Review
Immunology
Minchuan Zhang, Kong-Peng Lam, Shengli Xu
Summary: NK cell engagers are a promising approach for cancer treatment, activating NK cells and leading to tumor cell lysis. More research is needed to determine how the molecular design of NKCEs affects their functionality and manufacturability.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Oncology
Antonio Tapia-Galisteo, Luis alvarez-Vallina, Laura Sanz
Summary: Immune cell engagers are modified antibodies that have one arm binding a tumor-associated antigen and another arm binding an activating receptor in immune effector cells. These engagers have the potential to revolutionize the treatment of hematological malignancies and are more potent than conventional monoclonal antibodies. The field is growing rapidly, with multiple formats and targets currently in clinical trials, and trispecific antibodies show even more promise by targeting additional tumor-associated antigens or costimulatory receptors.
JOURNAL OF HEMATOLOGY & ONCOLOGY
(2023)
Review
Immunology
Jacob C. Bjorgen, Jenna K. Dick, Ross Cromarty, Geoffrey T. Hart, Joshua Rhein
Summary: NK cells play a crucial role in the early immune response against viral infections. However, changes in their frequency, location, and subtype can lead to dysregulation, which can contribute to host pathology. Therapeutic approaches to address NK cell dysregulation have been explored in cancer research, but are largely understudied in the context of viral infections.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Medicine, Research & Experimental
Henk van Faassen, Dong-Hyeon Jo, Shannon Ryan, Michael J. Lowden, Shalini Raphael, C. Roger MacKenzie, Seung-Hwan Lee, Greg Hussack, Kevin A. Henry
Summary: Novel llama single-domain antibodies against CD16 showed high affinity for human and cynomolgus monkey CD16, but not murine CD16. These antibodies may have applications in cancer immunotherapy.
MOLECULAR PHARMACEUTICS
(2021)
Article
Chemistry, Multidisciplinary
Supriya Prakash, Ninad Kumbhojkar, Andrew Lu, Neha Kapate, Vineeth Chandran Suja, Kyung Soo Park, Lily Li-Wen Wang, Samir Mitragotri
Summary: Natural killer (NK) cell therapies have limitations in efficacy due to low persistence and anergy. This study introduces a material-based approach called microparticles as cell engagers (MACE), which uses polymeric micropatches to sustain and activate NK cells. The activated NK cells bound to MACE exhibit viability, transendothelial migration, and antitumor activity. MACE also activates other immune cells and shows superior antitumor efficacy in a mouse melanoma lung metastasis model. Overall, MACE offers a simple and effective platform to improve NK cell therapy.
Article
Immunology
Philippa R. Kennedy, Daniel A. Vallera, Brianna Ettestad, Caroline Hallstrom, Behiye Kodal, Deborah A. Todhunter, Laura Bendzick, Peter Hinderlie, Joshua T. Walker, Brittany Pulkrabek, Ira Pastan, Robert A. Kratzke, Naomi Fujioka, Jeffrey S. Miller, Martin Felices
Summary: This study examined the state of circulating mononuclear cells in NSCLC patients and found an immunosuppressive environment in advanced NSCLC, which limits treatment efficacy. The researchers designed a TriKE to enhance NK cell cytotoxicity against NSCLC targets, indicating its potential to improve current lung cancer therapies.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Oncology
Daniel A. Vallera, Felix Oh, Behiye Kodal, Peter Hinderlie, Melissa A. Geller, Jeffrey S. Miller, Martin Felices
Summary: HER2 is a crucial marker in breast cancer therapy, but targeting it in ovarian cancer has shown disappointing results, requiring a more comprehensive approach. A new tri-specific biological drug has been designed to enhance NK cell killing of cancer cells and suppress tumor growth by delivering a natural cytokine signal. The study focuses on a nanobody platform technology that combines targeting and cytokine priming to improve efficacy in ovarian cancer treatment.
