Review
Medicine, Research & Experimental
Kerry A. Whalen, Kavya Rakhra, Naveen K. Mehta, Alexander Steinle, Jennifer S. Michaelson, Patrick A. Baeuerle
Summary: The field of immuno-oncology has revolutionized cancer patient care, but there are still challenges with current therapeutic approaches targeting T cells. Engaging the innate immune system, especially natural killer (NK) cells, has emerged as a promising modality in immunotherapy. This review focuses on therapeutic strategies that selectively engage NK cells for cancer therapy, particularly targeting the activating receptors NKG2D and CD16A.
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
Oncology
Fei Gao, Mauricio Campos Mora, Michael Constantinides, Lois Coenon, Caroline Multrier, Loic Vaillant, Tianxiang Zhang, Martin Villalba
Summary: This study found significant phenotypical and functional differences between g-NK cells in umbilical cord blood and peripheral blood. Unlike g-NK cells in peripheral blood, g-NK cells in umbilical cord blood do not show heightened cytokine production upon CD16 engagement. However, they exhibit elevated levels of IFN-gamma production after in vitro activation, particularly when co-cultured with human cytomegalovirus and plasma from g-NK positive adults.
Article
Immunology
Antonio Hrvat, Mathias Schmidt, Martin Obholzer, Sonja Benders, Sebastian Kollenda, Peter A. Horn, Matthias Epple, Sven Brandau, Nina Mallmann-Gottschalk
Summary: The study explores the effects of different CaP-NPs on the anti-tumor activity of natural killer (NK) cells. Aggregated CaP-NPs can activate NK cell degranulation and impair antibody-dependent cellular cytotoxicity (ADCC). However, when properly dissolved, they do not cause substantial activation. Functionalized CaP-NPs coupled with therapeutic antibodies maintain high levels of ADCC activity.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Geriatrics & Gerontology
Rongjiao Liu, Qizhi Luo, Weiguang Luo, Ling Wan, Quan Zhu, Xiangli Yin, Xiaofang Lu, Zixuan Song, Leiyan Wei, Zhiqing Xiang, Yizhou Zou
Summary: In this study, a soluble NKCAR was designed to trigger NK cell cytotoxicity by binding with the ligand MICA through the NKG2D receptor expressed on NK cells. The NKCAR showed bifunctional activity, recognizing both the CD20 antigen of target cells and the NKG2D receptor of NKL cells. The soluble NKCAR mediated the killing of CD20(+) Daudi cells in vitro, indicating its potential clinical application for killing target tumor cells.
Article
Biochemistry & Molecular Biology
Haeryung Cho, Woo-Chang Son, Young-Shin Lee, Eun Jung Youn, Chi-Dug Kang, You-Soo Park, Jaeho Bae
Summary: Histone acetylation is an epigenetic mechanism that regulates gene expression, including NKG2D ligands. Specific types of HDAC genes, particularly HDAC1 and HDAC2, may be key regulators of NKG2D ligand expression. Inhibiting HDAC1 and HDAC2 could induce NKG2D ligand expression, potentially enhancing NK cell-mediated anti-cancer immunity.
Article
Biochemistry & Molecular Biology
Christian Kellner, Sebastian Lutz, Hans-Heinrich Oberg, Daniela Wesch, Anna Otte, Katarina J. Diemer, Hauke Wilcken, Dirk Bauerschlag, Claus-Christian Glueer, Christian Wichmann, Dieter Kabelitz, Jeanette H. W. Leusen, Katja Klausz, Andreas Humpe, Martin Gramatzki, Matthias Peipp
Summary: Combining NKG2D ligand ULBP2 with HER2-targeting scFv can effectively trigger NK cell killing of HER2-positive breast cancer cells. This immunoligand not only induces tumor cell lysis, but also enhances antibody-dependent cell-mediated cytotoxicity against tumor cells.
BIOLOGICAL CHEMISTRY
(2022)
Article
Immunology
Minjing Zou, Suhad Al-Yahya, Monther Al-Alwan, Huda A. BinEssa, Khalid S. A. Khabar, Falah Almohanna, Abdullah M. Assiri, Abdulmohsen Altaweel, Amal Qattan, Brian F. Meyer, Ali S. Alzahrani, Yufei Shi
Summary: BRAF(V600E) mutations are common in papillary thyroid cancer (PTC), and beta-catenin is often overexpressed in PTC. Tumors driven by BRAF(V600E) rely on Wnt/beta-catenin signaling for growth and progression.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Oncology
Zhaoming Wang, Michael S. Chimenti, Christopher Strouse, George J. Weiner
Summary: The study found that T cell help, mainly mediated by local production of IL2, plays a significant role in enhancing NK cell-mediated antibody-dependent cellular cytotoxicity and viability. Activating T cells can improve the efficacy of anti-CD20 and other mAb therapies, particularly when NK-mediated antibody-dependent cellular cytotoxicity is the primary mechanism of action.
