Article
Oncology
Kathleen M. Mahoney, Petra Ross-Macdonald, Long Yuan, Linan Song, Eliseo Veras, Megan Wind-Rotolo, David F. McDermott, F. Stephen Hodi, Toni K. Choueiri, Gordon J. Freeman
Summary: This study investigated the levels of soluble PD-L1 (sPD-L1) before and during nivolumab treatment in metastatic clear cell renal cell carcinoma (RCC) and melanoma patients. The results showed that sPD-L1 levels were associated with worse prognosis and clinical factors. Additionally, changes in sPD-L1 levels during treatment were linked to treatment outcomes.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Article
Oncology
Richard S. P. Huang, Karthikeyan Murugesan, Meagan Montesion, Dean C. Pavlick, Douglas A. Mata, Matthew C. Hiemenz, Brennan Decker, Garrett Frampton, Lee A. Albacker, Jeffrey S. Ross
Summary: The study analyzed a large cohort of solid tumor cases to investigate CD274 copy-number changes and their correlation with PD-L1 protein expression. The prevalence of CD274 copy-number changes varied across different tumor types and was found to be significantly associated with PD-L1 positivity in certain tumor types, indicating its potential as a biomarker for immune checkpoint inhibitor therapy.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2021)
Article
Oncology
Richard S. P. Huang, Brennan Decker, Karthikeyan Murugesan, Matthew Hiemenz, Douglas A. Mata, Gerald Li, James Creeden, Shakti H. Ramkissoon, Jeffrey S. Ross
Summary: The study found low prevalence of non-amplification short variants (SV) mutations in CD274, with mutation types and rates varying by tumor type. Specific mutation types may affect the expression level of PD-L1 protein and potentially function as resistance biomarkers in ICPI therapy.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2021)
Article
Chemistry, Multidisciplinary
Connie Wu, Tyler J. Dougan, David R. Walt
Summary: A major challenge in clinical diagnostic applications is measuring low-abundance proteins and biomolecules. We developed a more sensitive and streamlined digital ELISA platform called MOSAIC, which achieves attomolar limits of detection and has an order of magnitude improvement in sensitivity compared to other methods. MOSAIC uses rapid and automatable flow cytometric readout, increasing throughput and easily integrating into existing laboratory infrastructure. We demonstrated the attomolar sensitivity, high throughput, and broad multiplexing capabilities of MOSAIC by detecting low-abundance cytokines in saliva and performing ultrasensitive multiplexed measurements of protein analytes in plasma and saliva.
Article
Immunology
Shayista Akbar, Afsheen Raza, Reyad Mohsin, Aladdin Kanbour, Shahnaz Qadri, Aijaz Parray, Abdul Rehman Zar Gul, Anite Philip, Suma Vijayakumar, Maysaloun Merhi, Shereena Hydrose, Varghese Philipose Inchakalody, Rajaa Al-Abdulla, Wafa Abualainin, Shaza Abu Sirriya, Issam Al-Bozom, Shahab Uddin, Omar Muhammad Khan, Mohamed Izham Mohamed Ibrahim, Ussama Al Homsi, Said Dermime
Summary: This study evaluated the levels of 27 serum-derived exosomal immuno-oncological proteins and 44 cytokines/chemokines in NSCLC patients before and after ICIs therapy, in order to identify surrogate biomarkers for treatment response and monitoring. The results showed that exosomal immuno-oncological proteins/cytokines can be potential biomarkers to predict the clinical outcomes and monitor response to ICIs therapy in NSCLC patients.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Oncology
Fatima Abdullahi Sidi, Victoria Bingham, Stephanie G. Craig, Stephen McQuaid, Jacqueline James, Matthew P. Humphries, Manuel Salto-Tellez
Summary: The study demonstrates the usefulness of advanced computer software in helping pathologists assess routine tests for immunotherapy treatment. Multiplex testing can provide specific information from patient samples. The use of multiplex immunofluorescence and digital image analysis is effective in quantifying PD-L1 in non-small cell lung cancer and supports clinical workflows.
