Article
Oncology
Dan Liu, Xiyue Xu, Yulian Dai, Xuan Zhao, Shunshun Bao, Wen Ma, Li Zha, Shuci Liu, Yuchen Liu, Junnian Zheng, Ming Shi
Summary: This study demonstrates that CAR-T therapy induces activation of the AIM2 inflammasome in macrophages, leading to the release of bioactive IL-1 beta. Additionally, the alpha 1-AR-mediated adrenergic signaling enhances the priming of AIM2 inflammasome, while tumor cell DNA release triggers inflammasome activation. The interaction between CAR-T cells and tumor cells causes a phenotypic switch in macrophages, inhibiting the cytotoxicity of CAR-T cells and T cell proliferation through upregulation of PD-L1 and IDO.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2021)
Article
Oncology
Harrison K. Chinn, Jennifer L. Gardell, Lisa R. Matsumoto, Kevin P. Labadie, Tara N. Mihailovic, Nicole A. P. Lieberman, Amira Davis, Venu G. Pillarisetty, Courtney A. Crane
Summary: This study demonstrates the engineering of human macrophages to conditionally express genes under hypoxic conditions, allowing for localized gene delivery in cancer. The engineered macrophages were able to express therapeutic proteins in a controlled manner, making them ideal vehicles for delivering payloads in hypoxic tissues.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Review
Immunology
Yong Fu, Renhong Tang, Xiaofeng Zhao
Summary: Cytokines play a crucial role in cell communication in the tumor microenvironment, but their production and function are often dysregulated during malignant tumor progression. While cytokine-based therapeutics have shown early success in cancer immunotherapy, their clinical translation has been limited due to their pleiotropic nature, complex biological properties, and poor pharmacokinetics. New engineering approaches have been developed to improve the delivery, targeting, and therapeutic efficacy of cytokines, and this review focuses on the recent progress, competitive landscape, and feasibility of these methods in clinical medicine translation.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Oncology
Mikiya Ishihara, Shigehisa Kitano, Shinichi Kageyama, Yoshihiro Miyahara, Noboru Yamamoto, Hidefumi Kato, Hideyuki Mishima, Hiroyoshi Hattori, Takeru Funakoshi, Takashi Kojima, Tetsuro Sasada, Eiichi Sato, Sachiko Okamoto, Daisuke Tomura, Ikuei Nukaya, Hideto Chono, Junichi Mineno, Muhammad Faris Kairi, Phuong Diem Hoang Nguyen, Yannick Simoni, Alessandra Nardin, Evan Newell, Michael Fehlings, Hiroaki Ikeda, Takashi Watanabe, Hiroshi Shiku
Summary: This study investigated the use of T-cell receptor (TCR)-engineered T cells to treat patients with solid tumors expressing NY-ESO-1. The results showed significant tumor response and some patients experienced early-onset cytokine release syndrome (CRS). One patient developed severe lung injury associated with the TCR-T cell infusion.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Article
Cell Biology
Aslan Mansurov, Abigail Lauterbach, Erica Budina, Aaron T. Alpar, Jeffrey A. Hubbell, Jun Ishihara
Summary: Efforts to achieve therapeutic translation of cytokines for treating diseases such as cancer and autoimmune diseases have been hindered by the unfavorable pharmacokinetic and pharmacodynamic profiles of wild-type cytokines, leading to challenging toxicity profiles and limited therapeutic efficacy. Further research and development in protein-engineering approaches are needed to address these limitations and enhance the therapeutic indices of cytokines for more effective treatment.
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
(2021)
Review
Immunology
Luciano Santollani, K. Dane Wittrup
Summary: Cytokines have shown potential as cancer immunotherapy, but their clinical success has been limited due to narrow therapeutic windows and dose-limiting toxicities. The systemic administration used in most exogenous cytokine therapies does not mimic the localized, regulated deployment of endogenous cytokines. Furthermore, cytokines' ability to stimulate multiple cell types with paradoxical effects poses challenges for their translation into effective therapies. Protein engineering offers strategies to address these limitations and bring exogenous cytokine therapies closer to their endogenous exposure profile, unlocking their full therapeutic potential.
IMMUNOLOGICAL REVIEWS
(2023)
Review
Pharmacology & Pharmacy
Patrick G. Holder, Shion A. Lim, Christine S. Huang, Preeti Sharma, Yavuz S. Dagdas, Beyza Bulutoglu, Jonathan T. Sockolosky
Summary: Cytokines are potent immunoregulatory proteins that play important roles in cancer and have the potential for cancer immunotherapy. However, the use of cytokines as therapeutics has been limited by their complex biology and toxicities. Recent advances in immune checkpoint inhibitors and combination immunotherapies have reinvigorated interest in cytokines as therapeutics.