CANCER IMMUNOLOGY IMMUNOTHERAPY
(2022)
Review
Immunology
Feifei Li, Sheng Liu
Summary: This review provides an overview of the role of natural killer (NK) cells and antibody-dependent cellular cytotoxicity (ADCC) in targeted therapy of HER2-positive breast cancer, as well as recent strategies to leverage our knowledge of NK cells and ADCC as an immunotherapy approach.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Cell Biology
Jagoda Siemaszko, Aleksandra Marzec-Przyszlak, Katarzyna Bogunia-Kubik
Summary: Natural Killer (NK) cells are natural cytotoxic cells of the innate immune system that can recognize and attack transformed or infected cells through their NKG2D receptor, which has significant immunological functions and clinical relevance.
Review
Immunology
Fei Gao, Zhengwei Zhou, Ying Lin, Guang Shu, Gang Yin, Tianxiang Zhang
Summary: Adaptive NK cells play a significant role in the innate immune system by exhibiting specialized antibody-dependent response and adaptive immune features. They have been found to have important implications in viral infections, leukemia treatment, and adoptive cell therapy for cancer.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Oncology
Zhaoming Wang, Chaobo Yin, Lawrence G. Lum, Andrean Simons, George J. Weiner
Summary: Research suggests that treatment with anti-CD3 x anti-cancer bispecific antibodies (bsAbs) may enhance T cell help, maintaining long-term NK cell-mediated antibody-dependent cellular cytotoxicity (ADCC).
JOURNAL OF HEMATOLOGY & ONCOLOGY
(2021)
Review
Oncology
Kate J. Dixon, Jianming Wu, Bruce Walcheck
Summary: Human natural killer (NK) cells target tumor antigens through interaction with IgG Fc receptors, leading to antibody-dependent cell-mediated cytotoxicity (ADCC) against cancer cells. Engineering monoclonal antibodies and Fc receptors can enhance NK cell-mediated ADCC for cancer treatment. Targeting tumor antigens by modifying the Fc portion of antibodies or the FcR on NK cells is a key focus of research in improving mAb therapy efficacy.
Article
Biotechnology & Applied Microbiology
Emily Chiu, Martin Felices, Frank Cichocki, Zachary Davis, Hongbo Wang, Katie Tuninga, Daniel A. Vallera, Tom Lee, Ryan Bjordahl, Karl Johan Malmberg, Bahram Valamehr, Jeffrey S. Miller
Summary: The researchers developed an immune therapy called NKG2C-KE, which directs specific types of NK cells to attack leukemia cells. This method showed promising results in experiments and could potentially become a new treatment strategy for leukemia.
Editorial Material
Gastroenterology & Hepatology
H. S. S. Bong, Y. S. A. Soh, A. Shabbir, JB-Y So
JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY
(2022)
Article
Surgery
Jun Liang Teh, Hui Yu Tham, Alex Yu Sen Soh, Corrisa Chee, Guowei Kim, Asim Shabbir, Reuben Kong Min Wong, Jimmy Bok Yan So
Summary: This study focused on reflux after POEM, finding that 43.1% of patients had symptomatic reflux, 60% had endoscopic evidence of esophagitis, and 56% had increased acid exposure on pH-impedance test.
SURGICAL ENDOSCOPY AND OTHER INTERVENTIONAL TECHNIQUES
(2022)
Review
Oncology
Yong Xiang Gwee, Daryl Kai Ann Chia, Jimmy So, Wim Ceelen, Wei Peng Yong, Patrick Tan, Chin-Ann Johnny Ong, Raghav Sundar
Summary: Peritoneal metastasis is a common occurrence in advanced gastric cancer and is associated with a poor prognosis. Traditional systemic therapy is often ineffective in treating this specific disease state. Recent studies and clinical trials have focused on understanding the biology of peritoneal metastasis and identifying potential molecular targets. Peritoneal-specific clinical trials are being designed to combine local and systemic therapy for a more effective treatment approach.
