Review
Oncology
Sainiteesh Maddineni, John L. Silberstein, John B. Sunwoo
Summary: This article reviews multiple approaches for allogeneic NK cell therapy and discusses the advantages and disadvantages of each method. In recent years, NK cells have become increasingly important players in the immune response against cancer.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Article
Oncology
Yi-Chiu Kuo, Cheng-Fu Kuo, Kurt Jenkins, Alfur Fu-Hsin Hung, Wen-Chung Chang, Miso Park, Brenda Aguilar, Renate Starr, Jonathan Hibbard, Christine Brown, John C. Williams
Summary: The use of universal CAR T cells shows promise in improving the efficacy of cancer treatment and has broad potential applications.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Review
Oncology
Shi Yong Neo, Shengli Xu, Joni Chong, Kong-Peng Lam, Jing Wu
Summary: Cell therapy is a growing field that involves the use of various types of immune cells, including T cells, for the treatment of human ailments such as cancer. This review focuses on cell therapy in the immuno-oncology space, discussing recent advances in different cell therapies and strategies to enhance therapeutic responses. Additionally, potential alternative immune cell types are explored to overcome the limitations of conventional adoptive cell therapies.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2023)
Article
Oncology
Jiacheng Bi, Chen Huang, Xiaomeng Jin, Chaoyue Zheng, Yingying Huang, Xiaohu Zheng, Zhigang Tian, Haoyu Sun
Summary: By analyzing single-cell transcriptomics and using gene reporter mice, this study found that TIPE2 expression correlated with NK cell exhaustion in the tumor microenvironment (TME) in both humans and mice. Deletion of TIPE2 improved the antitumor activity of adoptively transferred mouse NK cells and human NK cells, either derived from peripheral blood or induced pluripotent stem cells (iPSCs). Additionally, TIPE2 deletion synergized with CISH deletion to further enhance antitumor activity in vivo.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2023)
Article
Oncology
Ilias Christodoulou, Won Jin Ho, Andrew Marple, Jonas W. Ravich, Ada Tam, Ruyan Rahnama, Adam Fearnow, Cambrynne Rietberg, Sean Yanik, Elena E. Solomou, Ravi Varadhan, Michael A. Koldobskiy, Challice L. Bonifant
Summary: The study demonstrates that engineering NK cells to express CARs and IL-15 can enhance their anti-AML activity. However, this modification also comes with potential systemic toxicities.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2021)
Review
Immunology
Cai Zhang, Yuan Hu, Weihua Xiao, Zhigang Tian
Summary: IKCs, particularly NK cells, NKT cells, and gamma delta T cells, exhibit specific tumor recognition and potent antitumor functions, with low risk of developing GVHD, making them potentially excellent candidates for cancer immunotherapy. Advances in synthetic biology and genetic engineering techniques will further optimize IKC-based anticancer therapies.
CELLULAR & MOLECULAR IMMUNOLOGY
(2021)
Article
Oncology
Laura T. Morton, Tassilo L. A. Wachsmann, Miranda H. Meeuwsen, Anne K. Wouters, Dennis F. G. Remst, Marleen M. van Loenen, J. H. Frederik Falkenburg, Mirjam H. M. Heemskerk
Summary: This study combines the antitumor effector functions of NK cells with TCR engineering to create a novel therapeutic strategy that avoids TCR-associated immune resistance and enhances the efficacy of NK cells against tumors.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Article
Oncology
Konstantinos Lontos, Yiyang Wang, Supriya K. Joshi, Andrew T. Frisch, McLane J. Watson, Alok Kumar, Ashley Menk, Yupeng Wang, Rachel Cumberland, Jason Lohmueller, Esteban Carrizosa, Benjamin Boyerinas, Greg M. Delgoffe
Summary: This study demonstrates that an engineered version of the inhibitory transcription factor PGC-1 alpha can metabolically reprogram human CAR-T cells, resulting in improved in vivo efficacy for the treatment of solid tumors. In contrast, a truncated version of PGC-1 alpha, NT-PGC-1 alpha, did not improve the in vivo outcomes.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2023)
