Article
Immunology
Inigo Terren, Victor Sanda, Ainhoa Amarilla-Irusta, Ainara Lopez-Pardo, Arrate Sevilla, Gabirel Astarloa-Pando, Laura Amo, Olatz Zenarruzabeitia, Luca Scorrano, Francisco Borrego
Summary: Cytokine-induced memory-like (CIML) NK cells, stimulated with IL-12, IL-15 and IL-18, show promise in cancer immunotherapy. However, the mitochondrial dynamics of these cells remain unknown. This study found that IL-12/15/18 stimulation led to decreased viability and increased superoxide levels in NK cells, along with changes in mitochondrial morphology possibly mediated by decreased levels of OPA1 protein. While mitophagy was slightly impaired, an increase in autophagic flux was observed. These findings are important for improving the mitochondrial fitness and therapeutic efficacy of IL-12/15/18-stimulated NK cells.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Oncology
Michelle K. Becker-Hapak, Niraj Shrestha, Ethan McClain, Michael J. Dee, Pallavi Chaturvedi, Gilles M. Leclerc, Lynne I. Marsala, Mark Foster, Timothy Schappe, Jennifer Tran, Sweta Desai, Carly C. Neal, Patrick Pence, Pamela Wong, Julia A. Wagner, David A. Russler-Germain, Xiaoyun Zhu, Catherine M. Spanoudis, Victor L. Gallo, Christian A. Echeverri, Laritza L. Ramirez, Lijing You, Jack O. Egan, Peter R. Rhode, Jin-an Jiao, Gabriela J. Muniz, Emily K. Jeng, Caitlin A. Prendes, Ryan P. Sullivan, Melissa M. Berrien-Elliott, Hing C. Wong, Todd A. Fehniger
Summary: NK cells show promise as a cellular therapy for cancer, but challenges in production of required reagents exist. A novel HFPC platform was developed to activate NK cells against cancer, showing potential for advancement in clinical GMP-grade memory-like NK cell production.
CANCER IMMUNOLOGY RESEARCH
(2021)
Article
Oncology
Siyu Zhu, Chen Zhang, Qian Sun, Yang Wang, Wenwen Yu, Feng Wei, Xiubao Ren
Summary: This study establishes a CD3+CD56+ NKT-like cell model and investigates its role and mechanism in antitumor and antiviral immune responses through simulating the effects of cytokines.
JOURNAL OF ONCOLOGY
(2022)
Article
Oncology
Siyu Zhu, Chen Zhang, Qian Sun, Yang Wang, Wenwen Yu, Feng Wei, Xiubao Ren
Summary: Our study demonstrated that cytokines IL-12/15/18 can induce enhanced training immunity in CD3+CD56+ NKT-like cells, leading to a memory-like phenomenon characterized by increased IFN-gamma production, improved cell function, and proliferation potential. Additionally, IL-12/15/18 showed efficacy in promoting antitumor immune responses in NK-cell-sensitive tumor cells.
JOURNAL OF ONCOLOGY
(2022)
Review
Cell & Tissue Engineering
Mubin Tarannum, Rizwan Romee
Summary: NK cells can exhibit memory-like features, altering their lifespan and function through cytokine-induced methods to enhance anticancer effects. Current research indicates that these memory-like NK cells have great potential for clinical applications.
STEM CELL RESEARCH & THERAPY
(2021)
Article
Biochemistry & Molecular Biology
Soo-Hyeon Lee, Yu-Jin Lim, Cheol-Jung Kim, Dohyeon Yu, Je-Jung Lee, Jeong Won Hong, Yeon-Ju Baek, Ji-Youn Jung, Dong-Jun Shin, Sang-Ki Kim
Summary: The study demonstrated that recombinant canine IL-15 (rcIL-15) injections in dogs promoted the selective proliferation and activation of anti-cancer effector cells without serious side effects, indicating the potential value of rcIL-15 in enhancing immunity against cancer in dogs.