Article
Biochemical Research Methods
Mahmoud Elsabahy, Karen L. Wooley, Amy Hendricksen, Kenneth Oh
Summary: A robust data mining algorithm is presented as a critical solution to managing data from multiplexing techniques, allowing simultaneous detection of multiple biomarkers in a single sample. This algorithm has been successfully applied as a diagnostic and therapeutic monitoring tool in managing breast cancer.
Review
Pharmacology & Pharmacy
Jinhua Liu, Zichao Chen, Yaqun Li, Wenjie Zhao, JiBiao Wu, Zhen Zhang
Summary: Programmed death protein 1 (PD1) is an important immune checkpoint on T cells that plays a crucial role in downregulating the immune system and promoting self-tolerance, while its ligand, programmed cell death ligand 1 (PDL1), is overexpressed in malignant tumor cells, contributing to immune evasion and treatment failure. Despite the clinical efficacy of PD1/PDL1 inhibitors in many tumors, some patients may develop drug resistance, highlighting the need for further research into improving targeted therapies and understanding the associated safety issues.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Oncology
Alexander Stein, Donjete Simnica, Christoph Schultheiss, Rebekka Scholz, Joseph Tintelnot, Eray Goekkurt, Lisa von Wenserski, Edith Willscher, Lisa Paschold, Markus Sauer, Sylvie Lorenzen, Jorge Riera-Knorrenschild, Reinhard Depenbusch, Thomas J. Ettrich, Steffen Doerfel, Salah-Eddin Al-Batran, Meinolf Karthaus, Uwe Pelzer, Lisa Waberer, Axel Hinke, Marcus Bauer, Chiara Massa, Barbara Seliger, Claudia Wickenhauser, Carsten Bokemeyer, Susanna Hegewisch-Becker, Mascha Binder
Summary: In MSS mCRC patients, immune checkpoint blockade is ineffective, but combining avelumab with standard treatment appears safe and feasible. PD-L1 mutations mediate subclonal immune escape to avelumab, particularly in patients expressing high-affinity Fc gamma R3a, leading to enhanced T cell killing and limiting subclonal expansion. Further trials evaluating the addition of avelumab in this patient subgroup are warranted.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2021)
Article
Oncology
Denis Leonardo Jardim, Karthikeyan Murugesan, Julia A. Elvin, Richard S. P. Huang, Razelle Kurzrock
Summary: PD-L1 (CD274) amplification level and focality have an impact on PD-L1 protein expression. PD-L1 amplification was detected using a comparative genomic hybridization-like method and PD-L1 protein expression was analyzed by immunohistochemistry (IHC) using the DAKO 22C3 antibody. A total of 60,793 samples were analyzed, with the most common histologies being lung adenocarcinoma (20%), colon adenocarcinoma (12%), and lung squamous carcinoma (8%). The study found that 1.21% of tumors (738/60,793) had PD-L1 amplification. Focality categories ranged from <0.1 mB (2.4%) to >= 20 mB (24.4%). Lower levels of PD-L1 amplification were more frequently non-focal, while more focal amplifications correlated with higher PD-L1 IHC expression. The median tumor proportion score (TPS) for PD-L1 amplified samples according to focality ranged from 87.5% (<0.1 mB) to 1% (>= 20mB). In conclusion, PD-L1 protein expression is influenced by the level and focality of PD-L1 amplification.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2023)
Article
Oncology
Sen Yan, Han Zeng, Kaifeng Jin, Fei Shao, Zhaopei Liu, Yuan Chang, Yiwei Wang, Yu Zhu, Zewei Wang, Le Xu, Jiejie Xu
Summary: The expression of NKG2A and PD-L1 together can be used as a combinatorial biomarker to predict the therapeutic response to immune checkpoint blockade in patients with muscle-invasive bladder cancer.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Review
Immunology
Meng Chen, Chenyan Li, Mingjun Sun, Yiling Li, Xuren Sun