JOURNAL OF CLINICAL ONCOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Upadhyayula S. Srinivas, Norbert S. C. Tay, Patrick Jaynes, Akshaya Anbuselvan, Gokula K. Ramachandran, Joanna D. Wardyn, Michal M. Hoppe, Phuong Mai Hoang, Yanfen Peng, Sherlly Lim, May Yin Lee, Praveen C. Peethala, Omer An, Akshay Shendre, Bryce W. Q. Tan, Sherlyn Jemimah, Manikandan Lakshmanan, Longyu Hu, Rekha Jakhar, Karishma Sachaphibulkij, Lina H. K. Lim, Shazib Pervaiz, Karen Crasta, Henry Yang, Patrick Tan, Chao Liang, Lena Ho, Vartika Khanchandani, Dennis Kappei, Wei Peng Yong, David S. P. Tan, Matteo Bordi, Silvia Campello, Wai Leong Tam, Christian Frezza, Anand D. Jeyasekharan
Summary: Inhibitors of PLK1, a mitotic kinase, have objective responses in refractory cancers. However, PLK1 overexpression in cancer does not correlate with drug sensitivity. Through a chemical screen, we found that cells deficient in ARID1A tumor suppressor are highly sensitive to PLK1 inhibition, which is unrelated to canonical PLK1 functions. A CRISPR screen revealed that sensitivity in ARID1A deficient cells is dependent on the mitochondrial translation machinery. These findings highlight a new role for PLK1 in maintaining mitochondrial fitness under metabolic stress and offer a strategy for the therapeutic use of PLK1 inhibitors.
Correction
Biochemistry & Molecular Biology
Upadhyayula S. Srinivas, Norbert S. C. Tay, Patrick Jaynes, Akshaya Anbuselvan, Gokula K. Ramachandran, Joanna D. Wardyn, Michal M. Hoppe, Phuong Mai Hoang, Yanfen Peng, Sherlly Lim, May Yin Lee, Praveen C. Peethala, Omer An, Akshay Shendre, Bryce W. Q. Tan, Sherlyn Jemimah, Manikandan Lakshmanan, Longyu Hu, Rekha Jakhar, Karishma Sachaphibulkij, Lina H. K. Lim, Shazib Pervaiz, Karen Crasta, Henry Yang, Patrick Tan, Chao Liang, Lena Ho, Vartika Khanchandani, Dennis Kappei, Wei Peng Yong, David S. P. Tan, Matteo Bordi, Silvia Campello, Wai Leong Tam, Christian Frezza, Anand D. Jeyasekharan
Editorial Material
Oncology
Daryl K. A. Chia, Jia Jun Ang, Raghav Sundar, Guowei Kim, Asim Shabbir, Jimmy B. Y. So, Wei Peng Yong
ANNALS OF SURGICAL ONCOLOGY
(2022)
Letter
Oncology
Daryl K. A. Chia, Raghav Sundar, Guowei Kim, Jia Jun Ang, Asim Shabbir, Jimmy B. Y. So, Wei Peng Yong
ANNALS OF SURGICAL ONCOLOGY
(2023)
Article
Oncology
Takayuki Yoshino, Thierry Andre, Tae Won Kim, Wei Peng Yong, Kai-Keen Shiu, Benny Vittrup Jensen, Lars Henrik Jensen, Cornelis J. A. Punt, Denis Smith, Rocio Garcia-Carbonero, Julia Alcaide-Garcia, Peter Gibbs, Christelle de la Fouchardiere, Fernando Rivera, Elena Elez, Dung T. Le, Noriaki Adachi, David Fogelman, Patricia Marinello, Luis A. Jr Jr Diaz
Summary: The phase 3 KEYNOTE-177 study compared pembrolizumab with chemotherapy in newly diagnosed MSI-H/dMMR mCRC patients. The study showed that pembrolizumab as a first-line treatment was effective for patients from Asia with MSI-H/dMMR mCRC.
Article
Medicine, Research & Experimental
Win Lwin Thuya, Li Ren Kong, Nicholas L. Syn, Ling -Wen Ding, Esther Sok Hwee Cheow, Regina Tong Xin Wong, Tingting Wang, Robby Miguel Wen-Jing Goh, Hongyan Song, Migara K. Jayasinghe, Minh T. N. Le, Jian Cheng Hu, Wei-Peng Yong, Soo-Chin Lee, Andrea Li-Ann Wong, Gautam Sethi, Huynh The Hung, Paul Chi-Lui Ho, Jean-Paul Thiery, Siu Kwan Sze, Tiannan Guo, Ross A. Soo, Henry Yang, Yaw Chyn Lim, Lingzhi Wang, Boon-Cher Goh
Summary: This study reveals that the cargo protein FAM3C carried by tumor-released extracellular vesicles (EVs) can enhance the growth and metastatic potential of lung cancer cells. FAM3C interacts with RalA protein to activate the Src/Stat3 signaling pathway, promoting oncogenicity. This finding provides a new target for lung cancer therapy.
Article
Oncology
Jerold Loh, Jiaxuan Wu, Jenny Chieng, Aurora Chan, Wei-Peng Yong, Raghav Sundar, Soo-Chin Lee, Andrea Wong, Joline S. J. Lim, David S. P. Tan, Ross Soo, Boon-Cher Goh, Bee-Choo Tai, Cheng E. Chee
Summary: Patient selection is crucial in Phase I studies, particularly in heavily pre-treated patients where prognosis estimation is challenging. Existing prognostic models like the Royal Marsden Hospital (RMH) score or the neutrophil-lymphocyte ratio (NLR) have not been validated in current novel therapies or in the Asian Phase I population.
