Medical Specialties Commons^™

The Future Of Targeted Therapy For Leiomyosarcoma, Ryan A Denu, Amanda M Dann, Emily Z Keung, Michael S Nakazawa, Elise F Nassif Haddad

Faculty, Staff and Student Publications

Leiomyosarcoma (LMS) is an aggressive subtype of soft tissue sarcoma that arises from smooth muscle cells, most commonly in the uterus and retroperitoneum. LMS is a heterogeneous disease with diverse clinical and molecular characteristics that have yet to be fully understood. Molecular profiling has uncovered possible targets amenable to treatment, though this has yet to translate into approved targeted therapies in LMS. This review will explore historic and recent findings from molecular profiling, highlight promising avenues of current investigation, and suggest possible future strategies to move toward the goal of molecularly matched treatment of LMS. We focus on targeting the …

Estrogen Receptor Mutations As Novel Targets For Immunotherapy In Metastatic Estrogen Receptor-Positive Breast Cancer, Jonathan Goldberg, Na Qiao, Jennifer L Guerriero, Brett Gross, Yagiz Meneksedag, Yoshimi F Lu, Anne V Philips, Tasnim Rahman, Funda Meric-Bernstam, Jason Roszik, Ken Chen, Rinath Jeselsohn, Sara M Tolaney, George E Peoples, Gheath Alatrash, Elizabeth A Mittendorf

Faculty, Staff and Student Publications

UNLABELLED: Estrogen receptor-positive (ER+) breast cancer is not considered immunogenic and, to date, has been proven resistant to immunotherapy. Endocrine therapy remains the cornerstone of treatment for ER+ breast cancers. However, constitutively activating mutations in the estrogen receptor alpha (ESR1) gene can emerge during treatment, rendering tumors resistant to endocrine therapy. Although these mutations represent a pathway of resistance, they also represent a potential source of neoepitopes that can be targeted by immunotherapy. In this study, we investigated ESR1 mutations as novel targets for breast cancer immunotherapy. Using machine learning algorithms, we identified ESR1-derived peptides predicted to form stable complexes …

Sting Licensing Of Type I Dendritic Cells Potentiates Antitumor Immunity, Jian Wang, Suxin Li, Maggie Wang, Xu Wang, Shuqing Chen, Zhichen Sun, Xiubao Ren, Gang Huang, Baran D Sumer, Nan Yan, Yang-Xin Fu, Jinming Gao

Faculty, Staff and Student Publications

Stimulator of interferon genes (STING) is an immune adaptor protein that senses cyclic GMP-AMP (cGAMP) in response to self or microbial cytosolic DNA as a danger signal. STING is ubiquitously expressed in diverse cell populations including cancer cells with distinct cellular functions such as activation of type I interferons, autophagy induction, or triggering apoptosis. It is not well understood whether and which subsets of immune cells, stromal cells, or cancer cells are particularly important for STING-mediated antitumor immunity. Here using a polymeric STING-activating nanoparticle (PolySTING) with a “shock-and-lock” dual activation mechanism, we show type 1 conventional dendritic cell (cDC1) is …

Three-Year Follow-Up Analysis Of Axicabtagene Ciloleucel In Relapsed/Refractory Indolent Non-Hodgkin Lymphoma (Zuma-5), Sattva S Neelapu, Julio C Chavez, Alison R Sehgal, Narendranath Epperla, Matthew Ulrickson, Emmanuel Bachy, Pashna N Munshi, Carla Casulo, David G Maloney, Sven De Vos, Ran Reshef, Lori A Leslie, Olalekan O Oluwole, Ibrahim Yakoub-Agha, Rashmi Khanal, Joseph Rosenblatt, Ronald Korn, Weixin Peng, Christine Lui, Jacob Wulff, Rhine Shen, Soumya Poddar, A Scott Jung, Harry Miao, Sara Beygi, Caron A Jacobson

