Review
Biochemistry & Molecular Biology
Anthony V. Nguyen, Jose M. Soto, Sarah-Marie Gonzalez, Jennifer Murillo, Eric R. Trumble, Frank Y. Shan, Jason H. Huang
Summary: The 2021 World Health Organization Classification of Tumors of the Central Nervous System introduced the H3.3-G34R/V mutant glioma alongside the already recognized H3-K27M altered glioma, reflecting advances in understanding the roles of oncohistones in gliomagenesis. However, the prognosis remains poor for patients with these disease entities and the H3.3-G34R/V mutant gliomas are particularly understudied. Further research is needed to explore the molecular mechanisms underlying gliomagenesis and develop effective diagnosis, treatment, and future therapeutics.
Review
Oncology
M. James Lonie, P. Andrew Barbour, Riccardo Dolcetti
Summary: OAC incidence is rising globally, but current treatment regimens have limited success, highlighting the need for improved immunotherapeutic strategies. Understanding the immune responses to OAC is essential for enhancing therapeutic approaches and potentially improving patient outcomes.
CANCER TREATMENT REVIEWS
(2021)
Review
Immunology
Tiina E. Kahkonen, Jussi M. Halleen, Gary MacRitchie, Ronnie M. Andersson, Jenni Bernoulli
Summary: Bone metastasis is a significant problem in breast, prostate, and other major cancers, causing high mortality and decreased quality of life. Immunotherapies have not been approved for treating bone metastasis, and the current approved immunotherapies show limited effectiveness. Understanding the tumor microenvironment in bone metastasis is crucial for developing novel therapies. The concept of osteoimmuno-oncology (OIO) emphasizes the interactions between tumor, immune, and bone cells, providing potential targets for bone metastasis. This review identifies 24 immunotherapies in preclinical or clinical development with evaluation in bone metastasis, offering insights into immuno-oncology drug development in the context of bone metastasis.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Immunology
Mercedes Beatriz Fuertes, Carolina Ines Domaica, Norberto Walter Zwirner
Summary: Immune checkpoint inhibitors have revolutionized immuno-oncology by achieving durable immune control of cancer, however, tumor immune evasion mechanisms pose a challenge for treatment development. Combination therapies targeting NK cell-activating receptors like NKG2D are emerging as frontrunners in immuno-oncology, with strategies to boost MICA/B expression and inhibit their shedding being proposed for enhancing antitumor immune responses.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Oncology
Sourat Darabi, Joanne Xiu, Timothy Samec, Santosh Kesari, Jose Carrillo, Sonikpreet Aulakh, Kyle M. Walsh, Soma Sengupta, Ashley Sumrall, David Spetzler, Michael Glantz, Michael J. Demeure
Summary: Gliomas are prevalent neurological cancers in the USA, and effective treatment options are limited. Understanding the complex genetic variations and pathway associations of these cancers is crucial for developing new and effective therapies. Mutations in the Capicua gene (CIC) are more common in oligodendroglioma than in low-grade astrocytoma or glioblastoma. CIC mutations are observed in all glioma subtypes, while MAPK-associated mutations are most prevalent in CIC wild-type tissue. However, MAPK activation is enhanced in CIC-mutated oligodendroglioma, highlighting the importance of CIC as a genetic marker for MAPK activation.
Article
Biochemical Research Methods
Pablo Monfort-Lanzas, Raphael Gronauer, Leonie Madersbacher, Christoph Schatz, Dietmar Rieder, Hubert Hackl
Summary: In this study, a user-friendly web platform MIO and a Python toolkit miopy were introduced for visualization and analysis of bulk microRNA and gene expression data, aiming to investigate the potential role of microRNAs in immuno-oncology. The toolkit provides various analysis methods and includes information on 40 microRNA target prediction tools, as well as processed TCGA data and immune-related gene and microRNA signatures.
Review
Biochemistry & Molecular Biology
Xun Xu, Yuan Liang, Ilgiz Gareev, Yanchao Liang, Rui Liu, Ning Wang, Guang Yang
Summary: This review discusses the crucial role of lncRNA in glioma, its value as a biomarker for diagnosis and prognosis, and the feasibility of using lncRNA as therapeutic targets. The article concludes with the current deficiencies and future prospects in utilizing lncRNA as clinical biomarkers and therapeutic targets.
