Review
Immunology
Roy A. Mariuzza, Daichao Wu, Brian G. Pierce
Summary: This review summarizes recent studies on the structural and biophysical aspects of T cell receptor (TCR) recognition of shared cancer neoantigens derived from oncogenes. The findings reveal the correlation between different mutations and the antigen presentation, and discuss the potential of TCR-mimic antibodies as an alternative to TCRs for targeting cancer neoantigens. Additionally, the review highlights recent computational advances and the significance of structural information in predicting neoepitope immunogenicity.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Akhil Shukla, Maryse Cloutier, Madanraj Appiya Santharam, Sheela Ramanathan, Subburaj Ilangumaran
Summary: The immune system constantly monitors and eliminates cancerous cells, with CD8(+) cytotoxic T lymphocytes playing a key role in tumor cell killing. Cancer cells evade immune surveillance by downregulating MHC-I and key proteins of the antigen processing and presentation machinery. NLRC5 has been identified as the key transcriptional activator of MHC-I and APM genes, and genetic lesions and epigenetic modifications of NLRC5 are common causes of MHC-I defects in cancers.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biotechnology & Applied Microbiology
Thamotharampillai Dileepan, Deepali Malhotra, Dmitri I. Kotov, Elizabeth M. Kolawole, Peter D. Krueger, Brian D. Evavold, Marc K. Jenkins
Summary: Engineered peptide:MHCII tetramers with enhanced CD4 binding outperform traditional tetramers in detecting antigen-specific CD4(+) T cells, allowing for identification of more T cells in immunized mice. These new reagents provide a deeper understanding of the T cell repertoire.
NATURE BIOTECHNOLOGY
(2021)
Article
Multidisciplinary Sciences
Kimberly G. Laffey, Robert J. Stiles, Melissa J. Ludescher, Tessa R. Davis, Shariq S. Khwaja, Richard J. Bram, Peter J. Wettstein, Venkataraman Ramachandran, Christopher A. Parks, Edwin E. Reyes, Alejandro Ferrer, Jenna M. Canfield, Cory E. Johnson, Richard D. Hammer, Diana Gil, Adam G. Schrum
Summary: During normal T cell development, a low-frequency population of early all TCR+ DN cells is present, which requires CD3δ for their generation/detection. These cells can respond to MHC and display coreceptor-independent MHC reactivity. It has been observed that these cells are susceptible to T-ALL transformation.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Review
Immunology
Mara Cenerenti, Margaux Saillard, Pedro Romero, Camilla Jandus
Summary: The article reviews the discovery and characterization of cytotoxic CD4 T cells, and describes their mechanisms of cytotoxicity. The importance of these cells in disease conditions, particularly in cancer, is emphasized, and insights on how to exploit these cells in immunotherapy are provided.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Health Care Sciences & Services
Josephine G. M. Strijker, Ronja Pscheid, Esther Drent, Jessica J. F. van der Hoek, Bianca Koopmans, Kimberley Ober, Sander R. van Hooff, Waleed M. Kholosy, Annelisa M. Cornel, Chris Coomans, Andrea Bisso, Marleen M. van Loenen, Jan J. Molenaar, Judith Wienke
Summary: A novel T cell-based immunotherapy approach for neuroblastoma, utilizing TEG002, showed promising results in recognizing and killing target cells independent of MHC-I expression. The efficacy of TEG002 treatment was superior to untransduced alpha beta-T cells or endogenous gamma delta-T cells in killing neuroblastoma organoids, indicating its potential as a new treatment option for a subset of patients.
JOURNAL OF PERSONALIZED MEDICINE
(2021)
Review
Immunology
Yifan Xu, Jin Jiang, Yutong Wang, Wei Wang, Haokun Li, Wenyu Lai, Zhipeng Zhou, Wei Zhu, Zheng Xiang, Zhiming Wang, Zhe Zhu, Lingfeng Yu, Xiaolan Huang, Hua Zheng, Sha Wu
Summary: Gynecologic malignancies are leading causes of death among women worldwide, and adoptive T cell therapy using engineered T cells has shown promising efficacy in treating tumors. Ongoing research is driving the application of this therapy in the treatment of gynecologic malignancies.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Oncology
Yikai Zhang, Zhipeng Liu, Wei Wei, Yangqiu Li
Summary: This article summarizes the current advances in TCR-T cell therapy and their potential advantages for solid tumor immunotherapy.