Article
Oncology
Congcong Zhang, Jasmin Roeder, Anne Scherer, Malena Bodden, Jordi Pfeifer Serrahima, Anita Bhatti, Anja Waldmann, Nina Mueller, Pranav Oberoi, Winfried S. Wels
Summary: The study developed a bispecific antibody NKAB-ErbB2 that redirects NKG2D-expressing effector cells to ErbB2-positive tumor cells, synergizing with NKG2D-CAR cells and natural NK cell-mediated cytotoxicity. In mouse model, NKAR-NK-92 cells combined with NKAB-ErbB2 effectively suppressed tumor outgrowth and induced antitumor immunity and cures in most animals.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2021)
Article
Immunology
Rui Zheng, Yuankun Chen, Yiting Zhang, Sixin Liang, Xiaojuan Zhao, Yiyi Wang, Pengju Wang, Ruotong Meng, Angang Yang, Bo Yan
Summary: Our study explores the effect of low-affinity CARs using humanized scFvs on the function of CAR-T cells. We find that moderately reducing the affinity of CARs can maintain anti-tumor efficacy and improve the safety of CAR therapy both in vitro and in vivo. In addition, T cells expressing the VL domain only antibody show long-lasting tumor elimination capability and lower cytokine levels.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Oncology
Oezcan Cinar, Bernadette Brzezicha, Corinna Grunert, Peter Michael Kloetzel, Christin Beier, Caroline Anna Peuker, Ulrich Keller, Antonio Pezzutto, Antonia Busse
Summary: Adoptive transfer of T cells engineered to target specific mutations in B-cell lymphoma has shown promising results in preclinical studies, suggesting a potential novel treatment strategy with high tumor specificity. The engineered T cells exhibited mutation-specific reactivity and therapeutic efficacy in killing lymphoma cell lines carrying the targeted mutation. Initial safety screening also indicated a lack of off-target reactivity, supporting the feasibility and safety of using mutation-specific TCRs for precision therapy in a subgroup of B-cell malignancies.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2021)
Article
Oncology
Xuan Guo, Tanel Mahlakoiv, Qian Ye, Srinivas Somanchi, Shuyang He, Hemlata Rana, Andrea DiFiglia, Joseph Gleason, William van der Touw, Robert Hariri, Xiaokui Zhang
Summary: The study successfully achieved 94% knockout efficiency of CBLB using CRISPR/Cas9 technology in placental CD34(+) cells, demonstrating the negative regulatory role of CBLB in PNK cell cytotoxicity against tumor cells. Ablation of CBLB did not impact PNK cell proliferation, differentiation, or phenotypical characteristics, but resulted in enhanced cytotoxicity against tumor cells. Furthermore, CBLB knockout PNK cells showed increased in vivo proliferation, maturation, and antitumor activity compared to unmodified PNK cells.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2021)
Review
Oncology
Sophia Stock, Anna-Kristina Kluever, Luisa Fertig, Vivien D. Menkhoff, Marion Subklewe, Stefan Endres, Sebastian Kobold
Summary: The clinical application of CAR T-cell therapy has revolutionized the treatment options for certain terminally ill patients with blood-borne cancers. However, the therapy can lead to severe toxicities, and efforts are being made to better control CAR T-cell activity and manage its associated side effects through various strategies and mechanisms.
INTERNATIONAL JOURNAL OF CANCER
(2023)
Article
Oncology
Loic Reppel, Ourania Tsahouridis, Jason Akulian, Ian J. Davis, Hong Lee, Giovanni Fuca, Jared Weiss, Gianpietro Dotti, Chad Pecot, Barbara Savoldo
Summary: This study suggests that GD2 is a promising target for CAR-T cell therapy in lung cancer, and the use of tazemetostat can upregulate GD2 expression in tumor cells, enhancing their susceptibility to CAR-T cell targeting.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Review
Oncology
Kai Dai, Yin Wu, Sha She, Qian Zhang
Summary: CAR-NK cells, as a revolutionary cellular immunotherapy, have the potential to kill hepatocellular carcinoma cells independently of major histocompatibility complex matching, and recent advances in genetic engineering have been made, but challenges still exist.