Article
Oncology
Nadine Landolina, Francesca Romana Mariotti, Tiziano Ingegnere, Claudia Alicata, Biancamaria Ricci, Andrea Pelosi, Irene Veneziani, Bruno Giuseppe Azzarone, Cecilia Garlanda, Alberto Mantovani, Lorenzo Moretta, Enrico Maggi
Summary: This study aimed to investigate the role of IL-1R8 in human NK cells and optimize its silencing conditions. The results showed that silencing IL-1R8 can enhance the activity and anti-tumor response of NK cells.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Article
Oncology
Adam Nelson, Simon Gebremeskel, Brian D. Lichty, Brent Johnston
Summary: The combination of NKT cell activation therapy, oncolytic virotherapy with VSV-IL-15, and PD-1 blockade has been shown to enhance tumor control in pancreatic cancer, providing a promising treatment strategy.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Article
Biochemistry & Molecular Biology
Naomi C. Bosch, Lena-Marie Martin, Caroline J. Voskens, Carola Berking, Barbara Seliger, Gerold Schuler, Niels Schaft, Jan Doerrie
Summary: NK cells play a crucial role in tumor cell rejection, and activating NK cells along with other immune cells can lead to a more comprehensive cellular response. Dendritic cells are capable of enhancing immune responses by activating NK cells and producing IL-12, while IL-15 serves as an important NK cell activator as well.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Oncology
Alvaro Haroun-Izquierdo, Marianna Vincenti, Herman Netskar, Hanna van Ooijen, Bin Zhang, Laura Bendzick, Minoru Kanaya, Pouria Momayyezi, Shuo Li, Merete Thune Wiiger, Hanna Julie Hoel, Silje Zandstra Krokeide, Veronika Kremer, Geir Tjonnfjord, Stephanie Berggren, Kristina Wikstroem, Pontus Blomberg, Evren Alici, Martin Felices, Bjoern oenfelt, Petter Hoeglund, Bahram Valamehr, Hans-Gustaf Ljunggren, Andreas Bjoerklund, Quirin Hammer, Lise Kveberg, Frank Cichocki, Jeffrey S. Miller, Karl-Johan Malmberg, Ebba Sohlberg
Summary: This study demonstrates the feasibility of off-the-shelf therapy with a non-engineered, yet highly specific, NK cell population for hematological malignancies. The expanded adaptive NK cells retained high cytotoxicity and efficiently killed leukemia cells from AML patients.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Article
Oncology
Celia C. Cubitt, Ethan McClain, Michelle Becker-Hapak, Jennifer A. Foltz, Pamela Wong, Julia A. Wagner, Carly C. Neal, Nancy D. Marin, Lynne Marsala, Mark Foster, Timothy Schappe, Patrick Soon-Shiong, John Lee, Melissa M. Berrien-Elliott, Todd A. Fehniger
Summary: This study describes the creation of a novel triple-cytokine fusion molecule, 18/12/TxM, using the N-803 scaffold fused to IL-18 and IL-12p70. The molecule exhibits trispecific cytokine activity and induces similar activation and memory-like differentiation of NK cells, as well as anti-tumor activity, compared to the individual cytokines.
MOLECULAR THERAPY-ONCOLYTICS
(2022)
Article
Biochemistry & Molecular Biology
Melanie A. MacMullan, Pin Wang, Nicholas A. Graham
Summary: This study used phospho-proteomics to characterize cytokine signaling in NK cells. The results showed that IL-2 and IL-15 induced highly similar signaling in NK cells and identified novel signaling events with potential functional significance. Additionally, the study found that the p90RSK family played a crucial role in IL-2 and IL-15-induced cell proliferation.
Article
Oncology
Yaya Chu, Gaurav Nayyar, Susiyan Jiang, Jeremy M. Rosenblum, Patrick Soon-Shiong, Jeffrey T. Safrit, Dean A. Lee, Mitchell S. Cairo
Summary: The study demonstrates that the combination of N-803 with dinutuximab and exPBNK cells significantly enhances the anti-tumor effects against GD2(+) solid tumors, by enhancing NK cell activity and anti-tumor actions, reducing the secretion of various factors from tumor cells, and extending the survival time of mice.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2021)
Article
Oncology
Tan-Huy Chu, Manh-Cuong Vo, Thangaraj Jaya Lakshmi, Seo-Yeon Ahn, Mihee Kim, Ga-Young Song, Deok-Hwan Yang, Jae-Sook Ahn, Hyeoung-Joon Kim, Sung-Hoon Jung, Je-Jung Lee
Summary: The study suggests that novel multipotent mDCs generated by the addition of IL-15 exhibit outstanding activation of T cells, CIK cells, and NK cells, which may facilitate cellular immunotherapy for cancer patients by inducing strong cytotoxicity against myeloma cells.
TRANSLATIONAL ONCOLOGY
(2022)
Article
Cell Biology
Shinya Abe, Takuma Asahi, Takahiro Hara, Guangwei Cui, Akihiro Shimba, Shizue Tani-ichi, Kohei Yamada, Kazuko Miyazaki, Hitoshi Miyachi, Satsuki Kitano, Naotoshi Nakamura, Junichi Kikuta, Alexis Vandenbon, Masaki Miyazaki, Ryo Yamada, Toshiaki Ohteki, Masaru Ishii, Veronika Sexl, Takashi Nagasawa, Koichi Ikuta
Summary: This study reveals that hematopoietic cells, particularly monocytes and dendritic cells, are the cellular source of IL-15 for NK cell development in the bone marrow. Additionally, it demonstrates that BM NK cells are localized in scattered and clustered compartments, suggesting distinct functions in the immune response.