ADVANCED DRUG DELIVERY REVIEWS
(2022)
Article
Oncology
Karan Kohli, Lu Yao, Theodore Scott Nowicki, Shihong Zhang, Ralph Graeme Black, Brett A. Schroeder, Erik A. Farrar, Jianhong Cao, Heather Sloan, Dawn Stief, Lee D. Cranmer, Michael J. Wagner, Douglas S. Hawkins, Venu G. Pillarisetty, Antoni Ribas, Jean Campbell, Robert H. Pierce, Edward Y. Kim, Robin L. Jones, Stanley R. Riddell, Cassian Yee, Seth M. Pollack
Summary: The study demonstrated that ETC targeting NY-ESO-1 with single-agent cyclophosphamide conditioning was well tolerated in patients with SS and MRCL. IL-15 could induce proliferation and activity in persisting NY-ESO-1-specific T cells even in patients with disease progression following ACT. These results support further evaluation of incorporating IL-15 into ACT trials post-infusion or at the time of progression.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2021)
Article
Pharmacology & Pharmacy
Cesare Di Nitto, Ettore Gilardoni, Jacqueline Mock, Lisa Nadal, Tobias Weiss, Michael Weller, Frauke Seehusen, Chiara Libbra, Emanuele Puca, Dario Neri, Roberto De Luca
Summary: In this study, a novel fusion protein (L19-IFN gamma KRG) is described, which selectively localizes to tumors and regains biological activity upon antigen binding. This fusion protein showed tumor growth inhibition and increased intratumoral concentration of T cells and NK cells in murine cancer models, with a better effect when used in combination with anti-PD-1 therapy.
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)
Review
Cell Biology
Yingjun Peng, Shengyu Fu, Qi Zhao
Summary: This review outlines the potential and applications of IL-15 in cancer immunotherapy, discussing its role in regulating immune cells and providing prospects for future therapeutic designs.
JOURNAL OF LEUKOCYTE BIOLOGY
(2022)
Review
Immunology
Andrew Kent, Natalie V. Longino, Allison Christians, Eduardo Davila
Summary: T cell-based immunotherapies have shown significant anti-tumor effects, providing hope to cancer patients, but durable responses are not universal and immune-mediated toxicity can occur. Understanding the genetic, phenotypic and activation state nuances of T cells is crucial for optimizing therapeutic impact. Researchers are exploring therapeutic strategies targeting specific molecules to enhance anti-tumor T cell activity.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Oncology
Gabrielle Leclercq, Helene Haegel, Alberto Toso, Tina Zimmermann, Luke Green, Nathalie Steinhoff, Johannes Sam, Vesna Pulko, Anneliese Schneider, Anna Maria Giusti, John Challier, Anne Freimoser-Grundschober, Laurent Lariviere, Alex Odermatt, Martin Stern, Pablo Umana, Marina Bacac, Christian Klein
Summary: This study aimed to identify small molecules that can reduce cytokine release while maintaining T cell-mediated tumor killing. By screening a library of FDA-approved kinase inhibitors, mTOR, JAK, and Src kinase inhibitors were found to modulate cytokine release. Further in vitro and in vivo experiments confirmed these findings and supported the evaluation of these inhibitors as a treatment to prevent cytokine release syndrome (CRS).
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Review
Immunology
Suheil Albert Atallah-Yunes, Michael J. Robertson
Summary: Cytokines play a regulatory role in the immune responses to cancer. While they have shown antitumor activity in preclinical models, their success as single therapeutic agents in clinical trials of cancer immunotherapy has been limited. However, combining cytokines with other immune therapeutics and advancements in genetic engineering, synthetic biology, and cellular and immune therapy have revived interest in cytokines as anticancer agents.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
Pietro Ghezzi, Giamila Fantuzzi, Charles A. A. Dinarello
Summary: This Perspective highlights the work of Dr. Daniela Novick on cytokine biology, specifically her identification of soluble receptors and binding proteins for various cytokines using affinity chromatography. Her findings have been crucial in the development of monoclonal antibodies against interferons and cytokines. The Perspective also discusses her recent review on this topic.
FRONTIERS IN IMMUNOLOGY
(2023)
