Review
Pharmacology & Pharmacy
Ava Safaroghli-Azar, Fatemeh Emadi, Jimma Lenjisa, Laychiluh Mekonnen, Shudong Wang
Summary: As the fifth pillar of cancer treatment, immunotherapy has revolutionized therapeutic strategies by focusing on the host's immune system. The discovery of immune-modulatory effects for kinase inhibitors has opened up new possibilities in this approach, as these small molecule inhibitors not only directly target essential proteins for tumor survival and proliferation, but also stimulate immune responses against malignant cells.
DRUG DISCOVERY TODAY
(2023)
Review
Immunology
Sarah Rumler
Summary: This article discusses the immune therapies for pediatric CNS tumors, including checkpoint inhibitors, vaccines, radiation therapy, and early studies of antibody-mediated immunogenic therapies. The article also highlights the importance of combination immunotherapy and addresses the neurologic toxicities associated with immunotherapies.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Chemistry, Medicinal
Shuai Wang, Fen-Er Chen
Summary: Inhibition of the MDM2-p53 protein-protein interaction using small-molecule inhibitors is a promising strategy for cancer therapy. Many highly potent and selective small-molecule MDM2 inhibitors have been discovered and are currently undergoing different clinical trials. This review provides an overview of the function of MDM2 and the identification, optimization, preclinical, and clinical studies of clinical-stage MDM2 inhibitors. It also discusses challenges, potential toxicity, and future perspectives, which will guide the design of new small-molecule MDM2 inhibitors.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Review
Biochemistry & Molecular Biology
Nicholas McNamee, Ines Pires da Silva, Adnan Nagrial, Bo Gao
Summary: Small-cell lung cancer (SCLC) is an aggressive disease with limited treatment options and poor survival rates. While there have been significant advancements in the treatment of non-small cell lung cancer (NSCLC), SCLC has not seen the same level of progress. This is due, in part, to the complex and heterogeneous nature of SCLC tumors. This review explores the current treatment paradigm of SCLC, recent advances in immunotherapy, challenges in identifying predictive biomarkers, and potential future directions in SCLC treatment research.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Editorial Material
Plant Sciences
Ralf Welsch, Alisher Touraev, Klaus Palme
Summary: The fertilized egg is the starting point for multicellular organism development, plant cells have the ability to regenerate, and the fate of regenerating tissues is regulated by plant hormones.
JOURNAL OF EXPERIMENTAL BOTANY
(2021)
Review
Pharmacology & Pharmacy
Rachel Ringquist, Delta Ghoshal, Ritika Jain, Krishnendu Roy
Summary: The tumor microenvironment (TME) is shaped by dynamic interactions between various cell types, influencing immune responses and therapeutic resistance. Efforts are being made to understand key components and model complexity for studying immunotherapies. Challenges in sourcing and quality control of TME cells persist in developing reproducible platforms for cell therapies.
ADVANCED DRUG DELIVERY REVIEWS
(2021)
Review
Oncology
Hansol Lee, Ines Pires Da Silva, Umaimainthan Palendira, Richard A. Scolyer, Georgina V. Long, James S. Wilmott
Summary: NK cells play a crucial role in the innate immune system and can enhance adaptive immune responses. The activation of NK cells is regulated by a balance of inhibitory and activating receptors. These cells are potent producers of proinflammatory cytokines and can elicit strong antitumor responses through secretion of perforin and granzyme B. Strategies to enhance NK cell responses are being evaluated in clinical trials to improve immunotherapy effectiveness.
Review
Biochemistry & Molecular Biology
Fan Yang, Zhigang Hu, Zhigang Guo
Summary: DNA damage repair is crucial for maintaining genomic stability and integrity, and FEN1 plays a critical role in this process. Abnormal expression or mutation of FEN1 is associated with various diseases, including cancers, making it a therapeutic target for cancer treatment. Small-molecule compounds targeting FEN1 have been developed and show promise in cancer therapy.