MOLECULAR BIOLOGY REPORTS
(2023)
Review
Medicine, Research & Experimental
Gustav van Niekerk, Angus G. Dalgleish, Fourie Joubert, Annie Joubert, Anna-Mart Engelbrecht
Summary: Insulin regulates immune cell phenotypes through the PI3K/Akt/mTOR pathway, potentially impacting ICB therapy; Insulin interacts with immune pathways such as JAK/STAT, and is regulated by PD-1 and CTLA-4.
Review
Cell Biology
Xin Wang, Xu Wang, Midie Xu, Weiqi Sheng
Summary: Long noncoding RNAs (lncRNAs) play a crucial role in cancer development by impacting the tumor microenvironment through chromatin remodeling, transcriptional and post-transcriptional regulation. Additionally, the function of lncRNAs in immune recognition and evasion in tumor-infiltrating immune cells has raised significant interest in immuno-oncology.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Review
Pharmacology & Pharmacy
Christine Grimaldi, Alex Ibraghimov, Andrea Kiessling, Benno Rattel, Changhua Ji, Claudette L. Fuller, Frank R. Brennan, Franziska Regenass-Lechner, Jacintha Shenton, Karen D. Price, Marie-Soleil Piche, Meredith A. Steeves, Rodney Prell, Sherri Dudal, Sven Kronenberg, Wendy Freebern, Diann Blanset
Summary: Harnessing the immune system to kill tumors has revolutionized cancer treatment, but it can also lead to adverse events that pose safety risks. This article reviews the biology and mechanisms of immune-mediated adverse effects and discusses industry approaches for nonclinical safety risk assessments in immune-oncology.
DRUG DISCOVERY TODAY
(2023)
Article
Oncology
Milana Bergamino Sirven, Sonia Pernas, Maggie C. U. Cheang
Summary: The introduction of immunotherapy has revolutionized cancer treatment, but brings opportunities and challenges. For successful development of promising IO drugs, key areas such as trial designs, surrogate endpoints, biomarkers, toxicity monitoring, and collaborative approaches need to be redefined. These aspects are crucial for optimizing outcomes and accelerating approvals in immuno-oncology.
Review
Biochemistry & Molecular Biology
Maria A. Boylan, Andrew Pincetic, Gary Romano, Nadine Tatton, Sara Kenkare-Mitra, Arnon Rosenthal
Summary: Immuno-neurology is an emerging therapeutic strategy for dementia and neurodegeneration that aims to address immune surveillance failure in the brain. By modulating the function of microglia and enhancing immune activity, it has the potential to counteract various disease pathologies and revolutionize the treatment of neurodegenerative disorders.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Juliana Sitta, Pier Paolo Claudio, Candace M. Howard
Summary: Immunotherapy has shown promising results in certain types of cancer, but the immune suppression mechanisms of tumors limit its efficacy. Oncolytic viruses, as a novel therapeutic approach, can enhance immune response and improve treatment outcomes through genetic engineering. However, developing preclinical models that replicate human immune response remains a challenge.
