Article
Oncology
Kathryn M. Appleton, Ashley K. Elrod, Katy A. Lassahn, Stephen Shuford, Lillia M. Holmes, Teresa M. DesRochers
Summary: This study examined the effectiveness of using three-dimensional (3D) spheroids to detect patient-specific immune-related activity in ovarian cancer. It found that some patients had higher sensitivity to immune checkpoint inhibitors and demonstrated increases in cytotoxic T cell activation and DC major histocompatibility complex (MHC) class-II expression upon cytokine stimulation. Ex vivo 3D spheroid platforms accurately detected immune cell activity and modulation, providing evidence for their utility in showing sensitivity to ICIs alone or in combination with PARP-Is in a preclinical setting.
CANCER IMMUNOLOGY IMMUNOTHERAPY
(2021)
Article
Oncology
Taigo Kato, Kazuma Kiyotani, Eisuke Tomiyama, Yoko Koh, Makoto Matsushita, Yujiro Hayashi, Kosuke Nakano, Yu Ishizuya, Cong Wang, Koji Hatano, Atsunari Kawashima, Takeshi Ujike, Kazutoshi Fujita, Norio Nonomura, Motohide Uemura
Summary: In this study, researchers analyzed peripheral blood and tumor tissue samples from patients with advanced kidney cancer before and after PD-1 treatment and found an expansion of specific T cell clones in the peripheral blood of responders post-treatment, indicating a possible correlation with tumor-infiltrating T cells.
Article
Chemistry, Applied
Qian Wang, Hao Jiang, Hongli Zhang, Weiqiao Lu, Xiao Wang, Wenfeng Xu, Jia Li, Youjing Lv, Guoyun Li, Chao Cai, Guangli Yu
Summary: This study proposes a novel strategy of antibody-beta-glucan conjugates (AGC) to enhance the antitumor immune response to immune checkpoint blockade (ICB) therapy. AGC demonstrated powerful tumor suppression and promoted interaction between tumor cells and dendritic cells (DCs), thereby enhancing immunotherapeutic benefits.
CARBOHYDRATE POLYMERS
(2024)
Article
Multidisciplinary Sciences
Jingxin Liu, Qiang Zheng, Xiao Mu, Yanfei Zuo, Bo Xu, Yan Jin, Yue Wang, Hua Tian, Yongguo Yang, Qianqian Xue, Ziling Huang, Lijun Chen, Bin Gu, Xianxu Hou, Linlin Shen, Yan Guo, Yuan Li
Summary: The study introduced a new automated tumor scoring system to evaluate PD-L1 expression, showing high consistency with pathologists' scores and providing a powerful tool for pathologists.
SCIENTIFIC REPORTS
(2021)
Article
Endocrinology & Metabolism
Pauline C. Xu, Yi Luan, Seok-Yeong Yu, Jing Xu, Donald W. Coulter, So-Youn Kim
Summary: Immunotherapy has become a cutting-edge approach in cancer treatment. In this study, the effects of PD-1 immune checkpoint blockade on the ovarian reserve were investigated using female mice models. The results suggest that PD-1 blockade may affect the ovarian reserve through a mechanism involving inflammation, but it has no impact on short-term fertility.
JOURNAL OF ENDOCRINOLOGY
(2022)
Article
Immunology
Jin Shang, Lin Li, Chunyou Lai, Tianhang Feng, Yutong Yao, Deyuan Zhong, Yuxin Liang, Xiaolun Huang, Qinyan Yang, Ying Shi
Summary: In this study, we analyzed single-cell transcriptome data from NSCLC patients receiving anti-PD-1 treatment. We identified 6 distinct clusters of NK cells in the infiltrating immune cells of NSCLC. It was found that the responsive group had an enrichment of immature NK cells. Marker genes of immature NK cells were associated with anti-PD-1 response and immune regulation processes. Additionally, effector CD8+ T cells were significantly enriched in the responsive group and showed interactions with immature NK cells. The expression of CXCR4 was associated with infiltration of CD8+ T cells.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2023)
Article
Medicine, Research & Experimental
Guangyuan Li, Susmita Ghosh, JuMe Park, Hyunsu Shin, Mamatha Garige, Gregory Reaman, Carole Sourbier
Summary: ICIs have revolutionized the treatment of cancer patients, but a rare and severe immune-related endocrinopathy called diabetes is associated with this therapy. This study investigated the role of glycosylation in the development of IC-mediated diabetes and the evaluation of different ICIs' physiological effects on pancreatic cells using a mouse pancreatic organoid model. The findings suggest that modulation of ICI glycosylation can alter their metabolic effects on pancreatic cells, and this model can be used for monitoring and comparing ICIs, as well as studying the underlying mechanisms of IC-mediated diabetes.
