Article
Oncology
Emiliano Roselli, Justin C. Boucher, Gongbo Li, Hiroshi Kotani, Kristen Spitler, Kayla Reid, Estelle Cervantes, Yannick Bulliard, Nhan Tu, Sae Bom Lee, Bin Yu, Frederick L. Locke, Marco L. Davila
Summary: The study demonstrates that combining 4-1BB with an optimized form of CD28 for co-stimulation is an effective way to enhance CAR T cell function. Both mono-specific and bi-specific versions of this design show improved expansion, persistence, and resistance to exhaustion in vitro and in vivo.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2021)
Article
Immunology
Leena Halim, Kushal K. Das, Daniel Larcombe-Young, Adam Ajina, Andrea Candelli, Reuben Benjamin, Richard Dillon, David M. Davies, John Maher
Summary: This study demonstrates the enhanced anti-tumor activity of CAR T-cells through dual co-stimulation provided by a parallel CAR architecture. CD19-specific CAR and pCAR T-cells showed broad binding ability and avidity for CD19-expressing tumor cells. Each pCAR showed significant improvement in tumor re-stimulation potential and therapeutic efficacy compared to unmodified or mutated CARs.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Hematology
Sarah J. Nagle, Catherine Murphree, Philipp W. Raess, Levanto Schachter, Andy Chen, Brandon Hayes-Lattin, Eneida Nemecek, Richard T. Maziarz
Summary: CAR T-cell therapy is effective in treating patients with R/R DLBCL, but it is associated with significant prolonged hematologic toxicity (PHT) that can affect patients' survival rates. Risk factors associated with PHT include CRS, the use of tocilizumab or steroids, peak levels of ferritin and C-reactive protein. More research is needed to further investigate PHT and establish management standards.
AMERICAN JOURNAL OF HEMATOLOGY
(2021)
Article
Immunology
Yannick D. Muller, Duy P. Nguyen, Leonardo M. R. Ferreira, Patrick Ho, Caroline Raffin, Roxxana Valeria Beltran Valencia, Zion Congrave-Wilson, Theodore L. Roth, Justin Eyquem, Frederic Van Gool, Alexander Marson, Laurent Perez, James A. Wells, Jeffrey A. Bluestone, Qizhi Tang
Summary: This study revealed a fundamental difference between CD28-TMD and CD8-TMD, indicating that CD28-TMD can modulate CAR T-cell activities by engaging endogenous partners.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Oncology
Kathryn M. Cappell, James N. Kochenderfer
Summary: CAR T cell therapies targeting haematological malignancies show promising efficacy, with CD28- and 4-1BB-derived costimulatory domains demonstrating potentially different cellular and clinical effects. Further research is needed to compare their effectiveness and toxicity profiles.
NATURE REVIEWS CLINICAL ONCOLOGY
(2021)
Review
Oncology
Lijuan Wu, Junchao Chen, Ruifen Cai, Xinrui Wang, Yixiao Liu, Qingshan Zheng, Lujin Li
Summary: This study quantified the differences in the efficacy and safety of different stimulation domains of anti-CD19 chimeric antigen receptor (CAR) T therapy for B-cell acute lymphoblastic leukemia (B-ALL). The results showed that anti-CD19 CAR T-cells with the 4-1BB co-stimulatory domain had longer overall survival and progression-free survival compared to those with the CD28 co-stimulatory domain. Furthermore, the CD28 co-stimulatory domain showed a higher incidence of neurotoxic adverse effects. These findings provide important quantitative information for comparing the different co-stimulatory domains of anti-CD19 CAR T-cells for treating B-ALL.
Article
Immunology
Yunlong Zhao, Christine Caron, Ya-Yuan Chan, Calvin K. Lee, Xiaozhen Xu, Jibin Zhang, Takeya Masubuchi, Chuan Wu, Jack D. Bui, Enfu Hui
Summary: In this study, it was discovered that B7 ligands on CD8+ T cells interact with CD28 in a cis configuration at membrane invaginations of the immunological synapse, which is driven by phosphoinositide-3-kinase (PI3K) and sorting-nexin-9 (SNX9) mediated membrane remodeling. Cis-B7:CD28 interactions activate CD28 signaling through protein kinase C theta (PKCq), promoting CD8+ T cell survival, migration, and cytokine production.