Review
Medicine, General & Internal
Jianjing Lin, Shicheng Jia, Weifei Zhang, Mengyuan Nian, Peng Liu, Li Yang, Jianwei Zuo, Wei Li, Hui Zeng, Xintao Zhang
Summary: Osteoarthritis is a degenerative disease characterized by joint pain, caused by factors such as fibrosis, chapping, ulcers, and loss of articular cartilage. Traditional treatments only delay its progression, while small molecule inhibitors targeting proteins show promising effects in managing osteoarthritis. This review examines small molecule inhibitors targeting various proteins and discusses disease-modifying osteoarthritis drugs based on them, providing valuable insights for the treatment of osteoarthritis.
JOURNAL OF CLINICAL MEDICINE
(2023)
Review
Pharmacology & Pharmacy
Yinrong Wu, Zichao Yang, Kui Cheng, Huichang Bi, Jianjun Chen
Summary: Immunotherapy has revolutionized cancer treatment, with current therapies mostly based on antibodies. However, these therapies have limitations in terms of pharmacokinetics and immunogenicity. To overcome these limitations, researchers have focused on developing small molecule-based immunotherapy. This review provides an overview of the progress in small molecule-based immunomodulators for cancer therapy, including targeting PD-1/PD-L1, chemokine receptors, STING, TLR, etc. The importance of combining small molecule-based immunomodulators with therapeutic antibodies is also highlighted.
ACTA PHARMACEUTICA SINICA B
(2022)
Review
Biochemistry & Molecular Biology
Chao Zhang, Qian Xie, Chi Cheong Wan, Zhe Jin, Chun Hu
Summary: HIV-1 integrase plays a crucial role in HIV-1 treatment, but issues like drug resistance require further research. This review discussed the structure, function, and recent advances in small-molecule inhibitors of HIV-1 integrase.
CURRENT MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Melika Loriamini, Melissa M. Lewis-Bakker, Kayluz Frias Boligan, Siming Wang, Mairead B. Holton, Lakshmi P. Kotra, Donald R. Branch
Summary: In our initial publication, we demonstrated that small molecules can inhibit phagocytosis based on in vitro testing of over 200 compounds. We found four hit molecules with pyrazole core structure in a chemical library screening. Further evaluation resulted in the selection of two lead compounds with negligible toxicity and high efficacy in inhibiting phagocytosis. The rational development of these discoveries will lead to the selection of a lead compound(s) for pre-clinical evaluation through independent synthesis and in vivo activities.
Review
Medicine, Research & Experimental
Yingying Lu, Zhijia Li, Shuangqian Zhang, Tongtong Zhang, Yanjun Liu, Lan Zhang
Summary: Cellular mitophagy refers to the process in which cells selectively wrap and degrade damaged mitochondria through autophagy, thus maintaining mitochondrial and intracellular homeostasis. In recent years, mitophagy has gained attention as a research hotspot in the pathogenesis of various clinical diseases. It has been discovered that regulating mitophagy may open up new directions for disease treatment. Additionally, there have been reports of small molecule modulators of mitophagy, providing opportunities to understand the process and potential for therapeutic development.
Article
Chemistry, Medicinal
Yuqin Lei, Qi An, Xiao-Fei Shen, Min Sui, Chungen Li, Da Jia, Youfu Luo, Qingxiang Sun
Summary: The research team successfully designed a noncovalent CRM1 inhibitor with high affinity for human and yeast CRM1 through crystal structure studies, showing superior properties compared to covalent inhibitors. This discovery opens up new avenues for the development of more effective, less toxic, and broad-spectrum anticancer/antiviral therapies.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Zhouling Xie, Xiaoxiao Yang, Yajun Duan, Jihong Han, Chenzhong Liao
Summary: Kinase inhibitors have been successful in treating various diseases beyond cancer, including autoimmune diseases and inflammatory diseases. Several non-oncologic small-molecule kinase inhibitors have been approved, with more in development for different applications.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Editorial Material
Hematology
Debottam Sinha, Rajiv Khanna
Summary: This study introduces a novel multicolor flow cytometry technology to uncover the crucial role of myeloid-derived suppressor cells in EBV-associated lymphoproliferative diseases, with a focus on the proliferation of EBV-positive natural killer (NK) cells and T cells.
