Article
Multidisciplinary Sciences
Greg M. Allen, Nicholas W. Frankel, Nishith R. Reddy, Hersh K. Bhargava, Maia A. Yoshida, Sierra R. Stark, Megan Purl, Jungmin Lee, Jacqueline L. Yee, Wei Yu, Aileen W. Li, K. Christopher Garcia, Hana El-Samad, Kole T. Roybal, Matthew H. Spitzer, Wendell A. Lim
Summary: In this study, we engineered circuits in CAR T cells to locally induce production of the cytokine IL-2 using tumor-specific synNotch receptors. These circuits enhance CAR T cell infiltration and clearance of immunosuppressive tumors, without causing systemic toxicity. The most effective IL-2 induction circuit acts in an autocrine and TCR- or CAR-independent manner, bypassing key tumor suppression mechanisms.
Article
Chemistry, Multidisciplinary
Jie Zhang, Biao Fan, Guoliang Cao, Wenping Huang, Fuhao Jia, Guangjun Nie, Hai Wang
Summary: This study developed a personalized DC-mimicking nanovaccine for stimulating TAAs-specific T cell populations. By inducing BMDCs maturation and delivering TAAs through nanostructures, the nanoDCs efficiently generated potent antigen-specific T cell responses, leading to inhibition of tumor growth and metastases formation.
ADVANCED MATERIALS
(2022)
Article
Oncology
Mirela Kremenovic, Alfred A. Chan, Bing Feng, Lukas Baeriswyl, Steve Robatel, Thomas Gruber, Li Tang, Delphine J. Lee, Mirjam Schenk
Summary: In this study, a novel BCG lysate was developed and formulated into a thermosensitive hydrogel. The BCG lysate exhibited enhanced antitumor efficacy and promoted a proinflammatory tumor microenvironment in vivo. The underlying mechanisms of BCG lysate-mediated tumor immunity relied on macrophages (M phi) and dendritic cells (DCs). The BCG hydrogel treatment induced systemic immunity, suppressed lung metastases, and improved survival in melanoma-bearing mice. Furthermore, BCG hydrogel treatment enhanced antigen processing and presentation, and increased the frequency of melanoma-reactive CD8(+) T cells. In human melanoma patients, intralesional-BCG treatment was associated with enhanced M1 M phi, mature DCs, antigen processing and presentation, and increased patient survival.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Article
Biology
Fernando Y. Maeda, Jurriaan J. H. van Haaren, David B. Langley, Daniel Christ, Norma W. Andrews, Wenxia Song
Summary: Recognition of antigen by B-cell receptor results in localized plasma membrane permeabilization, triggering PM repair responses involving lysosomal exocytosis to facilitate antigen internalization and presentation. Higher affinity antigens cause more B-cell permeabilization and are efficiently presented to T-cells.
Article
Biotechnology & Applied Microbiology
Yu-Yang Ng, Johan C. K. Tay, Zhendong Li, Junjian Wang, Jiangqing Zhu, Shu Wang
Summary: The study shows that T cells expressing NKG2D-DAP12 CAR have lower cytokine release during tumor cell lysis compared to those expressing the commonly used CD3 zeta activation domain, although there is no difference in mediating in vitro tumor cell lysis between the two CARs. Additionally, both types of CAR-T cells exhibit similar anti-tumor activity in tumor-bearing NSG mice, but NKG2D-CDg CAR-T cells lead to higher cytokine release and mortality due to xenogeneic graft versus host disease compared to NKG2D-DAP12 CAR-T cells. Incorporating the DAP12 activation domain in CAR design may provide a potential clinical advantage in mitigating the risk of cytokine release syndrome.
Review
Chemistry, Multidisciplinary
Heng Dong, Qiang Li, Yu Zhang, Meng Ding, Zhaogang Teng, Yongbin Mou
Summary: Dendritic cell (DC)-based cancer immunotherapy has shown great potential in clinical application. However, traditional DC-mediated immunotherapy faces challenges such as insufficient antigen delivery, inadequate antigen presentation, and high levels of immunosuppression. To overcome these challenges, engineered biomaterials have been utilized to enhance the effects of DC-mediated immunotherapy. This review summarizes the key components that can enhance DC-mediated immunotherapeutic effects, discusses the parameters considered in the design of biomaterials, and reviews recent applications of engineered biomaterials in DC-mediated immunotherapy, including as delivery platforms and modulators of the tumor microenvironment. The review aims to inspire the clinical translation of future DC-mediated cancer immunotherapies.
Review
Immunology
Takumi Kawasaki, Moe Ikegawa, Taro Kawai
Summary: The lungs have an immune defense mechanism that uses various cells to eliminate harmful pathogens and activate T cell immune response. In addition to immune cells, other lung cells also participate in antigen presentation and T cell activation.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Multidisciplinary Sciences
Jiqin Zhang, Yongxian Hu, Jiaxuan Yang, Wei Li, Mingming Zhang, Qingcan Wang, Linjie Zhang, Guoqing Wei, Yue Tian, Kui Zhao, Ang Chen, Binghe Tan, Jiazhen Cui, Deqi Li, Yi Li, Yalei Qi, Dongrui Wang, Yuxuan Wu, Dali Li, Bing Du, Mingyao Liu, He Huang
Summary: A two-in-one approach to generate non-viral, gene-specific targeted CAR-T cells through CRISPR-Cas9 was successfully developed, demonstrating feasibility and efficacy in a preclinical study. An innovative type of anti-CD19 CAR-T cell with PD1 integration showed superior ability to eradicate tumor cells.