Summary: This review summarizes the challenges in the treatment of gastroesophageal cancers (GECs) and the use of immune checkpoint inhibitors as a new therapeutic approach. Ongoing clinical trials with PD-1/PD-L1 pathway blockers in GEC are discussed, and further research is needed to apply them in the clinical care of patients. The review provides insights into the efficacy of PD-1/PD-L1 antibodies as a first-line treatment and in second-line or more treatment for GEC.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Oncology
Andrew D. Kelly, Karthikeyan Murugesan, Zheng Kuang, Meagan Montesion, Jeffrey S. Ross, Lee A. Albacker, Richard S. P. Huang, Douglas Lin, Umut Demirci, James Creeden
Summary: CD274 gene rearrangements are associated with increased PD-L1 immunohistochemistry scores, higher tumor mutational burden, and potential clinical benefit in patients with cancer receiving ICI treatment.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2021)
Review
Oncology
Mengke Niu, Ming Yi, Ning Li, Suxia Luo, Kongming Wu
Summary: Immunotherapy, particularly anti-PD-1/PD-L1 treatment, has shown significant improvements in the survival of NSCLC patients, although the overall response rate remains suboptimal. Various factors influence treatment outcomes, indicating the importance of exploring biomarkers to better select patients and predict treatment efficacy accurately.
EXPERIMENTAL HEMATOLOGY & ONCOLOGY
(2021)
Article
Chemistry, Physical
Lin Zhu, Yuanfeng Xu, Siyin Kang, Bingqian Lin, Chi Zhang, Zhenlong You, Haoting Lin, Chaoyong Yang, Yanling Song
Summary: A new method for precise quantitation of glycosylated exoPD-L1 has been developed in this study, which allows for high sensitivity and selectivity in distinguishing the levels of glycosylated exoPD-L1 between healthy donors and cancer patients without the need for washing. Compared to the total circulating exoPD-L1 level, glycosylated exoPD-L1 is identified for the first time as a more reliable biomarker for tumor diagnosis.
Article
Oncology
Matthias Osswald, Jonas Blaes, Yunxiang Liao, Gergely Solecki, Miriam Goemmel, Anna S. Berghoff, Laurent Salphati, Jeffrey J. Wallin, Heidi S. Phillips, Wolfgang Wick, Frank Winkler
CLINICAL CANCER RESEARCH
(2016)
Article
Chemistry, Medicinal
Timothy P. Heffron, Robert A. Heald, Chudi Ndubaku, BinQing Wei, Martin Augistin, Steven Do, Kyle Edgar, Charles Eigenbrot, Lori Friedman, Emanuela Gancia, Philip S. Jackson, Graham Jones, Aleksander Kolesnikov, Leslie B. Lee, John D. Lesnick, Cristina Lewis, Neville McLean, Mario Moertl, Jim Nonomiya, Jodie Pang, Steve Price, Wei Wei Prior, Laurent Salphati, Steve Sideris, Steven T. Staben, Stefan Steinbacher, Vickie Tsui, Jeffrey Wallin, Deepak Sampath, Alan G. Oliver
JOURNAL OF MEDICINAL CHEMISTRY
(2016)
Review
Oncology
Priti S. Hegde, Jeffrey J. Wallin, Christoph Mancao
SEMINARS IN CANCER BIOLOGY
(2018)
Article
Oncology
Stephen V. Liu, D. Ross Camidge, Scott N. Gettinger, Giuseppe Giaccone, Rebecca S. Heist, F. Stephen Hodi, Neal E. Ready, Wei Zhang, Jeffrey Wallin, Roel Funke, Daniel Waterkamp, Paul Foster, Koho Iizuka, John Powderly
EUROPEAN JOURNAL OF CANCER
(2018)
Article
Immunology
Sharon A. Riddler, Michael Para, Constance A. Benson, Anthony Mills, Moti Ramgopal, Edwin DeJesus, Cynthia Brinson, Joshua Cyktor, Jana Jacobs, Dianna Koontz, John W. Mellors, Gregory M. Laird, Terri Wrin, Heena Patel, Susan Guo, Jeffrey Wallin, Jillian Boice, Liao Zhang, Rita Humeniuk, Rebecca Begley, Polina German, Hiba Graham, Romas Geleziunas, Diana M. Brainard, Devi SenGupta
Summary: In a Phase Ib study investigating the effects of vesatolimod in adults with HIV-1, the drug was found to be generally well tolerated and immune stimulation was observed at doses above 4 mg, indicating potential for future combination trials in individuals living with HIV.