Article
Immunology
Mohammed Altaf, Katie E. Lineburg, Pauline Crooks, Sweera Rehan, Katherine K. Matthews, Michelle A. Neller, George R. Ambalathingal, Debottam Sinha, Michelle Grant, Peter M. A. Hopkins, Daniel Chambers, Rajiv Khanna, Corey Smith
Summary: In lung transplant recipients, pretransplant CMV-NIR status is significantly associated with a higher incidence of CMV reactivation posttransplant. Therefore, dysfunctional CMV immunity increases the risk of viral reactivation after transplantation.
JOURNAL OF INFECTIOUS DISEASES
(2021)
Article
Virology
Eunok Lee, Kerrie Sandgren, Gabriel Duette, Vicki V. Stylianou, Rajiv Khanna, John-Sebastian Eden, Emily Blyth, David Gottlieb, Anthony L. Cunningham, Sarah Palmer
Summary: Developing optimal T-cell response assays for SARS-CoV-2 is crucial for measuring immunity duration and vaccine efficacy. By using immunoinformatics analysis, we identified 57 immunogenic peptides with potential global cellular immune response coverage. 18 of these peptides have limited homology to seasonal human coronaviruses, making them promising candidates for specific T-cell immunity tests for SARS-CoV-2. Two peptides elicited effector responses in CD8+ T cells from SARS-CoV-2 convalescent patients.
JOURNAL OF VIROLOGY
(2021)
Correction
Biochemistry & Molecular Biology
Amit Bar-Or, Michael P. Pender, Rajiv Khanna, Lawrence Steinman, Hans-Peter Hartung, Tap Maniar, Ed Croze, Blake T. Aftab, Gavin Giovannoni, Manher A. Joshi
TRENDS IN MOLECULAR MEDICINE
(2021)
Article
Oncology
Debottam Sinha, Sriganesh Srihari, Kirrliee Beckett, Laetitia Le Texier, Matthew Solomon, Archana Panikkar, George R. Ambalathingal, Lea Lekieffre, Pauline Crooks, Sweera Rehan, Michelle A. Neller, Corey Smith, Rajiv Khanna
Summary: Studies have shown that overcoming resistance to in vivo T-cell therapy can be achieved through the sequential infusion of two different allogeneic T-cell therapies restricted by different HLA alleles targeting EBV. Furthermore, the combination of inhibition of the programmed cell death protein-1/programmed death-ligand 1 axis with EBV-specific T-cell therapy significantly improves overall survival in tumor-bearing mice.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2021)
Article
Immunology
Katie E. Lineburg, Emma J. Grant, Srividhya Swaminathan, Demetra S. M. Chatzileontiadou, Christopher Szeto, Hannah Sloane, Archana Panikkar, Jyothy Raju, Pauline Crooks, Sweera Rehan, Andrea T. Nguyen, Lea Lekieffre, Michelle A. Neller, Zhen Wei Marcus Tong, Dhilshan Jayasinghe, Keng Yih Chew, Christian A. Lobos, Hanim Halim, Jacqueline M. Burrows, Alan Riboldi-Tunnicliffe, Weisan Chen, Lloyd D'Orsogna, Rajiv Khanna, Kirsty R. Short, Corey Smith, Stephanie Gras
Summary: Efforts are being made to understand the immune response to SARS-CoV-2, with a focus on T cell immunity and cross-recognition with seasonal coronaviruses. Research has shown that the N protein of SARS-CoV-2 induces an immunodominant response and T cells demonstrate cross-reactivity towards certain coronaviruses through specific peptide conformations.