Review
Immunology
Olivier Demaria, Laurent Gauthier, Guilhaume Debroas, Eric Vivier
Summary: Immuno-oncology is revolutionizing cancer treatment by inducing the immune system to recognize and eliminate tumor cells. Despite successes, alternative strategies are needed to broaden and strengthen anti-tumor immune responses.
EUROPEAN JOURNAL OF IMMUNOLOGY
(2021)
Article
Immunology
Carolyn Shembrey, Momeneh Foroutan, Frederic Hollande
Summary: The protective role of NK cell tumour immunosurveillance in CRC has been recognized, but most patients have limited intra-tumoral NK cell infiltration. To identify patients with high NK cell activity, a novel CRC-specific NK cell gene signature was derived and validated. This signature is highly specific for CRC-infiltrating NK cells and includes genes representative of NK cell maturation, activation status, and anatomical origin.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Guangyu Lian, Thomas Shiu-Kwong Mak, Xueqing Yu, Hui-Yao Lan
Summary: This article reviews the challenges encountered by NK cells in the solid tumor microenvironment and the therapeutic approaches to overcome these limitations. It also outlines the recent preclinical advances and the latest clinical outcomes of NK-based immunotherapies for solid tumors, as well as promising strategies to optimize current NK-targeted immunotherapies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Oncology
Anais Jimenez-Reinoso, Nestor Tirado, Alba Martinez-Moreno, Victor M. Diaz, Marina Garcia-Peydro, Oana Hangiu, Laura Diez-Alonso, Angela Albitre, Petronila Penela, Maria L. Toribio, Pablo Menendez, Luis Alvarez-Vallina, Diego Sanchez Martinez
Summary: CD1a-STAb T cells could be an alternative to CD1a-CAR T cells for coT-ALL patients with aggressive and hyperleukocytic relapses and limited numbers of non-leukemic effector T cells.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Article
Oncology
Karen J. Froning, Arlene Sereno, Flora Huang, Stephen J. Demarest
Summary: T cell receptor (TCR) therapeutics have the unique ability to recognize intracellular antigens on virus-infected or cancerous cells. In this study, recombinant TCR/anti-CD3 bifunctionals directed towards NY-ESO-1 or MAGE-A3 were generated with various molecular formats. The results showed that the potency of inducing redirected lysis activity against tumors was highly restricted to small, tandem binding formats with an rTCR/antiCD3 Fab, while molecules with IgG-like or IgG-Fc structures displayed poor activity.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Article
Biochemistry & Molecular Biology
Xianwu Wang, Xi Luo, Yunpeng Tian, Ting Wu, Jian Weng, Zhu Li, Feng Ye, Xuefei Huang
Summary: The study demonstrates that functionalizing NK cells with cetuximab through metabolic glycoengineering enhances tumor targeting abilities and improves anticancer efficacy against KRAS mutant colon cancer cells.
ACS CHEMICAL BIOLOGY
(2021)
Article
Oncology
Nadine Aschmoneit, Lennart Kuehl, Oliver Seifert, Roland E. Kontermann
Summary: In this study, trivalent, bispecific antibodies were developed for effective killing of HER3-expressing tumor cells with low cytokine release, demonstrating potential advantages in safety profile. The format and orientation of binding sites influenced target cell killing efficacy, T-cell activation, and T-cell-mediated target cell killing, with beneficial effects observed when the CD3 binding site was located in the scDb moiety.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2021)
Review
Oncology
Kirit Singh, Kelly M. Hotchkiss, Aditya A. Mohan, Jessica L. Reedy, John H. Sampson, Mustafa Khasraw
Summary: Glioblastoma is the most common primary brain tumor in adults with a uniformly lethal prognosis. While immunotherapies have not shown significant clinical benefit in treatment, bispecific T-cell engagers are promising antibody fragment therapies. However, the challenges posed by the tumor microenvironment, immune privilege, and blood-brain barrier suggest that a single agent approach may be insufficient for lasting antitumor efficacy.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2021)