Article
Pediatrics
Aditi Dasgupta, Eric Tsay, Noah Federman, Melissa G. Lechner, Maureen A. Su
Summary: Use of immune checkpoint inhibitors (ICI) is increasing in children, prompting the need for prompt recognition and management of associated immune-related adverse events (IRAEs). The pattern and management guidelines of IRAEs in children are currently unclear.
Article
Chemistry, Medicinal
Yiqiang OuYang, Jian Gao, Lei Zhao, Junfeng Lu, Haiqing Zhong, Hua Tang, Shuanglong Jin, Lu Yue, Yuezhen Li, Wenjie Guo, Qiang Xu, Yisheng Lai
Summary: The newly designed compound B2 is a promising PD-1/PD-L1 inhibitor with potent anticancer activity and plays an important role in antitumor immunity.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Review
Biochemistry & Molecular Biology
Hao Zhang, Lin Liu, Jinbo Liu, Pengyuan Dang, Shengyun Hu, Weitang Yuan, Zhenqiang Sun, Yang Liu, Chengzeng Wang
Summary: In recent years, tumor immunotherapy, especially immune checkpoint inhibitors, has shown significant progress. However, these treatments are only effective for a small proportion of patients with solid cancers. Tumor-associated macrophages play a crucial role in the tumor microenvironment and have been shown to impact the therapeutic effect of PD-1/PD-L1 inhibitors.
Article
Oncology
Akiko Matsumoto, Chiho Nakashima, Shinya Kimura, Eizaburo Sueoka, Naoko Aragane
Summary: The study suggests that rs671 may be an accurate and cost-effective predictor of PD-1/PD-L1 inhibitor treatment, in which optimal case selection is an important issue.
Review
Immunology
Xuan Zhao, Yulin Bao, Bi Meng, Zijian Xu, Sijin Li, Xu Wang, Rui Hou, Wen Ma, Dan Liu, Junnian Zheng, Ming Shi
Summary: Developing biomarkers for predicting the efficacy of immune checkpoint inhibitor therapies is important for avoiding side effects and economic burden. Current assays evaluating PD-L1 expression are imperfect, but recent studies are advancing the methodologies to improve accuracy. This includes standardization of immunohistochemistry tests and the use of novel in vivo probes and liquid biopsy. Considering PD-L1 expression on non-tumor cells and utilizing artificial intelligence can further enhance the predictive accuracy of PD-L1 as a biomarker.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Oncology
Zhaodan Xin, Liting You, Feifei Na, Jin Li, Min Chen, Jiajia Song, Ling Bai, Jie Chen, Juan Zhou, Binwu Ying
Summary: In this study, the researchers identified several immunogenetic variants associated with immune-related adverse events (irAEs) and irAEs-free survival in patients treated with PD-1/PD-L1 inhibitors, which could serve as potential predictive biomarkers.
EUROPEAN JOURNAL OF CANCER
(2023)
Review
Medicine, Research & Experimental
Elina Khatoon, Dey Parama, Aviral Kumar, Mohammed S. Alqahtani, Mohamed Abbas, Sosmitha Girisa, Gautam Sethi, Ajaikumar B. Kunnumakkara
Summary: Ovarian cancer is a deadly gynecological cancer with a low survival rate. Recent advancements in immunotherapy, particularly targeting the PD-1/PD-L1 axis, have shown promise in enhancing anti-tumor activity. Combinatorial treatment with small molecule inhibitors has also shown improved efficacy.
Article
Nanoscience & Nanotechnology
Parisa Badiee, Michelle F. Maritz, Nicole Dmochowska, Edward Cheah, Benjamin Thierry
Summary: This study investigates the biodistribution of intratumorally administered aPD-1 nanoformulation and finds that it has lower off-target organ distribution and higher accumulation in tumors and tumor draining lymph nodes compared to free antibodies. In vitro studies also show that aPD-1 nanoformulation effectively inhibits PD-1 expression on T-cells and enhances their cytotoxicity against head and neck cancer cells. Further research is needed to assess the potential of intratumoral administration of aPD-1 nanoformulation in reducing toxicity and improving the tumor efficacy of immune checkpoint inhibitors.