Faculty, Staff and Student Publications

Axicabtagene ciloleucel (axi-cel) is an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy approved for relapsed/refractory (R/R) follicular lymphoma (FL). Approval was supported by the phase 2, multicenter, single-arm ZUMA-5 study of axi-cel for patients with R/R indolent non-Hodgkin lymphoma (iNHL; N = 104), including FL and marginal zone lymphoma (MZL). In the primary analysis (median follow-up, 17.5 months), the overall response rate (ORR) was 92% (complete response rate, 74%). Here, we report long-term outcomes from ZUMA-5. Eligible patients with R/R iNHL after ≥2 lines of therapy underwent leukapheresis, followed by lymphodepleting chemotherapy and axi-cel infusion (2 × 106 CAR …

Assessment Of Human Leukocyte Antigen-Based Neoantigen Presentation To Determine Pan-Cancer Response To Immunotherapy, Jiefei Han, Yiting Dong, Xiuli Zhu, Alexandre Reuben, Jianjun Zhang, Jiachen Xu, Hua Bai, Jianchun Duan, Rui Wan, Jie Zhao, Jing Bai, Xuefeng Xia, Xin Yi, Chao Cheng, Jie Wang, Zhijie Wang

Faculty, Staff and Student Publications

Despite the central role of human leukocyte antigen class I (HLA-I) in tumor neoantigen presentation, quantitative determination of presentation capacity remains elusive. Based on a pooled pan-cancer genomic dataset of 885 patients treated with immune checkpoint inhibitors (ICIs), we developed a score integrating the binding affinity of neoantigens to HLA-I, as well as HLA-I allele divergence, termed the HLA tumor-Antigen Presentation Score (HAPS). Patients with a high HAPS were more likely to experience survival benefit following ICI treatment. Analysis of the tumor microenvironment indicated that the antigen presentation pathway was enriched in patients with a high HAPS. Finally, we built …

Rapid Anti-Myeloma Activity By T Cells Expressing An Anti-Bcma Car With A Human Heavy-Chain-Only Antigen-Binding Domain, Lekha Mikkilineni, Danielle A Natrakul, Norris Lam, Elisabet E Manasanch, Jennifer Mann, Katherine A Weissler, Nathan Wong, Jennifer N Brudno, Stephanie L Goff, James C Yang, Micaela Ganaden, Rashmika Patel, Zhili Zheng, Jared J Gartner, Kathryn R Martin, Hao-Wei Wang, Constance M Yuan, Tyler Lowe, Irina Maric, Lipei Shao, Ping Jin, David F Stroncek, Steven L Highfill, Steven A Rosenberg, James N Kochenderfer

Faculty, Staff and Student Publications

Multiple myeloma (MM) is a rarely curable malignancy of plasma cells. MM expresses B cell maturation antigen (BCMA). We developed a fully human anti-BCMA chimeric antigen receptor (CAR) with a heavy-chain-only antigen-recognition domain, a 4-1BB domain, and a CD3ζ domain. The CAR was designated FHVH33-CD8BBZ. We conducted the first-in-humans clinical trial of T cells expressing FHVH33-CD8BBZ (FHVH-T). Twenty-five patients with relapsed MM were treated. The stringent complete response rate (sCR) was 52%. Median progression-free survival (PFS) was 78 weeks. Of 24 evaluable patients, 6 (25%) had a maximum cytokine-release syndrome (CRS) grade of 3; no patients had CRS of greater …

Nivolumab Monotherapy Or Combination With Ipilimumab With Or Without Cobimetinib In Previously Treated Patients With Pancreatic Adenocarcinoma (Checkmate 032), Margaret Callahan, Asim Amin, Frederic J Kaye, Michael A Morse, Matthew H Taylor, Katriina J Peltola, Padmanee Sharma, Eileen M O'Reilly, Stephanie Meadows Shropshire, Shaun O'Brien, Marina Tschaika, Dung T Le

Faculty, Staff and Student Publications

BACKGROUND: Pancreatic cancer is one of the deadliest cancer types and represents a major unmet medical need. CheckMate 032 investigated safety and efficacy of nivolumab monotherapy and nivolumab plus ipilimumab with/without cobimetinib in advanced/metastatic solid tumors, including pancreatic cancer.

