Editorial Material
Biochemistry & Molecular Biology
Johannes B. Huppa, Gerhard J. Schuetz
Summary: T-cell antigen recognition is affected by tensile forces, which reduce the lifetime of stable stimulatory TCR-pMHC interactions more than less stable non-stimulatory TCR-pMHC interactions. The authors propose that forces hinder rather than enhance T-cell antigen discrimination, which is facilitated by force-shielding within the immunological synapse through cell adhesion via CD2/CD58 and LFA-1/ICAM-1.
Article
Oncology
Karen Kai-Lin Fang, Jongbok Lee, Ismat Khatri, Yoosu Na, Li Zhang
Summary: The use of allogeneic CAR4-DNTs as adoptive cell therapy for T-cell malignancies is effective. CAR4-DNTs can effectively target T-ALL and PTCL and have superior cytotoxicity compared to empty-vector transduced DNTs.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2023)
Article
Oncology
Catherine M. Ade, Matthew J. Sporn, Sudipto Das, Zhiya Yu, Ken-ichi Hanada, Yue A. Qi, Tapan Maity, Xu Zhang, Udayan Guha, Thorkell Andresson, James C. Yang
Summary: This article introduces a method of using mass spectrometry to identify common tumor-specific neoepitopes derived from mutated oncogenes, and develop TCRs based on these data. The results of the study show that this method successfully identified precise neoepitopes derived from KRAS, EGFR, BRAF, and PIK3CA presented by HLA-A*03:01 and/or HLA-A*11:01 across multiple biological replicates.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2023)
Review
Immunology
Qijie Zhao, Yu Jiang, Shixin Xiang, Parham Jabbarzadeh Kaboli, Jing Shen, Yueshui Zhao, Xu Wu, Fukuan Du, Mingxing Li, Chi Hin Cho, Jing Li, Qinglian Wen, Tao Liu, Tao Yi, Zhangang Xiao
Summary: This review provides insights into the role of engineered T-cell receptors (TCRs) in immunotherapy and discusses novel approaches to enhance anticancer immune system. It also highlights the importance of safety in genetically modified T cells and explores different strategies such as ImmTAC, HSV-TK, and inducible caspase-9 in cancer immunotherapy. Clinical trials related to TCR-T cell therapy and monoclonal antibodies designed to overcome immunosuppression are also discussed, along with recent advances in understanding TCRs and new approaches to detect antigens and drive effective T cell response.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Oncology
Talar Tokatlian, Grace E. Asuelime, Jee-Young Mock, Breanna DiAndreth, Shruti Sharma, Dora Toledo Warshaviak, Mark E. Daris, Kristian Bolanos, Breanna L. Luna, Martin S. Naradikian, Kiran Deshmukh, Agnes E. Hamburger, Alexander Kamb
Summary: This study developed a dual-receptor system that can target mesothelin expressed in both tumor and normal tissues, reducing the risk of serious inflammation caused by the treatment.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Article
Engineering, Biomedical
Alex G. Hamilton, Kelsey L. Swingle, Ryann A. Joseph, David Mai, Ningqiang Gong, Margaret M. Billingsley, Mohamad-Gabriel Alameh, Drew Weissman, Neil C. Sheppard, Carl H. June, Michael J. Mitchell
Summary: A ionizable lipid nanoparticle (LNP) platform was developed for simultaneous therapeutic gene expression and RNA interference (RNAi)-mediated transient gene knockdown in T cells. Co-encapsulating mRNA and siRNA resulted in improved expression and knockdown characteristics compared to delivering either cargo alone. This platform was used to deliver CAR mRNA and siRNA targeting PD-1 to primary human T cells ex vivo, leading to strong CAR expression and PD-1 knockdown without apparent changes to overall T cell activation state. This delivery platform shows great promise for transient immune gene modulation in immunoengineering applications, including improved cancer immunotherapies.
ADVANCED HEALTHCARE MATERIALS
(2023)
Article
Multidisciplinary Sciences
Verena Turco, Kira Pfleiderer, Jessica Hunger, Natalie K. Horvat, Kianush Karimian-Jazi, Katharina Schregel, Manuel Fischer, Gianluca Brugnara, Kristine Jaehne, Volker Sturm, Yannik Streibel, Duy Nguyen, Sandro Altamura, Dennis A. Agardy, Shreya S. Soni, Abdulrahman Alsasa, Theresa Bunse, Matthias Schlesner, Martina U. Muckenthaler, Ralph Weissleder, Wolfgang Wick, Sabine Heiland, Philipp Vollmuth, Martin Bendszus, Christopher B. Rodell, Michael O. Breckwoldt, Michael Platten
Summary: Glioblastoma, the most aggressive brain tumor type, can be treated by reprogramming myeloid cells using CDNP-R848 nanoparticles. CDNP-R848 induces tumor regression by targeting blood-borne macrophages independently of adaptive immunity.