Review
Cell Biology
Enrica Marmonti, Jacqueline Oliva-Ramirez, Cara Haymaker
Summary: Dendritic cells (DCs) are crucial in immunology, yet targeting them remains challenging. Understanding and utilizing dendritic cells can lead to new therapeutic strategies in cancer treatment.
Editorial Material
Immunology
Hu Chen, Hongwei Cheng, Xiaoliu Liang, Shundong Cai, Gang Liu
Summary: Although immunotherapy has brought new possibilities for cancer treatment, insufficient immune response limits its effectiveness. The ASPIRE nanovaccine derived from dendritic cells offers a simplified and personalized approach to immunotherapy, potentially revolutionizing cancer treatment.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Immunology
Christophe Macri, Devi Jenika, Cassandra Ouslinis, Justine D. Mintern
Summary: Dendritic cells (DCs) are specialized antigen-presenting cells that play a critical role in adaptive immunity. Targeting antigen directly to DCs is a selective vaccination strategy that takes advantage of the antigen uptake and presentation functions of DC subsets. This review focuses on DC-targeted vaccination strategies aimed at inducing effective cross-presentation for CD8+ T cell immunity. Receptors highly expressed by mouse and human cDCs, such as DEC205, Clec9A, and XCR1, are explored. The outcomes of DC-targeted vaccination in mouse models and human clinical trials are discussed, highlighting its potential for the prevention and treatment of tumors and infectious diseases.
SEMINARS IN IMMUNOLOGY
(2023)
Review
Biochemical Research Methods
Cuilin Zhang, Qiuyu Zhuang, Jingfeng Liu, Xiaolong Liu
Summary: Synthetic biology is an interdisciplinary research area that uses engineering principles to design and construct biological systems for practical applications. Chimeric antigen receptor (CAR) T cells, as one of the most successful clinical applications of synthetic biology, have shown tremendous success in treating blood malignancies. However, there are still limitations to CAR T cell therapy, hence the need for innovative CAR design becomes urgent.
ACS SYNTHETIC BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Mariangela O. Silva, Bianca S. Almeida, Natiely S. Sales, Mariana O. Diniz, Luana R. M. M. Aps, Karine B. Rodrigues, Jamile R. Silva, Ana C. R. Moreno, Bruna F. M. M. Porchia, Fernando B. Sulczewski, Silvia B. Boscardin, Luis C. S. Ferreira
Summary: The delivery of HPV tumor antigens to DCs, particularly via the DEC205 surface receptor, is a promising therapeutic approach, providing new opportunities for the development of alternative immunotherapies for patients with HPV-associated tumors.
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
(2021)
Article
Nanoscience & Nanotechnology
Yuanyuan Zhang, Tong Ge, Meijuan Huang, Yun Qin, Tianjiao Liu, Wei Mu, Gaoxiang Wang, Lijun Jiang, Tongjuan Li, Lei Zhao, Jue Wang
Summary: This study investigated the potential of CAR antigen-modified extracellular vesicles (EVs) to enhance the effectiveness of CAR-T cell therapy. The results showed that CD19 antigen-expressing EVs specifically and dose-dependently activated CAR-T cells, leading to selective expansion and cytokine secretion. Furthermore, the CD19 EVs increased the anti-tumor activity of CAR-T cells. In vivo experiments demonstrated that CD19 EVs promoted the functional persistence of CAR-T cells. Overall, these findings suggest that antigen-expressing EVs can be utilized as a boost to improve the efficacy of CAR-T cell therapy.
INTERNATIONAL JOURNAL OF NANOMEDICINE
(2023)
Article
Multidisciplinary Sciences
Frank J. Lowery, Sri Krishna, Rami Yossef, Neilesh B. Parikh, Praveen D. Chatani, Nikolaos Zacharakis, Maria R. Parkhurst, Noam Levin, Sivasish Sindiri, Abraham Sachs, Kyle J. Hitscherich, Zhiya Yu, Nolan R. Vale, Yong-Chen Lu, Zhili Zheng, Li Jia, Jared J. Gartner, Victoria K. Hill, Amy R. Copeland, Shirley K. Nah, Robert Masi, Billel Gasmi, Scott Kivitz, Biman C. Paria, Maria Florentin, Sanghyun P. Kim, Ken-ichi Hanada, Yong F. Li, Lien T. Ngo, Satyajit Ray, Mackenzie L. Shindorf, Shoshana T. Levi, Ryan Shepherd, Chris Toy, Anup Y. Parikh, Todd D. Prickett, Michael C. Kelly, Rachel Beyer, Stephanie L. Goff, James C. Yang, Paul F. Robbins, Steven A. Rosenberg
Summary: Mapping TCRs from metastatic tumors to single-cell transcriptomes identified tumor-specific expanded neoantigen-specific TILs with dysfunctional phenotypes. Prospectively testing signature-derived clonotypes demonstrated TCR recognition of tumor antigens, suggesting a common metastatic TIL exhaustion program. NeoTCR signatures enable successful TCR prediction for cancer immunotherapy based on TIL transcriptomic states.
