Review
Immunology
Veronica Ramos-Mejia, Jose Arellano-Galindo, Juan Manuel Mejia-Arangure, Mario Ernesto Cruz-Munoz
Summary: NK cells, as unique immune cells, have the ability to recognize and eliminate transformed hematopoietic cells without prior sensitization or expansion of specific clones. Research on NK cells has made significant progress in understanding their role and characteristics. Not only do they act as effectors against specific pathogens, but they also regulate immune responses and play a crucial role in the design of strategies for cancer immunotherapy.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Pharmacology & Pharmacy
Jesus Paez-Mayorga, Izeia Lukin, Dwaine Emerich, Paul de Vos, Gorka Orive, Alessandro Grattoni
Summary: Beta cell replacement is an attractive alternative for type 1 diabetes management. This review focuses on micro- and macroencapsulation technologies for beta cell transplantation, and addresses challenges such as graft hypoxia and donor shortage.
TRENDS IN PHARMACOLOGICAL SCIENCES
(2022)
Article
Chemistry, Multidisciplinary
M. Tommy Gambles, Jiyuan Yang, Jindrich Kopecek
Summary: The concept of multi-targeted immunotherapeutic systems has revolutionized cancer immunotherapy by engaging the patient's immune system in various ways. The outcomes range from recruiting and activating immune cells upon recognizing cancer cells, to implementing a multi-pronged immune checkpoint blockade strategy, or achieving direct cancer cell death through engaging multiple cell surface receptors. This review focuses on the application of multi-specific immunotherapeutics for B cell malignancies, outlining diverse strategies, summarizing B cell receptor antigen targeting approaches, and discussing the challenges and future prospects of the field.
JOURNAL OF CONTROLLED RELEASE
(2023)
Review
Immunology
Kevin J. J. Lopez, Arthur A. A. Cross-Najafi, Kristine Farag, Benjamin Obando, Deepthi Thadasina, Abdulkadir Isidan, Yujin Park, Wenjun Zhang, Burcin Ekser, Ping Li
Summary: Eliminating major xenoantigens has reduced hyperacute xenograft rejection, but acute rejection remains a challenge in xenotransplantation. NK cells play a role in both cytotoxicity against xenogeneic cells and affecting other immune cells through cytokine secretion. The regulation of NK cell activating and inhibitory receptors is crucial in determining the NK cell response. Inhibition of NK cell activity can protect xenografts. Recent advancements in genetic modifications of porcine xenografts have shown promise in reducing NK cell-mediated rejection. Future research on NK cell tolerance in pregnancy and NK cell evasion in viral infection can further promote xenograft acceptance.
FRONTIERS IN IMMUNOLOGY
(2022)
Letter
Oncology
Ruihao Huang, Qin Wen, Xi Zhang
Summary: CAR-NK cell therapy has the advantages of low side effects and cost. However, limited antitumor effects and proliferative capacity hinder its clinical outcomes. Recent progress in engineering, target design, and combination therapy has been made for CAR-NK cell therapy, especially in treating relapsed or refractory hematological malignancies like acute myeloid leukemia and multiple myeloma. This correspondence provides a summary of the preclinical and clinical updates of universal CAR-NK cell therapy reported at the ASH 2022 annual meeting.
JOURNAL OF HEMATOLOGY & ONCOLOGY
(2023)
Review
Immunology
Ayda Baghery Saghchy Khorasani, Amir-Mohammad Yousefi, Davood Bashash
Summary: CAR NK cells have attracted attention as a viable alternative to CAR T cells due to their MHC-independency, shorter life expectancy, potential for off-the-shelf immune product creation, and potent antitumor properties. This article provides an updated review of the differences between CAR T and CAR NK cells, current enhancements in CAR NK design, sources for collecting NK cells, and strategies for transducing CARs to NK cells.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2022)
Review
Pharmacology & Pharmacy
Shuhang Wang, Kun Chen, Yale Jiang, Guo Zhao, Caie Wang, Hong Fang, Qiyu Tang, Chao Sun, Liang Zhang, Haiyang Wu, Li-Feng Zhang, Ning Li
Summary: Natural killer (NK) cell therapy is emerging as a promising cancer treatment that utilizes innate cytotoxic lymphocytes with germline-encoded receptors to kill cancer cells, virus-infected cells, and other stressed cells. NK cells have the advantage of being safe for allogeneic applications and can be used as off-the-shelf cells, overcoming the limitations of autologous cell therapy. However, NK cells have a shorter in vivo persistence compared to T cells, but they have a reservoir of innate immune receptors and can utilize antibody guidance for target recognition.