Review
Oncology
Wenjing Luo, Chenggong Li, Yinqiang Zhang, Mengyi Du, Haiming Kou, Cong Lu, Heng Mei, Yu Hu
Summary: This review systematically analyzes the hematologic toxicity in hematologic malignancies treated with CAR-T cell therapy. The most common side effect is hematological toxicity, with neutropenia, thrombocytopenia and anemia being the most common adverse events. Younger patients, those with more treatment lines, and patients with CD19-positive malignancies are more likely to experience hematological toxicity.
Article
Biotechnology & Applied Microbiology
Fan Fei, Liang Rong, Nan Jiang, Alan S. Wayne, Jianming Xie
Summary: In this study, an anti-HLA-DR inhibitory CAR (iCAR) was developed to effectively suppress NK cell activation against HLA-DR-expressing cells. Dual CAR-NK cells, which co-express the anti-CD19 or CD33 activating CAR and the anti-HLA-DR iCAR, were found to preferentially target HLA-DR-negative cells over HLA-DR-positive cells in vitro. The HLA-DR-mediated inhibition was positively correlated with both iCAR and HLA-DR densities. HLA-DR-positive cells were resistant to dual CAR-NK cell-mediated killing in a xenograft mouse model, confirming the potential of this approach to enhance CAR-NK and CAR-T cell specificity against malignancies with HLA-DR loss.
Article
Immunology
Shouheng Lin, Lin Cheng, Wei Ye, Shanglin Li, Diwei Zheng, Le Qin, Qiting Wu, Youguo Long, Simiao Lin, Suna Wang, Guohua Huang, Peng Li, Yao Yao, Xiaofang Sun
Summary: The newly developed CTLA4-CAR T cells convert negative signals to positive signals, enhancing cytokine secretion and cytotoxicity to tumor cells in vitro and xenograft models. In preclinical models, CTLA4-CAR T cells exhibit toxicity to MDSCs in tumors without severe GVHD and CRS signs.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Oncology
Ana Textor, Laura Grunewald, Kathleen Anders, Anika Klaus, Silke Schwiebert, Annika Winkler, Maria Stecklum, Jana Rolff, Anton G. Henssen, Uta E. Hoepken, Angelika Eggert, Johannes H. Schulte, Michael C. Jensen, Thomas Blankenstein, Annette Kuenkele
Summary: Efficient trafficking and survival of CAR T cells in the tumor microenvironment are crucial for solid tumor attack, and using murine T cells to generate CAR T cells can help predict and select promising clinical candidates, especially for CAR T cells with CD28 co-stimulatory domain showing superior performance in solid tumor attack.
Review
Hematology
Matthew Ho, Saurabh Zanwar, Jonas Paludo
Summary: The success of CAR-T therapy in hematologic malignancies has achieved the goal of using the immune system to fight cancer personalizedly. Second generation CAR incorporating co-stimulatory molecules has overcome some limitations and resulted in effective products. Many second-generation CAR-T products have been approved for the treatment of relapsed/refractory hematologic malignancies including MM, NHL, and acute lymphoblastic leukemia. However, challenges remain in optimizing manufacturing, timely access, limiting toxicities, and improving sustainability of CAR-T therapy responses.
EUROPEAN JOURNAL OF HAEMATOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Chen-Lu Geng, Jun-Yi Chen, Tian -Yu Song, Jae Hyung Jung, Min Long, Min -Fang Song, Tong Ji, Byung Soh Min, Jin Gu Lee, Bo Peng, Yi-Sheng Pu, Hong-Jie Fan, Piliang Hao, Qi Zhou, Eui-Cheol Shin, Yong Cang
Summary: CD28 loss limits the clinical benefits of PD-1 immunotherapy in cancer patients. We found that using lenalidomide can reinstate the anti-tumor activity of CD28-deficient CD8+ T cells and enhance the efficacy of PD-1 immunotherapy.