Article
Hematology
Todd A. Fehniger, Jeffrey S. Miller, Robert K. Stuart, Sarah Cooley, Amandeep Salhotra, Julie Curtsinger, Peter Westervelt, John F. DiPersio, Timothy M. Hillman, Nova Silver, Michael Szarek, Leonid Gorelik, Mark W. Lowdell, Eric Rowinsky
BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
(2018)
Letter
Immunology
Jordan S. Orange, Emily M. Mace, Anthony R. French, Wayne M. Yokoyama, Todd A. Fehniger, Megan A. Cooper
Editorial Material
Immunology
Todd A. Fehniger
JOURNAL OF IMMUNOLOGY
(2019)
Article
Immunology
Melissa M. Berrien-Elliott, Yaping Sun, Carly Neal, Aaron Ireland, Maria C. Trissal, Ryan P. Sullivan, Julia A. Wagner, Jeffrey W. Leong, Pamela Wong, Annelise Y. Mah-Som, Terrence N. Wong, Timothy Schappe, Catherine R. Keppel, Victor S. Cortez, Efstathios G. Stamatiades, Ming O. Li, Marco Colonna, Daniel C. Link, Anthony R. French, Megan A. Cooper, Wei-Le Wang, Mark P. Boldin, Pavan Reddy, Todd A. Fehniger
Article
Cell Biology
Madison R. Mack, Jonathan R. Brestoff, Melissa M. Berrien-Elliott, Anna M. Trier, Ting-Lin B. Yang, Matthew McCullen, Patrick L. Collins, Haixia Niu, Nancy D. Bodet, Julia A. Wagner, Eugene Park, Amy Z. Xu, Fang Wang, Rebecca Chibnall, M. Laurin Council, Carrie Heffington, Friederike Kreisel, David J. Margolis, David Sheinbein, Paola Lovato, Eric Vivier, Marina Cella, Marco Colonna, Wayne M. Yokoyama, Eugene M. Oltz, Todd A. Fehniger, Brian S. Kim
SCIENCE TRANSLATIONAL MEDICINE
(2020)
Article
Cell Biology
Carissa Dege, Katherine H. Fegan, J. Philip Creamer, Melissa M. Berrien-Elliott, Stephanie A. Luff, Darren Kim, Julia A. Wagner, Paul D. Kingsley, Kathleen E. McGrath, Todd A. Fehniger, James Palis, Christopher M. Sturgeon
DEVELOPMENTAL CELL
(2020)
Article
Hematology
Margery Gang, Nancy D. Marin, Pamela Wong, Carly C. Neal, Lynne Marsala, Mark Foster, Timothy Schappe, Wei Meng, Jennifer Tran, Maximilian Schaettler, Marco Davila, Feng Gao, Amanda F. Cashen, Nancy L. Bartlett, Neha Mehta-Shah, Brad S. Kahl, Miriam Y. Kim, Matthew L. Cooper, John F. DiPersio, Melissa M. Berrien-Elliott, Todd A. Fehniger
Article
Cell Biology
Julia A. Wagner, Pamela Wong, Timothy Schappe, Melissa M. Berrien-Elliott, Celia Cubitt, Natalia Jaeger, Madeline Lee, Cassie R. Keppel, Nancy D. Marin, Jennifer A. Foltz, Lynne Marsala, Carly C. Neal, Ryan P. Sullivan, Stephanie E. Schneider, Molly P. Keppel, Nermina Saucier, Megan A. Cooper, Todd A. Fehniger
Article
Biology
Justin T. Gunesch, Amera L. Dixon, Tasneem A. M. Ebrahim, Melissa M. Berrien-Elliott, Swetha Tatineni, Tejas Kumar, Everardo Hegewisch-Solloa, Todd A. Fehniger, Emily M. Mace
Article
Hematology
Aabha Oza, Michael P. Rettig, Phil Powell, Kathryn O'Brien, David B. Clifford, Julie Ritchey, Leah Gehrs, Julia Hollaway, Eugene Major, Todd A. Fehniger, Christopher A. Miller, Patrick Soon-Shiong, Amy Rock, John F. DiPersio
Article
Oncology
Shama Jaswal, Vanessa Sanders, Priyanka Pullarkat, Stephanie Teja, Amber Salter, Marcus P. Watkins, Norman Atagu, Daniel R. Ludwig, Joyce Mhlanga, Vincent M. Mellnick, Linda R. Peterson, Nancy L. Bartlett, Brad S. Kahl, Todd A. Fehniger, Armin Ghobadi, Amanda F. Cashen, Neha Mehta-Shah, Joseph E. Ippolito
Summary: In many cancers, including lymphoma, males have higher incidence and mortality than females. One mechanism underlying this phenomenon is sex differences in metabolism, both with respect to tumor nutrient consumption and systemic alterations in metabolism, i.e., obesity. This study found that visceral fat and tumor glucose uptake can predict outcomes in DLBCL patients in a sex-specific fashion.
Review
Hematology
Melissa M. Berrien-Elliott, Miriam T. Jacobs, Todd A. Fehniger
Summary: Interest in adoptive cell therapy for cancer is growing, and natural killer (NK) cells are being explored as an alternative to T cells. NK cells have advantages such as immediate availability, no graft-versus-host disease, and lower toxicity. Basic advances in NK cell biology and engineering have led to promising clinical trials and the development of off-the-shelf cellular therapies for blood cancers.
Article
Hematology
Margery Gang, Pamela Wong, Melissa M. Berrien-Elliott, Todd A. Fehniger
SEMINARS IN HEMATOLOGY
(2020)