DRUG DISCOVERY TODAY
(2023)
Review
Oncology
Berkha Rani, James J. Ignatz-Hoover, Priyanka S. Rana, James J. Driscoll
Summary: Urothelial cell carcinoma (UCC) is a common and difficult-to-treat cancer, especially in the United States where it affects more men than women. While early-stage cases have better prognosis, drug resistance and distant metastasis lead to shorter overall survival. Recent advancements in immune therapies have shown promise in improving patient outcomes, but further research is needed to develop novel strategies to overcome drug resistance and improve patient prognosis.
Review
Oncology
Karen Kai-Lin Fang, Jong Bok Lee, Li Zhang
Summary: T-cell malignancies are aggressive and have poor prognoses, but adoptive cell therapy has shown promise as a new treatment option. Overcoming challenges, such as difficulties in applying this therapy to T-cell malignancies, is a focus of research. This review provides an overview of recent progress in adoptive cell therapy for T-cell malignancies, discussing the benefits and drawbacks of different therapy types and emphasizing the potential advantages and current applications of innate immune cell-based approaches.
Review
Immunology
Xinyi Xiao, Yazhuo Wang, Zhengbang Zou, Yufei Yang, Xinyu Wang, Xin Xin, Sanfang Tu, Yuhua Li
Summary: Chimeric antigen receptor (CAR) T cell therapy has revolutionized the treatment of hematologic malignancies, but there are limitations such as resistance and relapse. In this review, we summarize rational combined modality treatments to enhance the effectiveness of CAR T cell therapy.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Hematology
Aimee Merino, Joseph Maakaron, Veronika Bachanova
Summary: Natural Killer (NK) cells show promise in treating hematologic malignancies. Adoptively transferred allogeneic NK cells have demonstrated safety and minimal risk of complications. Unlike genetically altered T cells, HLA mis-matched NK cells can be used without the risk of graft vs host disease (GVHD), making them ideal for off-the-shelf products. Enhancing NK cell targeting and function in the tumor microenvironment is crucial for the future of NK cell therapy.
Review
Oncology
Junji Tanaka
Summary: CAR-NK cells, with potent anti-leukemia/lymphoma effects and better proliferative capacity, have shown promise as an off-the-shelf allogeneic cellular therapy for overcoming intractable hematological malignancies. The safety and efficacy of CAR-NK cells, particularly in HLA-mismatched allogeneic cord blood-derived CD19 CAR-NK cell therapy for CD19-positive hematological malignancies, have been reported but the durability of clinical effects remains to be clarified.