BRITISH JOURNAL OF CANCER
(2023)
Article
Oncology
Joan Choo, Ley Fang Kua, Mu Yar Soe, Bernadette Reyna Asuncion, Benjamin Kye Jyn Tan, Chong Boon Teo, Ryan Yong Kiat Tay, Jimmy So, Asim Shabbir, Kim Guowei, Hon Lyn Tan, Gloria Chan, Haoran Ma, Gokula Krishnan Ramachandran, Jeffrey H. Y. Lum, Cheng Ean Chee, Sriram Sridharan, Patrick Tan, Raghav Sundar, Wei Peng Yong
Summary: PD-1(+)CD8(+) T-cells in gastric cancer are associated with prognosis, chemotherapy and immunotherapy sensitivity, and tumor microenvironment. Tumors with high PD-1 and CD8A expression levels show improved overall survival with immunotherapy and chemotherapy. CD8PD-1(high) tumors have an immunologically active, T-cell inflamed tumor microenvironment.
Article
Gastroenterology & Hepatology
Chang Xu, Kie Kyon Huang, Jia Hao Law, Joy Shijia Chua, Taotao Sheng, Natasha M. Flores, Melissa Pool Pizzi, Atsushi Okabe, Angie Lay Keng Tan, Feng Zhu, Vikrant Kumar, Xiaoyin Lu, Ana Morales Benitez, Benedict Shi Xiang Lian, Haoran Ma, Shamaine Wei Ting Ho, Kalpana Ramnarayanan, Chukwuemeka George Anene-Nzelu, Milad Razavi-Mohseni, Siti Aishah Binte Abdul Ghani, Su Ting Tay, Xuewen Ong, Ming Hui Lee, Yu Amanda Guo, Hassan Ashktorab, Duane Smoot, Shang Li, Anders Jacobsen Skanderup, Michael A. Beer, Roger Sik Yin Foo, Joel Shi Hao Wong, Kaushal Sanghvi, Wei Peng Yong, Raghav Sundar, Atsushi Kaneda, Shyam Prabhakar, Pawel Karol Mazur, Jaffer A. Ajani, Khay Guan Yeoh, Jimmy Bok-Yan So, Patrick Tan
Summary: This study identified ARID1A as the second most frequently mutated driver gene in gastric cancer (GC). Through genomic and single-cell transcriptomic analysis, the effects of ARID1A mutation on genomic, single-cell, and epigenomic levels were revealed, and a potential therapeutic strategy for ARID1A-mutated GC was discovered.
Review
Gastroenterology & Hepatology
Valencia Ru-Yan Zhang, Gokula Krishnan Ramachandran, Evelyn Xiu Ling Loo, Alex Yu Sen Soh, Wei Peng Yong, Kewin Tien Ho Siah
Summary: This systematic review aimed to identify volatile organic compounds (VOCs) in the diagnosis of irritable bowel syndrome (IBS) through Medline and Cochrane's databases. 57% of the studies showed that VOCs could differentiate IBS patients from healthy controls with AUC ranging from 0.83 to 0.99. Studies distinguishing IBS from inflammatory bowel disease (IBD) patients had slightly higher AUC of 0.87-0.98. Combining VOC into panels allowed the creation of discriminative algorithms. Despite limitations in VOC sampling heterogeneity and small sample sizes, our review suggests that VOC analysis has the potential to be a noninvasive point-of-care test that differentiates IBS from other organic gastrointestinal diseases.
NEUROGASTROENTEROLOGY AND MOTILITY
(2023)
Article
Oncology
Cheng E. Chee, Melissa Ooi, Soo-Chin Lee, Raghav Sundar, Valerie Heong, Wei-Peng Yong, Chin Hin Ng, Andrea Wong, Joline S. J. Lim, David S. P. Tan, Ross Soo, Joshua T. C. Tan, Song Yang, Min Thura, Abdul Qader Al-Aidaroos, Wee Joo Chng, Qi Zeng, Boon-Cher Goh
Summary: This study aims to evaluate the safety and efficacy of PRL3-zumab in patients with advanced solid tumors and hematological malignancies. The results show that PRL3-zumab is safe and tolerable, with stable disease observed in some solid tumor patients.
Letter
Oncology
Daryl K. A. Chia, Raghav Sundar, Guowei Kim, Jia Jun Ang, Asim Shabbir, Jimmy B. Y. So, Wei Peng Yong
ANNALS OF SURGICAL ONCOLOGY
(2023)