NATURE COMMUNICATIONS
(2023)
Review
Immunology
Pilar Martin, Rafael Blanco-Dominguez, Raquel Sanchez-Diaz
Summary: Over the past decade, T cell-based approaches using immunomodulatory receptors like PD-1 and CTLA-4 have shown significant improvement in cancer treatments. However, their potential roles in autoimmune and cardiovascular diseases remain largely unexplored. CD69 receptor, known to be expressed in autoimmune and cardiovascular diseases as well as cancer, has emerged as a promising modulator, but inhibiting these receptors may lead to loss of immunological tolerance. Further research on the functions of different immunomodulatory receptors is crucial for developing new therapies with fewer side effects.
CELLULAR & MOLECULAR IMMUNOLOGY
(2021)
Article
Oncology
Oezcan Cinar, Bernadette Brzezicha, Corinna Grunert, Peter Michael Kloetzel, Christin Beier, Caroline Anna Peuker, Ulrich Keller, Antonio Pezzutto, Antonia Busse
Summary: Adoptive transfer of T cells engineered to target specific mutations in B-cell lymphoma has shown promising results in preclinical studies, suggesting a potential novel treatment strategy with high tumor specificity. The engineered T cells exhibited mutation-specific reactivity and therapeutic efficacy in killing lymphoma cell lines carrying the targeted mutation. Initial safety screening also indicated a lack of off-target reactivity, supporting the feasibility and safety of using mutation-specific TCRs for precision therapy in a subgroup of B-cell malignancies.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2021)
Article
Multidisciplinary Sciences
Shuang Qiu, Zihan Zhao, Mengyao Wu, Qi Xue, Yang Yang, Shian Ouyang, Wannan Li, Lingyu Zhong, Wenjian Wang, Rong Yang, Peng Wu, Jie P. Li
Summary: FucoID is a technique that allows us to study cell-cell interactions and investigate unknown cellular interactions. This technology provides a molecular resolution approach to gain a better understanding of the mechanisms underlying cell-cell interactions.
Article
Engineering, Biomedical
Julian F. Ashby, Julien Schmidt, K. C. Neelima, Armand Kurum, Caroline Koch, Alexandre Harari, Li Tang, Sam H. Au
Summary: This study presents a novel microfluidic approach based on fluid shear stress to identify and recover highly potent T cell clones through probing cellular avidity. The method demonstrates efficient and rapid recovery of high-purity T cells from mixed populations, and markers of cytotoxicity, activation, and avidity persist upon exposure to fresh tumor cells.
ADVANCED HEALTHCARE MATERIALS
(2022)
Review
Immunology
Matthew Bell, Stephen Gottschalk
Summary: CAR T cell therapy is effective for hematological malignancies, but there is a need to improve its efficacy for solid tumors and brain tumors. Several approaches are being pursued to enhance the antitumor activity of CAR T cells, including augmenting signal 3 of T cell activation and improving the function of CAR T cells in the tumor microenvironment.
FRONTIERS IN IMMUNOLOGY
(2021)
Correction
Oncology
C. Xiong, L. Huang, H. Kou
Summary: HLA-A*11:01-restricted epitopes of HPV16 E6/E7 and corresponding T cell receptors (TCRs) were identified in this study. The specific TCRs showed high functional avidity and were able to specifically recognize and kill tumor cells expressing these epitopes. Furthermore, these TCR-T cells also demonstrated activity against patient-derived organoids. These findings may provide a new strategy for HPV-related cancer immunotherapy in HLA-A*11:01-positive patients.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Review
Biotechnology & Applied Microbiology
Lingzhu Zhao, Guoqing Zhao, Jinteng Feng, Zheng Zhang, Jiayu Zhang, Hui Guo, Min Lin
Summary: T cell immune responses play a crucial role in both physiological and pathological processes. Mechanosensitive receptors in the microenvironment are found to regulate various T cell immune responses, including activation, cytokine production, metabolism, proliferation, and migration, in addition to biochemical cues. These mechanical cues are converted into biochemical signals by force-sensitive receptors in the immune synapse, a phenomenon widely accepted in the emerging field of immunomechanobiology. This review provides insights into immunomechanobiology, specifically focusing on the binding and triggering of mechanosensitive receptors and resulting T cell immune responses.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2023)
Article
Oncology
Sharmila Raghunandan, Melinda Pauly, William G. Blum, Muna Qayed, Madhav Dhodapkar, Mohamed Elkhalifa, Benjamin Watkins, Michelle Schoettler, Edwin Horwitz, Suhag Parikh, Shanmuganathan Chandrakasan, Kathryn Leung, Elyse Bryson, Laura Deeb, Jonathan L. Kaufman, Diana Worthington-White, Adina Alazraki, Jordan M. Schecter, Deepu Madduri, Carolyn C. Jackson, Enrique Zudaire, Agne Taraseviciute-Morris, Alexander Babich, Tonia Nesheiwat, Martin Vogel, Nikoletta Lendvai, Lida Pacaud, Kirsten M. Williams
Summary: Plasmablastic lymphoma (PBL) is a rare subtype of aggressive large B-cell lymphoma that has a poor prognosis. Treatment options are limited and new approaches are needed. This case report highlights the successful use of chimeric antigen receptor T-cell (CAR-T) therapy targeting B-cell maturation antigen (BCMA) in a patient with refractory PBL, resulting in a complete remission without severe adverse effects. This supports the consideration of immunotherapy as a potential treatment option for refractory PBL.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2023)