WORLD JOURNAL OF GASTROINTESTINAL ONCOLOGY
(2021)
Article
Chemistry, Multidisciplinary
Guillaume Le Saux, Netanel Bar-Hanin, Avishay Edri, Uzi Hadad, Angel Porgador, Mark Schvartzman
ADVANCED MATERIALS
(2019)
Article
Immunology
Orit Berhani, Ariella Glasner, Shira Kahlon, Alexandra Duev-Cohen, Rachel Yamin, Elad Horwitz, Jonatan Enk, Ofra Moshel, Alexandar Varvak, Angel Porgador, Stipan Jonjic, Ofer Mandelboim
EUROPEAN JOURNAL OF IMMUNOLOGY
(2019)
Review
Pathology
Tomasz Powrozek, Angel Porgador, Teresa Malecka-Massalska
EXPERT REVIEW OF MOLECULAR DIAGNOSTICS
(2020)
Article
Biochemistry & Molecular Biology
Anil Khushalrao Shendge, Rhitajit Sarkar, Nripendranath Mandal
JOURNAL OF FOOD BIOCHEMISTRY
(2020)
Article
Cell Biology
Lee Shaashua, Shimrit Mayer, Chen Lior, Hagar Lavon, Alexander Novoselsky, Ruth Scherz-Shouval
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2020)
Article
Multidisciplinary Sciences
Oshrat Levi-Galibov, Hagar Lavon, Rina Wassermann-Dozorets, Meirav Pevsner-Fischer, Shimrit Mayer, Esther Wershof, Yaniv Stein, Lauren E. Brown, Wenhan Zhang, Gil Friedman, Reinat Nevo, Ofra Golani, Lior H. Katz, Rona Yaeger, Ido Laish, John A. Porco, Erik Sahai, Dror S. Shouval, David Kelsen, Ruth Scherz-Shouval
NATURE COMMUNICATIONS
(2020)
Article
Oncology
Nil Grunberg, Meirav Pevsner-Fischer, Tal Goshen-Lago, Judith Diment, Yaniv Stein, Hagar Lavon, Shimrit Mayer, Oshrat Levi-Galibov, Gil Friedman, Yifat Ofir-Birin, Li-Jyun Syu, Cristina Migliore, Eyal Shimoni, Salomon M. Stemmer, Baruch Brenner, Andrzej A. Dlugosz, David Lyden, Neta Regev-Rudzki, Irit Ben-Aharon, Ruth Scherz-Shouval
Summary: This study used RNA sequencing of CAFs from gastric cancer patients to identify a stromal gene signature associated with aggressive gastric cancer, with HSF1 playing a key regulatory role in this signature. HSF1 upregulates inhibin subunit beta A and thrombospondin 2, which are secreted in CAF-derived extracellular vesicles to promote cancer progression.
Article
Multidisciplinary Sciences
Aner Ottolenghi, Priyanka Bolel, Rhitajit Sarkar, Yariv Greenshpan, Muhammed Iraqi, Susmita Ghosh, Baisali Bhattacharya, Zoe Taylor, Kiran Kundu, Olga Radinsky, Roi Gazit, David Stepensky, Ron N. Apte, Elena Voronov, Angel Porgador
Summary: The study extended the half-life of IL-2 by flanking its core with sequences from the NCR2 receptor, creating a modified IL-2 called S2A.
S2A significantly enhanced induction of Tregs in vivo but did not reduce the metastatic capacity of melanoma in a mouse model, showing promising therapeutic effects in autoimmune models.
SCIENTIFIC REPORTS
(2021)
Article
Oncology
Roni Shouval, Ana Alarcon Tomas, Joshua A. Fein, Jessica R. Flynn, Ettai Markovits, Shimrit Mayer, Aishat Olaide Afuye, Anna Alperovich, Theodora Anagnostou, Michal J. Besser, Connie Lee Batlevi, Parastoo B. Dahi, Sean M. Devlin, Warren B. Fingrut, Sergio A. Giralt, Richard J. Lin, Gal Markel, Gilles Salles, Craig S. Sauter, Michael Scordo, Gunjan L. Shah, Nishi Shah, Ruth Scherz-Shouval, Marcel van den Brink, Miguel-Angel Perales, Maria Lia Palomba
Summary: TP53 mutations/CNAs are important determinants of response and survival in LBCL patients treated with CD19-CAR-T therapy. TP53 alterations are associated with poor treatment outcomes and lower survival rates.