EXPERIMENTAL HEMATOLOGY & ONCOLOGY
(2022)
Article
Biotechnology & Applied Microbiology
Kenji Sugata, Yukiko Matsunaga, Yuki Yamashita, Munehide Nakatsugawa, Tingxi Guo, Levon Halabelian, Yota Ohashi, Kayoko Saso, Muhammed A. Rahman, Mark Anczurowski, Chung-Hsi Wang, Kenji Murata, Hiroshi Saijo, Yuki Kagoya, Dalam Ly, Brian D. Burt, Marcus O. Butler, Tak W. Mak, Naoto Hirano
Summary: By combining molecular biological and immunological techniques, this study successfully cloned sequences encoding HLA-DP, HLA-DQ, and HLA-DR molecules with enhanced CD4 binding affinity and produced affinity-matured class II dimers that stain antigen-specific T cells better than conventional multimers. These affinity-matured class II dimers will aid in the investigation of human CD4(+) T-cell responses, providing a comprehensive library of dimers for HLA-DP, HLA-DQ, and HLA-DR alleles. The readily detectable CD4(+) T cells with class II MHC dimers are crucial for studying human immune responses.
NATURE BIOTECHNOLOGY
(2021)
Review
Immunology
Dmitriy S. S. Kravtsov, Amy K. K. Erbe, Paul M. M. Sondel, Alexander L. L. Rakhmilevich
Summary: It is well established that CD8+ T cells are effector cells in the adaptive immune response against tumors, while CD4+ T cells can either help or suppress the generation of CD8+ cytotoxic T cells. However, recent evidence has shown that CD4+ T cells can also play a role in antitumor immunity by directly killing tumor cells, activating innate immune cells, or reducing tumor angiogenesis.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Immunology
Fang Wei, Xiao-Xia Cheng, John Zhao Xue, Shao-An Xue
Summary: Immunotherapy of cancer, especially TCR-T, has shown remarkable progress in recent years. This review summarizes the challenges and opportunities of TCR-T and proposes a strategy of combining different treatments to target solid tumors effectively.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
Georgia F. Papadaki, Omar Ani, Tyler J. Florio, Michael C. Young, Julia N. Danon, Yi Sun, Devin Dersh, Nikolaos G. Sgourakis
Summary: Major Histocompatibility Complex class I (MHC-I) molecules present self, viral or aberrant epitopic peptides to T cell receptors (TCRs) through interactions with complementarity-determining regions and MHC-I heavy chain 'framework' residues. In this study, using structural data from peptide:MHC-I and pMHC:TCR structures, the researchers identified important residues for peptide and/or TCR binding and proposed a fixed-backbone computational design approach for engineering synthetic molecules with desired properties. Experimental results showed that chimeric molecules bridging divergent HLA alleles can bind selected peptide antigens, highlighting the potential of these synthetic HLA molecules as screening probes for peptide-centric interactions with TCRs and other therapeutic modalities.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Nina Geng, Tuo Hu, Chunbo He
Summary: Immune checkpoint blockade therapies show durable responses in a subset of colorectal cancer patients, but the majority do not respond. Our study suggests that DDX60 may regulate MHC-I expression in colorectal cancer, and targeting DDX60 could potentially improve the efficacy of immunotherapy.
Review
Biochemistry & Molecular Biology
Elena Shklovskaya, Helen Rizos
Summary: It is well acknowledged that the immune system plays a role in controlling tumor growth, but tumors can escape immune surveillance through mechanisms like downregulation or loss of MHC-I molecules. This review examines the dysregulation of MHC-I expression in cancer, the nature of MHC-I-bound antigenic peptides, and discusses therapeutic strategies to address MHC-I deficiency in solid tumors with a focus on NK cells and CD4 T cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Cell Biology
Aude De Gassart, Kieu-Suong Le, Patrick Brune, Sophie Agaugue, Jennifer Sims, Armelle Goubard, Remy Castellano, Noemie Joalland, Emmanuel Scotet, Yves Collette, Emmanuel Valentin, Clement Ghigo, Christine Pasero, Magali Colazet, Jaime Guillen, Carla E. Cano, Aurelien Marabelle, Johann De Bonno, Rene Hoet, Alemseged Truneh, Daniel Olive, Paul Frohna
Summary: Gamma delta T cells, when activated by the humanized monoclonal antibody ICT01, show potent cytotoxicity against various tumor cell types in a targeted manner, with promising antitumor effects and acceptable safety profiles in preclinical studies. ICT01 selectively activates V gamma 9V delta 2 T cells, leading to tumor growth inhibition and prolonged survival in animal models, indicating its potential as a targeted therapy for advanced solid tumors.
SCIENCE TRANSLATIONAL MEDICINE
(2021)