CLINICAL INFECTIOUS DISEASES
(2021)
Article
Gastroenterology & Hepatology
Edward J. Gane, Hyung Joon Kim, Kumar Visvanathan, Yoon Jun Kim, Anh-Hoa Nguyen, Jeffrey J. Wallin, Diana Y. Chen, Circe McDonald, Priyanka Arora, Susanna K. Tan, Anuj Gaggar, Stuart K. Roberts, Young-Suk Lim
Summary: Selgantolimod was found to be safe and well-tolerated in patients with chronic hepatitis B (CHB), inducing cytokine responses and antiviral immunity. Although some patients experienced adverse events and laboratory abnormalities, they were mild or moderate in severity. Further studies with longer treatment durations are needed to assess efficacy.
Article
Virology
Minchao Li, Jinfeng Zeng, Ruiting Li, Ziyu Wen, Yanhui Cai, Jeffrey Wallin, Yuelong Shu, Xiangjun Du, Caijun Sun
Summary: Developing a global HCoVs vaccine is crucial in the field of public health with the rapid spread of COVID-19. The novel antigen design with broad coverage has the potential to induce strong CTL responses.
Article
Cell Biology
Devi SenGupta, Cynthia Brinson, Edwin DeJesus, Anthony Mills, Peter Shalit, Susan Guo, Yanhui Cai, Jeffrey J. Wallin, Liao Zhang, Rita Humeniuk, Rebecca Begley, Romas Geleziunas, John Mellors, Terri Wrin, Norman Jones, Jeffrey Milush, April L. Ferre, Barbara L. Shacklett, Greg M. Laird, Brian Moldt, Elena Vendrame, Diana M. Brainard, Moti Ramgopal, Steven G. Deeks
Summary: TLR7 agonist vesatolimod, when combined with ART, showed potential to delay viral rebound in HIV-1-infected controllers by reducing intact proviral DNA levels at the end of treatment. Further larger clinical studies are needed to evaluate the efficacy of vesatolimod-based combination therapies for long-term control of HIV infection.
SCIENCE TRANSLATIONAL MEDICINE
(2021)
Article
Oncology
Kyung W. Song, Kyle A. Edgar, Emily J. Hanan, Marc Hafner, Jason Oeh, Mark Merchant, Deepak Sampath, Michelle A. Nannini, Rebecca Hong, Lilian Phu, William F. Forrest, Eric Stawiski, Stephen Schmidt, Nicholas Endres, Jane Guan, Jeffrey J. Wallin, Jonathan Cheong, Emile G. Plise, Gail D. Lewis Phillips, Laurent Salphati, Timothy P. Heffron, Alan G. Olivero, Shiva Malek, Steven T. Staben, Donald S. Kirkpatrick, Anwesha Dey, Lori S. Friedman
Summary: The PI3K inhibitors GDC-0077 and taselisib have a unique mechanism of action by degrading mutant p110a protein, leading to more potent inhibition of mutant PI3K pathway signaling and cell viability, and better maintenance of prolonged pathway suppression.