JOURNAL OF CLINICAL ONCOLOGY
(2022)
Article
Oncology
Coral Halperin, Joschka Hey, Dieter Weichenhan, Yaniv Stein, Shimrit Mayer, Pavlo Lutsik, Christoph Plass, Ruth Scherz-Shouval
Summary: The first genome-wide map of DNA methylation in breast cancer-associated fibroblasts reveals a previously unknown facet of the dynamic plasticity of the stroma.
Article
Multidisciplinary Sciences
Lee Shaashua, Aviad Ben-Shmuel, Meirav Pevsner-Fischer, Gil Friedman, Oshrat Levi-Galibov, Subhiksha Nandakumar, Debra Barki, Reinat Nevo, Lauren E. Brown, Wenhan Zhang, Yaniv Stein, Chen Lior, Han Sang Kim, Linda Bojmar, William R. Jarnagin, Nicolas Lecomte, Shimrit Mayer, Roni Stok, Hend Bishara, Rawand Hamodi, Ephrat Levy-Lahad, Talia Golan, John A. Porco, Christine A. Iacobuzio-Donahue, Nikolaus Schultz, David A. Tuveson, David Lyden, David Kelsen, Ruth Scherz-Shouval
Summary: Tumors are initiated by mutations in cancer cells and progress through interactions with non-malignant cells of the tumor microenvironment. This study examines how different mutations in cancer cells affect the transcriptional rewiring of cancer-associated fibroblasts (CAFs) in pancreatic cancer. The researchers find that BRCA mutations lead to an increase in a specific subset of immune-regulatory CAFs, mediated by activation of heat-shock factor 1.
NATURE COMMUNICATIONS
(2022)
Article
Oncology
Joschka Hey, Coral Halperin, Mark Hartmann, Shimrit Mayer, Maximilian Schoenung, Daniel B. Lipka, Ruth Scherz-Shouval, Christoph Plass
Summary: This study found that the accumulation of myeloid cells, particularly tumor-associated macrophages, characterizes the tumor microenvironment of many solid cancers, including breast cancer. The presence of cancer cells significantly alters the DNA methylation landscape of macrophages and monocytes. These results suggest that the presence of breast cancer perturbs the epigenetic landscapes of macrophages and monocytes.
INTERNATIONAL JOURNAL OF CANCER
(2023)
Article
Biochemistry & Molecular Biology
Muhammed Iraqi, Priyanka Bolel, Rhitajit Sarkar, Baisali Bhattacharya, Muhammad Abu Ahmad, Avishay Edri, Laila C. Roisman, Moshe Elkabets, Walid Shalata, Nir Peled, Angel Porgador
Summary: Lung cancer cells in the tumor microenvironment have immune evasion properties that lead to the failure of conventional chemotherapies. This study found that personalized chemotherapy, combined with the peptide R11-NLS-pep8, can enhance the antineoplastic effect of chemotherapies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Oncology
Gil Friedman, Oshrat Levi-Galibov, Eyal David, Chamutal Bornstein, Amir Giladi, Maya Dadiani, Avi Mayo, Coral Halperin, Meirav Pevsner-Fischer, Hagar Lavon, Shimrit Mayer, Reinat Nevo, Yaniv Stein, Nora Balint-Lahat, Iris Barshack, H. Raza Ali, Carlos Caldas, Einav Nili-Gal-Yam, Uri Alon, Ido Amit, Ruth Scherz-Shouval
Article
Multidisciplinary Sciences
Ran Yahalom, David Barishev, Alon Steren, Yonatan Nameri, Maxim Roytman, Angel Porgador, Yuval Elovici