Article
Multidisciplinary Sciences
Ellis L. Reinherz, Wonmuk Hwang, Matthew J. Lang
Summary: T cell receptors (TCR) on cytolytic T lymphocytes (CTLs) recognize foreign antigens bound in the groove of major histocompatibility complex (MHC) molecules (H-2 in mouse and HLA in human) displayed on altered cells. Mechanobiology optimizes TCR specificity and sensitivity by applying mechanical load to the bond formed between TCR and pMHC ligand. Applying TCR mechanobiology to T cell monitoring and treatment can improve cancer vaccine development and immunotherapy paradigms.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Medicine, Research & Experimental
Agathe Dubuisson, Jean-Eudes Fahrner, Anne-Gaelle Goubet, Safae Terrisse, Nicolas Voisin, Charles Bayard, Sebastien Lofek, Damien Drubay, Delphine Bredel, Severine Mouraud, Sandrine Susini, Alexandria Cogdill, Lucas Rebuffet, Elise Ballot, Nicolas Jacquelot, Vincent Thomas de Montpreville, Odile Casiraghi, Camelia Radulescu, Sophie Ferlicot, David J. Figueroa, Sapna Yadavilli, Jeremy D. Waight, Marc Ballas, Axel Hoos, Thomas Condamine, Bastien Parier, Christophe Gaudillat, Bertrand Routy, Francois Ghiringhelli, Lisa Derosa, Ingrid Breuskin, Mathieu Rouanne, Fabrice Andre, Cedric Lebacle, Herve Baumert, Marie Wislez, Elie Fadel, Isabelle Cremer, Laurence Albiges, Birgit Geoerger, Jean-Yves Scoazec, Yohann Loriot, Guido Kroemer, Aurelien Marabelle, Melodie Bonvalet, Laurence Zitvogel
Summary: Decision making in immuno-oncology plays a crucial role in adapting therapy to the tumor microenvironment. A multiplex functional and dynamic immuno-assay has been developed to predict unresponsiveness to anti-PD-1 mAbs and detect personalized combinatorial regimens in human primary tumors, awaiting validation in prospective clinical trials.
EMBO MOLECULAR MEDICINE
(2021)
Review
Pharmacology & Pharmacy
Fatih M. Uckun, Saran Saund, Hitesh Windlass, Vuong Trieu
Summary: Artemisinin, an anti-inflammatory plant medicine originally used for anti-malarial purposes, has been repurposed as a potential drug for COVID-19. It inhibits early infection processes and disrupts viral replication, while also reducing inflammatory cytokines to prevent worsening of COVID-19 patients.
FRONTIERS IN PHARMACOLOGY
(2021)
Review
Oncology
Fatih M. Uckun
Summary: This article provides a comprehensive review of new and emerging treatment strategies against multiple myeloma, including precision medicines and drugs that improve the immune system. These new treatment methods have the potential to change the therapeutic landscape in multiple myeloma and improve long-term survival outcomes for patients.
Article
Cell Biology
Fatih M. Uckun, Taracad Venkatachalam
Summary: Repurposing FDA-approved BTK inhibitors as therapeutic agents for solid tumors could provide renewed hope for chemotherapy-resistant cancer patients. Emerging evidence suggests that BTK inhibitors have clinical potential in solid tumor therapy and may lead to the development of new and effective combination regimens for metastatic and/or therapy-refractory solid tumor patients through lead optimization and translational research.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Medicine, Research & Experimental
Fatih M. Uckun, Cemal Orhan, Joy Powell, Emre Sahin, Ibrahim H. Ozercan, Michael Volk, Kazim Sahin
Summary: The study demonstrated that two distinct formulations of the anti-sepsis drug candidate Rejuveinix have favorable safety profiles in Wistar Albino rats at dose levels comparable to projected clinical doses. Both formulations elevated tissue levels of the antioxidant enzyme superoxide dismutase and ascorbic acid in a dose-dependent manner and showed protective activity in a mouse model of sepsis. Additionally, both RJX-P and RJX-B exhibited near-identical potent and dose-dependent anti-oxidant and anti-inflammatory activity in a mouse model of ARDS and multi-organ failure.
BIOMEDICINE & PHARMACOTHERAPY
(2021)
Article
Oncology
Fatih M. Uckun, Justin Watts, Alice S. Mims, Prapti Patel, Eunice Wang, Paul J. Shami, Elizabeth Cull, Cynthia Lee, Christopher R. Cogle, Tara L. Lin
Summary: The study evaluated the risk, characteristics, and biomarkers of cytokine release syndrome (CRS) in patients receiving APVO436 for relapsed/refractory acute myeloid leukemia (AML) or myelodysplastic syndrome. CRS incidence was not influenced by dose level, gender, race, obesity, or hematologic parameters, but age may play a role in CRS development.
Review
Oncology
Fatih M. Uckun
Summary: T-cell engaging bispecific antibodies (BsABs) have the potential to delay disease progression in multiple myeloma by redirecting host T-cell cytotoxicity towards malignant MM clones and immunosuppressive myeloid-derived suppressor cells in the bone marrow microenvironment.