CELL CHEMICAL BIOLOGY
(2022)
Article
Immunology
Zilong Guo, Yirui Zhang, Mingpeng Fu, Liang Zhao, Zhen Wang, Zhuoshuo Xu, Huifen Zhu, Xiaoli Lan, Guanxin Shen, Yong He, Ping Lei
Summary: The transferrin receptor (TfR) is being evaluated as an alternative target for CAR T cell therapy, showing potent cytotoxic effects against hematological malignancies. This suggests TfR could potentially broaden and enhance the therapeutic efficacy of CAR T cells, making it a promising universal target for further research.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Cardiac & Cardiovascular Systems
Matthias Totzeck, Lars Michel, Yi Lin, Joerg Herrmann, Tienush Rassaf
Summary: Chimeric antigen receptor (CAR)-T cell therapy is a revolutionary advance in cancer treatment, but it can lead to cytokine release syndrome and cardiovascular events.
EUROPEAN HEART JOURNAL
(2022)
Meeting Abstract
Oncology
Scott H. Olejniczak, Gaspare La Rocca, Megan Radler, Craig B. Thompson
Article
Multidisciplinary Sciences
Gaspare La Rocca, Scott H. Olejniczak, Alvaro J. Gonzalez, Daniel Briskin, Joana A. Vidigal, Lee Spraggon, Raymond G. DeMatteo, Megan R. Radler, Tullia Lindsten, Andrea Ventura, Thomas Tuschl, Christina S. Leslie, Craig B. Thompson
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2015)
Article
Biochemistry & Molecular Biology
Scott H. Olejniczak, Gaspare La Rocca, Megan R. Radler, Shawn M. Egan, Qing Xiang, Ralph Garippa, Craig B. Thompson
MOLECULAR AND CELLULAR BIOLOGY
(2016)
Article
Hematology
Seerat Elahi, Shawn M. Egan, G. Aaron Holling, Rachel L. Kandefer, Michael J. Nemeth, Scott H. Olejniczak
EXPERIMENTAL HEMATOLOGY
(2018)
Article
Chemistry, Multidisciplinary
Mackenzie M. Honikel, Chi-En Lin, Brittney A. Cardinell, Jeffrey T. LaBelle, Andrew D. Penman
Article
Oncology
Guanxi Qiao, Mark J. Bucsek, Nicolette M. Winder, Minhui Chen, Thejaswini Giridharan, Scott H. Olejniczak, Bonnie L. Hylander, Elizabeth A. Repasky
CANCER IMMUNOLOGY IMMUNOTHERAPY
(2019)
Article
Biochemistry & Molecular Biology
Tatiana Londono Gentile, Chao Lu, Peter M. Lodato, Sarah Tse, Scott H. Olejniczak, Eric S. Witze, Craig B. Thompson, Kathryn E. Wellen
MOLECULAR AND CELLULAR BIOLOGY
(2013)
Article
Oncology
Jennifer Blickwedehl, Scott Olejniczak, Ryan Cummings, Nilofar Sarvaiya, Ana Mantilla, Asher Chanan-Khan, Tej K. Pandita, Marion Schmidt, Craig B. Thompson, Naveen Bangia
MOLECULAR CANCER RESEARCH
(2012)
Article
Multidisciplinary Sciences
Scott H. Olejniczak, Gaspare La Rocca, Joshua J. Gruber, Craig B. Thompson
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2013)
Article
Cell & Tissue Engineering
Seerat Elahi, G. Aaron Holling, Aimee B. Stablewski, Scott H. Olejniczak
STEM CELL RESEARCH
(2020)
Article
Cell Biology
Adam Utley, Colin Chavel, Shivana Lightman, G. Aaron Holling, James Cooper, Peng Peng, Wensheng Liu, Benjamin G. Barwick, Catherine M. Gavile, Orla Maguire, Megan Murray-Dupuis, Cheryl Rozanski, Martha S. Jordan, Taku Kambayashi, Scott H. Olejniczak, Lawrence H. Boise, Kelvin P. Lee
Article
Immunology
Shivana M. Lightman, Jennifer L. Peresie, Louise M. Carlson, G. Aaron Holling, Mackenzie M. Honikel, Colin A. Chavel, Michael J. Nemeth, Scott H. Olejniczak, Kelvin P. Lee
Summary: Humoral immunity is crucial for protecting the body against pathogens, and long-term protective immunity relies on the continual production of neutralizing antibodies by long-lived plasma cells (LLPCs). Recent research has shown that the immunosuppressive enzyme IDO1 plays a key role in sustaining antibody responses and LLPC survival.