Article
Immunology
Natarajan Ayithan, Lydia Tang, Susanna K. Tan, Diana Chen, Jeffrey J. Wallin, Simon P. Fletcher, Shyam Kottilil, Bhawna Poonia
Summary: TLR8 activation enhances follicular helper T cell function, leading to improved B cell response in chronic hepatitis B infection. TLR8 agonists may promote monocyte-mediated T-FH function and enhance HBV-specific B cell responses, potentially playing a role in achieving HBV functional cure.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Virology
Natarajan Ayithan, Alip Ghosh, Ankit Dwivedi, Jeffrey J. Wallin, Susanna K. Tan, Diana Chen, Shyam Kottilil, Bhawna Poonia
Summary: This study demonstrates that administration of selgantolimod in healthy individuals leads to alterations in immune cell populations, including monocytes, activated dendritic cells, mucosal-associated invariant T cells, and lymphoid cells. The changes in these cell frequencies and molecular expression suggest potential migration of different cell types in response to the agonist, highlighting the activation of multiple immune cell responses with antiviral potential.
Article
Pharmacology & Pharmacy
Rajbharan Yadav, Siddharth Sukumaran, Tanja S. Zabka, Jinze Li, Amy Oldendorp, Gary Morrow, Arthur Reyes, Melissa Cheu, Jessica Li, Jeffrey J. Wallin, Siao Tsai, Laura Sun, Peiyin Wang, Diego Ellerman, Christoph Spiess, Andy Polson, Eric G. Stefanich, Amrita Kamath, Meric A. Ovacik
Summary: The study focuses on the impact of CD3 binding affinity on the pharmacokinetics of T cell-dependent bispecific antibodies. The results demonstrate that CD3 binding affinity affects the clearance rate of the antibody and may be related to the internalization rate of CD79b and the binding ability of CD3.
Article
Gastroenterology & Hepatology
Edward J. Gane, P. Rod Dunbar, Anna E. Brooks, Fangqiu Zhang, Diana Chen, Jeffrey J. Wallin, Nicholas van Buuren, Priyanka Arora, Simon P. Fletcher, Susanna K. Tan, Jenny C. Yang, Anuj Gaggar, Shyamasundaran Kottilil, Lydia Tang
Summary: Selgantolimod treatment showed positive effects on hepatitis B surface antigen, but only a few patients achieved the primary efficacy endpoint. The common adverse events during treatment included nausea, upper respiratory tract infection, and vomiting. Overall, this treatment approach showed potential in a small proportion of patients.
JOURNAL OF HEPATOLOGY
(2023)
Article
Medicine, Research & Experimental
David Z. Pan, Pamela M. Odorizzi, Andre Schoenichen, Mazin Abdelghany, Shuguang Chen, Anu Osinusi, Scott D. Patterson, Bryan Downie, Kavita Juneja, Jeffrey J. Wallin
Summary: This study assessed the impact of RDV treatment on biomarkers in COVID-19 patients. The findings indicate that RDV treatment can accelerate the improvement of multiple biomarkers associated with COVID-19 severity, leading to better clinical outcomes.
COMMUNICATIONS MEDICINE
(2023)
Article
Gastroenterology & Hepatology
Nicholas van Buuren, Ricardo Ramirez, Scott Turner, Diana Chen, Vithika Suri, Abhishek Aggarwal, Christina Moon, Sam Kim, Dmytro Kornyeyev, Nam Bui, Neeru Bhardwaj, Henry Ly Chan, Patrick Marcellin, Maria Buti, Jeffrey Wallin, Anuj Gaggar, Simon P. Fletcher, Lauri Diehl, Li Li, Hongmei Mo, Becket Feierbach
Summary: By analyzing liver biopsies from patients with chronic HBV infection using RNA-Seq and a custom multiplex immunofluorescence panel, two distinct liver immune microenvironments were identified as immune high and immune low. Patients with immune high status exhibited elevated immune pathways and increased presence of immune cells.