FRONTIERS IN ONCOLOGY
(2021)
Article
Oncology
Justin Watts, Tara L. Lin, Alice Mims, Prapti Patel, Cynthia Lee, Anoush Shahidzadeh, Paul Shami, Elizabeth Cull, Christopher R. Cogle, Eunice Wang, Fatih M. Uckun
Summary: APVO436 is a recombinant bispecific antibody that could be used to treat hematologic malignancies, particularly relapsed or refractory AML/MDS patients. Preliminary clinical trial results showed promising tolerability and activity of APVO436 in these patients, with activation of T cells.
FRONTIERS IN ONCOLOGY
(2022)
Article
Oncology
Deniz C. Guven, Taha K. Sahin, Serkan Akin, Fatih M. Uckun
Summary: Patients with hematologic malignancies, especially those with CLL and those receiving specific treatments, have significantly lower seroconversion rates after SARS-CoV-2 vaccination. Effective strategies are urgently needed to improve vaccine efficacy in these vulnerable populations.
Article
Microbiology
Fatih M. Uckun, Muhammad Saeed, Mustafa Awili, Ibrahim H. Ozercan, Sanjive Qazi, Cynthia Lee, Adeel Shibli, Alan W. Skolnick, Alonso Prusmack, Joseph Varon, Cesar I. P. Barrera, Cemal Orhan, Michael Volk, Kazim Sahin
Summary: This study compared the effects of Rejuveinix, dexamethasone, and their combination on fatal sepsis in an animal model and COVID-19 patients. The results showed that RJX exhibited potent anti-inflammatory activity, reducing cytokine responses and organ damage in mice, and improving survival outcome. The clinical study also demonstrated that RJX plus DEX was well tolerated by COVID-19 patients.
FUTURE MICROBIOLOGY
(2022)
Letter
Oncology
Deniz C. Guven, Taha K. Sahin, Serkan Akin, Fatih M. Uckun
Article
Oncology
Fatih M. Uckun, Sanjive Qazi, Vuong Trieu
Summary: This study evaluated the clinical significance of amplified expression levels of transforming growth factor beta 2 (TGFB2) in tumor tissue specimens from pediatric DIPG patients. The results showed that high level TGFB2 expression is associated with poor treatment outcome in DIPG. These findings support further evaluation of new strategies targeting TGFB2 in pediatric DIPG.
Article
Oncology
Sanjive Qazi, Fatih M. Uckun
Summary: This study evaluated the clinical significance of CD22 exon 12 deletion and found that it is associated with poor treatment outcomes in B-ALL. The results suggest that further evaluation of targeting this abnormality in B-ALL is warranted.
Article
Health Care Sciences & Services
Sanjive Qazi, Fatih M. Uckun
Summary: We investigated the expression of ErbB family protein tyrosine kinases, including ERBB1, at the transcript level in primary malignant lymphoma cells from 498 adult patients with diffuse large B-cell lymphoma (DLBCL). The expression of ERBB1 in DLBCL cells was significantly higher compared to normal B-lineage lymphoid cells. Increased ERBB1 mRNA expression in DLBCL cells was correlated with amplified expression of transcription factors that recognize ERBB1 gene promoter sites. Importantly, amplified ERBB1 expression in DLBCL and its subtypes was associated with significantly worse overall survival (OS). These findings support further evaluation of the prognostic significance of high-level ERBB1 mRNA expression and the clinical potential of personalized medicines targeting ERBB1 in high-risk DLBCL.
JOURNAL OF PERSONALIZED MEDICINE
(2023)
Article
Oncology
Fatih M. Uckun, Tara L. Lin, Alice S. Mims, Prapti Patel, Cynthia Lee, Anoush Shahidzadeh, Paul J. Shami, Elizabeth Cull, Christopher R. Cogle, Justin Watts
Summary: This study evaluated a new therapy for AML patients who had failed standard treatment options. The therapy, APVO436, showed favorable safety and preliminary evidence of efficacy, indicating the need for further investigation into its clinical impact potential.