Article
Oncology
Corey Smith, Margaret McGrath, Michelle A. Neller, Katherine K. Matthews, Pauline Crooks, Laetitia Le Texier, Benedict Panizza, Sandro Porceddu, Rajiv Khanna
Summary: This study presented a novel case report of a patient with metastatic nasopharyngeal carcinoma who was successfully treated with a combination of EBV-specific ACT and PD-1 blockade therapy, resulting in complete resolution of metastatic disease for 22 months. Follow-up immunological analysis showed significant restructuring of the global T-cell repertoire coincident with the clinical response, providing an important platform for further translating these findings to a larger cohort of NPC patients.
NPJ PRECISION ONCOLOGY
(2021)
Article
Peripheral Vascular Disease
Ngar Woon Kam, Ka Chun Wu, Wei Dai, Ying Wang, Leo Yik Chun Yan, Reshma Shakya, Rajiv Khanna, Yanru Qin, Simon Law, Anthony Wing Ip Lo, Victor Ho Fun Lee, Xin-Yuan Guan, Dora Lai-Wan Kwong
Summary: Different functions and profiles of B-cell subsets in various cancers have been reported. In esophageal squamous cell carcinoma (ESCC), proliferating B cells are predominantly found in the peritumoral region with high expression of HMGB1. Cancer-derived HMGB1 modulates B cells to promote angiogenesis in ESCC microenvironment.
Article
Genetics & Heredity
Behnam Rashidieh, Belal Shohayeb, Amanda Louise Bain, Patrick R. J. Fortuna, Debottam Sinha, Andrew Burgess, Richard Mills, Rachael C. Adams, J. Alejandro Lopez, Peter Blumbergs, John Finnie, Murugan Kalimutho, Michael Piper, James Edward Hudson, Dominic C. H. Ng, Kum Kum Khanna
Summary: CEP55 plays a critical role in embryonic development and neural development, with its defects leading to severe clinical manifestations and perinatal lethality. It regulates neural development through the Akt pathway and downstream effector Gsk3 beta, and plays a crucial role in cilia formation.
Article
Microbiology
Vijayendra Dasari, Kirrilee Beckett, Shane Horsefield, George Ambalathingal, Rajiv Khanna
Summary: Researchers have designed a novel bivalent subunit vaccine against CMV, which combines CMV-encoded oligomeric glycoprotein B, polyepitope protein, and a TLR9 agonist to induce both humoral and cellular immune responses. The vaccine generated durable anti-viral antibodies and CMV-specific T cell responses in mice, and showed the potential to prevent CMV-associated complications.
Review
Oncology
Debottam Sinha, Philip Moseley, Xuehan Lu, Quentin Wright, Brian Gabrielli, Ian H. Frazer, Jazmina L. G. Cruz
Summary: Epithelial cancers have high mortality rates, but immunotherapies, particularly immune checkpoint blockade, have emerged as powerful treatment options. However, these cancers are often resistant to immunotherapies, making it crucial to boost their effectiveness. Small molecule inhibitors can target cancer proteins and enhance immune cell performance. This review focuses on using small molecule inhibitors to enhance the efficacy of immune checkpoint blockade.
Article
Immunology
Katie E. Lineburg, Michelle A. Neller, George R. Ambalathingal, Laetitia Le Texier, Jyothy Raju, Srividhya Swaminathan, Lea Lekieffre, Caitlyn Smith, Sweera Rehan, Pauline Crooks, Archana Panikkar, Sriganesh Srihari, Rajiv Khanna, Corey Smith
Summary: This study demonstrates that most recipients of the ChAdOx1-S vaccine generated a T helper 1 response (IFN-gamma and/or IL-2) following the first dose of the vaccine, with a strong correlation between the magnitude of the IFN-gamma and IL-2 response. While some individuals showed production of other cytokines without generating IFN-gamma and IL-2, there was no correlation in magnitude, nor was there a correlation between sex or age and the magnitude of the response.
CLINICAL & TRANSLATIONAL IMMUNOLOGY
(2021)
Meeting Abstract
Cell & Tissue Engineering
D. Sinha, R. Khanna