HEMATOLOGICAL ONCOLOGY
(2021)
Review
Immunology
Jiawen Huang, Xiaobing Huang, Juan Huang
Summary: CAR-T cell therapy has revolutionized cellular immunotherapy against cancers, especially hematological malignancies. However, further research is needed to expand its use against other types of hematological malignancies. Treatment failure, CAR antigen loss, immune evasion, and adverse effects are the major obstacles in CAR-T cell therapy. Recent advancements have focused on enhancing efficacy and reducing toxicity associated with CAR-T cell therapy.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Immunology
Mubin Tarannum, Rizwan Romee, Roman M. Shapiro
Summary: This article summarizes the key challenges and innovative strategies in the clinical application of natural killer cell research.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Immunology
Massimo Fantini, Philip Martin Arlen, Kwong Yok Tsang
Summary: Natural killer (NK) cells are important components of the innate immune system that can recognize and suppress the proliferation of cancer cells. Strategies such as boosting NK cells with modulatory cytokines, adoptive NK cell therapy, and the combination of engineered NK cells with monoclonal antibodies (mAbs) that mediate antibody-dependent cell-mediated cytotoxicity (ADCC) have been developed to enhance the antitumor activity of NK cells. The combination of engineered NK cells with mAbs with higher affinity for CD16 expressed on NK cells shows promise in providing more effective and higher-quality treatments for cancer patients.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Hematology
Lucie M. Turcotte, Qing Cao, Sarah A. Cooley, Julie Curtsinger, Shernan G. Holtan, Xianghua Luo, Ashely Yingst, Daniel J. Weisdorf, Bruce R. Blazar, Jeffrey S. Miller, John E. Wagner, Michael R. Verneris
BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
(2019)
Article
Immunology
Tijana Martinov, Linnea A. Swanson, Elise R. Breed, Christopher G. Tucker, Alexander J. Dwyer, Jenna K. Johnson, Jason S. Mitchell, Nathanael L. Sahli, Joseph C. Wilson, Lovejot M. Singh, Kristin A. Hogquist, Justin A. Spanier, Brian T. Fife
JOURNAL OF IMMUNOLOGY
(2019)
Article
Oncology
Upasana Sunil Arvindam, Paulien M. M. van Hauten, Dawn Schirm, Nicolaas Schaap, Willemijn Hobo, Bruce R. Blazar, Daniel A. Vallera, Harry Dolstra, Martin Felices, Jeffrey S. Miller
Summary: The development of a CLEC12A TriKE molecule targeting AML blasts and LSCs, which activates NK cells and drives NK cell priming while sparing healthy cells, highlights the potential clinical efficacy for the treatment of AML.
Article
Biochemistry & Molecular Biology
Jeffrey S. Miller, Zachary B. Davis, Erika Helgeson, Cavan Reilly, Ann Thorkelson, Jodi Anderson, Noemia S. Lima, Siri Jorstad, Geoffrey T. Hart, John H. Lee, Jeffrey T. Safrit, Hing Wong, Sarah Cooley, Lavina Gharu, Hyunsoo Chung, Patrick Soon-Shiong, Curtis Dobrowolski, Courtney Fletcher, Jonathan Karn, Daniel C. Douek, Timothy W. Schacker
Summary: N-803 is a safe and potential treatment for reducing virus reservoirs in people living with HIV by activating latent virus and enhancing immune cell function.
Article
Health Care Sciences & Services
Riwaaj Lamsal, Jenna K. Johnson, Mehdijaffer Mulla, Jordan Marmet, Arif Somani
Summary: This study improves the documentation of rapid response events by creating a standardized document template, and the results show a significant improvement in the documentation of key elements after using the template.
JOURNAL FOR HEALTHCARE QUALITY
(2022)
Article
Oncology
Heather H. Nelson, Emma Contestabile, De Von Hunter-Schlichting, Devin Koestler, Michael Pawlita, Tim Waterboer, Brock C. Christensen, Curtis L. Petersen, Jeffrey S. Miller, Karl T. Kelsey
Summary: Cytomegalovirus (CMV) infection alters T cell proportions, but does not increase the risk of HPV16 infection or head and neck cancer. Our findings, based on serology and tumor biomarkers, suggest that CMV is associated with worse patient survival.
Article
Medicine, Research & Experimental
Jacob A. Myers, Dawn Schirm, Laura Bendzick, Rachel Hopps, Carly Selleck, Peter Hinderlie, Martin Felices, Jeffrey S. Miller
Summary: This paper investigates the mechanisms and reversal strategies of NK cell exhaustion, and proposes an in vitro model as a valuable tool for studying exhaustion regulation processes.
Article
Immunology
James D. Dahlvang, Jenna K. Dick, Jules A. Sangala, Philippa R. Kennedy, Emily J. Pomeroy, Kristin M. Snyder, Juliette M. Moushon, Claire E. Thefaine, Jianming Wu, Sara E. Hamilton, Martin Felices, Jeffrey S. Miller, Bruce Walcheck, Beau R. Webber, Branden S. Moriarity, Geoffrey T. Hart
Summary: CMV infection alters NK cell phenotype and function, resulting in the generation of adaptive NK cells with enhanced ADCC and cytokine production. The loss of SYK kinase, rather than the absence of FcRy or PLZF, is likely the main driver behind the increased cytotoxicity and cytokine production in adaptive NK cells.