ACS APPLIED MATERIALS & INTERFACES
(2022)
Article
Chemistry, Multidisciplinary
Tatsuya Fukushima, Sayan Gupta, Behzad Rad, Jose A. Cornejo, Christopher J. Petzold, Leanne Jade G. Chan, Rena A. Mizrahi, Code Y. Ralston, Caroline M. Ajo-Franklin
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2017)
Article
Medicine, Research & Experimental
Adam S. Adler, Rena A. Mizrahi, Matthew J. Spindler, Matthew S. Adams, Michael A. Asensio, Robert C. Edgar, Jackson Leong, Renee Leong, Lucy Roalfe, Rebecca White, David Goldblatt, David S. Johnson
Article
Medicine, Research & Experimental
Adam S. Adler, Daniel Bedinger, Matthew S. Adams, Michael A. Asensio, Robert C. Edgar, Renee Leong, Jackson Leong, Rena A. Mizrahi, Matthew J. Spindler, Srinivasa Rao Bandi, Haichun Huang, Pallavi Tawde, Peter Brams, David S. Johnson
Article
Medicine, Research & Experimental
Michael A. Asensio, Yoong Wearn Lim, Nicholas Wayham, Kacy Stadtmiller, Robert C. Edgar, Jackson Leong, Renee Leong, Rena A. Mizrahi, Matthew S. Adams, Jan Fredrik Simons, Matthew J. Spindler, David S. Johnson, Adam S. Adler
Article
Biotechnology & Applied Microbiology
Matthew J. Spindler, Ayla L. Nelson, Ellen K. Wagner, Natasha Oppermans, John S. Bridgeman, James M. Heather, Adam S. Adler, Michael A. Asensio, Robert C. Edgar, Yoong Wearn Lim, Everett H. Meyer, Robert E. Hawkins, Mark Cobbold, David S. Johnson
NATURE BIOTECHNOLOGY
(2020)
Article
Biotechnology & Applied Microbiology
Sheila M. Keating, Rena A. Mizrahi, Matthew S. Adams, Michael A. Asensio, Emily Benzie, Kyle P. Carter, Yao Chiang, Robert C. Edgar, Bishal K. Gautam, Ashley Gras, Jackson Leong, Renee Leong, Yoong Wearn Lim, Vishal A. Manickam, Angelica Medina-Cucurella, Ariel R. Niedecken, Jasmeen Saini, Jan Fredrik Simons, Matthew J. Spindler, Kacy Stadtmiller, Brendan Tinsley, Ellen K. Wagner, Nicholas Wayham, LaRee Tracy, Carina Vingsbo Lundberg, Dirk Buscher, Jose Vicente Terencio, Lucy Roalfe, Emma Pearce, Hayley Richardson, David Goldblatt, Anushka T. Ramjag, Christine V. F. Carrington, Graham Simmons, Marcus O. Muench, Steven M. Chamow, Bryan Monroe, Charles Olson, Thomas H. Oguin, Heather Lynch, Robert Jeanfreau, Rachel A. Mosher, Matthew J. Walch, Christopher R. Bartley, Carl A. Ross, Everett H. Meyer, Adam S. Adler, David S. Johnson
Summary: This method utilizes diverse mammalian antibody repertoires to create recombinant antibody mixtures enriched for specificity and activity against therapeutic targets, allowing for the generation of hyperimmune globulins against various diseases. Additionally, a recombinant human version was developed to address limitations of existing antibody therapeutics, such as rabbit-derived anti-thymocyte globulin.
NATURE BIOTECHNOLOGY
(2021)
Article
Medicine, Research & Experimental
Yoong Wearn Lim, Adam S. Adler, David S. Johnson
Summary: This study utilized deep learning methods to investigate antibody sequences, encoding antibody images and training neural network models for classification, and further generating synthetic antibodies using generative adversarial network models. The results demonstrate that deep learning methods can offer insights into antibody engineering, optimization, and discovery by mining and learning patterns in antibody sequences.
Article
Microbiology
Rena A. Mizrahi, Wendy Y. Lin, Ashley Gras, Ariel R. Niedecken, Ellen K. Wagner, Sheila M. Keating, Nikita Ikon, Vishal A. Manickam, Michael A. Asensio, Jackson Leong, Angelica Medina-Cucurella, Emily Benzie, Kyle P. Carter, Yao Chiang, Robert C. Edgar, Renee Leong, Yoong Wearn Lim, Jan Fredrik Simons, Matthew J. Spindler, Kacy Stadtmiller, Nicholas Wayham, Dirk Buscher, Jose Vicente Terencio, Clara Di Germanio, Steven M. Chamow, Charles Olson, Paula A. Pino, Jun-Gyu Park, Amberlee Hicks, Chengjin Ye, Andreu Garcia-Vilanova, Luis Martinez-Sobrido, Jordi B. Torrelles, David S. Johnson, Adam S. Adler
Summary: This study successfully generated a first-in-class recombinant hyperimmune globulin therapeutic against SARS-CoV-2 using microfluidics, flow sorting, and a targeted integration cell line. The drug was manufactured consistently at the clinical scale and offers a new approach to treating infectious diseases by targeting multiple epitopes of the virus.
Article
Medicine, Research & Experimental
Jan Fredrik Simons, Yoong Wearn Lim, Kyle P. Carter, Ellen K. Wagner, Nicholas Wayham, Adam S. Adler, David S. Johnson
Article
Immunology
Angelica V. Medina-Cucurella, Rena A. Mizrahi, Michael A. Asensio, Robert C. Edgar, Jackson Leong, Renee Leong, Yoong Wearn Lim, Ayla Nelson, Ariel R. Niedecken, Jan Fredrik Simons, Matthew J. Spindler, Kacy Stadtmiller, Nicholas Wayham, Adam S. Adler, David S. Johnson