF BIOLOGICAL CHEMISTRY
(2018)
Article
Biochemistry & Molecular Biology
Joanna Bandola-Simon, Paul A. Roche
MOLECULAR IMMUNOLOGY
(2019)
Article
Multidisciplinary Sciences
Candida Bhagwandin, Erin L. Ashbeck, Michael Whalen, Joanna Bandola-Simon, Paul A. Roche, Adam Szajman, Sarah Mai Truong, Betsy C. Wertheim, Yann C. Klimentidis, Satoshi Ishido, Benjamin J. Renquist, Lonnie Lybarger
Article
Biochemistry & Molecular Biology
Vasudha Agarwal, Pieu Naskar, Suchhanda Agasti, Gagandeep K. Khurana, Poonam Vishwakarma, Andrew M. Lynn, Paul A. Roche, Niti Puri
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
(2019)
Article
Nanoscience & Nanotechnology
Hak-Sung Jung, Kyung-Jin Cho, Seung-Jin Ryu, Yasuharu Takagi, Paul A. Roche, Keir C. Neuman
ACS APPLIED MATERIALS & INTERFACES
(2020)
Article
Immunology
Kyung-Jin Cho, Satoshi Ishido, Laurence C. Eisenlohr, Paul A. Roche
JOURNAL OF IMMUNOLOGY
(2020)
Article
Cell Biology
Kento Masaki, Yuhji Hiraki, Hiroka Onishi, Yuka Satoh, Paul A. Roche, Satoshi Tanaka, Kazuyuki Furuta
Article
Immunology
Hei Jung Kim, Joanna Bandola-Simon, Satoshi Ishido, Nathan W. Wong, Vishal N. Koparde, Maggie Cam, Paul A. Roche
Summary: Ubiquitination plays a crucial role in regulating MHC-II turnover on dendritic cells, impacting their ability to activate CD4 T cells and secrete IL-12. While MHC-II ubiquitination mutants exhibit functional defects, these can be reversed by activating DCs with LPS.
JOURNAL OF IMMUNOLOGY
(2021)
Article
Microbiology
Paul A. Roche, Peter Cresswell
MICROBIOLOGY SPECTRUM
(2016)