JOURNAL OF IMMUNOLOGY
(2023)
Article
Oncology
Martin Felices, Erin Wesley, Laura E. Bendzick, Behiye Kodal, Rachel Hopps, Bartosz Grzywacz, Peter Hinderlie, Jeffrey S. Miller, Melissa A. Geller
Summary: We investigated the effects of combined treatment with an IL15 superagonist (N-803) and immune checkpoint blockade (ICB) on immune activation in ovarian cancer patients. Our results showed that N-803 stimulated initial expansion of natural killer (NK) cells in patients, and combining ICB enhanced NK cell function. In preclinical studies, the combination of N-803 and ICB also showed improved anti-tumor control and enhanced NK cell persistence and expansion in vivo.
CANCER IMMUNOLOGY RESEARCH
(2023)
Review
Oncology
Jawad Fares, Zachary B. Davis, Julian S. Rechberger, Stephanie A. Toll, Jonathan D. Schwartz, David J. Daniels, Jeffrey S. Miller, Soumen Khatua
Summary: Despite current treatment advancements for brain tumors, including surgery, chemotherapy, and radiation, the prognosis remains poor, especially for recurrent cases. The close proximity to delicate neural structures often prevents complete surgical removal, and the toxicities of systemic therapy are a concern. However, the field of NK cell-based cancer therapy shows promise as a new avenue for treating brain tumors.
NPJ PRECISION ONCOLOGY
(2023)
Article
Hematology
Shernan G. Holtan, Andrea Hoeschen, Qing Cao, Celalettin Ustun, Brian C. Betts, Najla El Jurdi, Joseph Maakaron, Armin Rashidi, Jeffrey S. Miller, John E. Wagner, Bruce R. Blazar, Pamala A. Jacobson, Angela Panoskaltsis-Mortari, Daniel J. Weisdorf, Margaret L. Macmillan
Summary: Studies have shown that treatments that aid inflammation resolution, immune tolerance, and epithelial repair may improve outcomes for life-threatening acute graft-versus-host disease (aGVHD) beyond traditional immunosuppressants. Addition of urinary-derived human chorionic gonadotropin/epidermal growth factor (uhCG/EGF) to standard aGVHD therapy has been found to be a feasible supportive care measure with potential to reduce morbidity and mortality. Further research is needed to explore the efficacy of uhCG/EGF as a complementary treatment for aGVHD.
TRANSPLANTATION AND CELLULAR THERAPY
(2023)
Article
Hematology
Armin Rashidi, Corinna La Rosa, Julie Curtsinger, Qing Cao, Qiao Zhou, Chetan Raj Lingaraju, Daniel J. Weisdorf, Frank Cichocki, Jeffrey S. Miller, Don J. Diamond
Summary: This study evaluated whether vaccination with a recombinant modified vaccinia Ankara expressing CMV antigens could improve the reconstitution of adaptive NK cells and CMV-specific T cells after auto-HCT in lymphoma and myeloma patients. The results showed that the vaccine increased the abundance of adaptive NK cells and CMV-specific T cells, suggesting a potential role in preventing relapse.
TRANSPLANTATION AND CELLULAR THERAPY
(2022)
Article
Hematology
Nuttavut Sumransub, Qing Cao, Rose Wangen, Claudio Brunstein, Jeffrey S. Miller, Veronika Bachanova
Summary: This study analyzed the patterns of regulatory T cell reconstitution after autologous hematopoietic cell transplantation in non-Hodgkin lymphoma patients and found that the level of proliferating Tregs at day +28 post-transplantation was associated with patient survival.
TRANSPLANTATION AND CELLULAR THERAPY
(2022)
Article
Hematology
Armin Rashidi, Xianghua Luo, Sarah Cooley, Claudio Anasetti, Edmund K. Waller, Claudio G. Brunstein, Frank Cichocki, Daniel J. Weisdorf, Jeffrey S. Miller
Article
Hematology
Martin Felices, Behiye Kodal, Peter Hinderlie, Michael F. Kaminski, Sarah Cooley, Daniel J. Weisdorf, Daniel A. Vallera, Jeffrey S. Miller, Veronika Bachanova