METHODS: In the original pancreatic cancer cohort, previously treated patients (≥1 prior regimen) with advanced/metastatic pancreatic adenocarcinoma were assigned to nivolumab 3 mg/kg every 2 weeks (monotherapy arm) or nivolumab 1 mg/kg and ipilimumab 1 mg/kg or 3 mg/kg every 3 weeks for four doses, followed by nivolumab 3 mg/kg every 2 weeks (combination arm). A subsequent modified pancreatic cohort (one …

Efficacy And Safety Of Autologous Tumor-Infiltrating Lymphocytes In Recurrent Or Refractory Ovarian Cancer, Colorectal Cancer, And Pancreatic Ductal Adenocarcinoma, Rodabe Amaria, Anne Knisely, David Vining, Scott Kopetz, Michael J Overman, Milind Javle, Mara B Antonoff, Ching-Wei D Tzeng, Robert A Wolff, Shubham Pant, Kathryn Lito, Kelly Rangel, Bryan Fellman, Ying Yuan, Karen H Lu, Donastas Sakellariou-Thompson, Cara L Haymaker, Marie-Andrée Forget, Patrick Hwu, Chantale Bernatchez, Amir A Jazaeri

Faculty, Staff and Student Publications

BACKGROUND: Tumor-infiltrating lymphocyte (TIL) therapy has shown efficacy in metastatic melanoma, non-small cell lung cancer, and other solid tumors. Our preclinical work demonstrated more robust CD8 predominant TIL production when agonistic anti-4-1BB and CD3 antibodies were used in early ex vivo TIL culture.

METHODS: Patients with treatment-refractory metastatic colorectal (CRC), pancreatic (PDAC) and ovarian (OVCA) cancers were eligible. Lymphodepleting chemotherapy was followed by infusion of ex vivo expanded TIL, manufactured at MD Anderson Cancer Center with IL-2 and agonistic stimulation of CD3 and 4-1BB (urelumab). Patients received up to six doses of high-dose IL-2 after TIL infusion. Primary endpoint was …

Unanswered Questions Following Reports Of Secondary Malignancies After Car-T Cell Therapy, Bruce L Levine, Marcelo C Pasquini, John E Connolly, David L Porter, Michael P Gustafson, Jaap J Boelens, Edwin M Horwitz, Stephan A Grupp, Marcela V Maus, Frederick L Locke, Fabio Ciceri, Annalisa Ruggeri, John Snowden, Helen E Heslop, Crystal L Mackall, Carl H June, Anna M Sureda, Miguel-Angel Perales

Faculty, Staff and Students Publications

Reports of T cell malignancies after CAR-T cell therapy should be investigated, but existing data from follow-up studies suggest a low risk compared with other cancer treatments.

Successful Reuse Of A Donor Heart, Isaac S Alderete, Qimeng Gao, Abigail Benkert, Katherine Sun, Riley Kahan, Kannan Samy, Vincenzo Villani, Joseph W Turek, Deepak Vikraman, Carmelo A Milano, Michael W Manning, Andrew S Barbas

Faculty, Staff and Student Publications

Advances in surgical technique and multidisciplinary management have improved long-term survival for patients born with single ventricle physiology. However, patients who have undergone Fontan completion remain at risk for long-term comorbidities associated with the complex hemodynamic changes following the procedure, including Fontan failure and Fontan-associated liver disease.1 Combined heart-liver transplantation (CHLT) is a rare but lifesaving procedure that has been described in the setting of heart and liver failure secondary to Fontan failure.2 As long-term survival continues to improve for Fontan patients, the incidence of Fontan-associated liver disease will increase. Thus, improving CHLT outcomes and access to both …

Phase 1/2 Trial Of Avelumab Combined With Utomilumab (4–1bb Agonist), Pf-04518600 (Ox40 Agonist), Or Radiotherapy In Patients With Advanced Gynecologic Malignancies, Anne Knisely, Jibran Ahmed, Bettzy Stephen, Sarina A Piha-Paul, Daniel Karp, Abdulrazzak Zarifa, Siqing Fu, David Sanghyun Hong, Jordi Rodon Ahnert, Timothy A Yap, Apostolia M Tsimberidou, Anas Alshawa, Ecaterina E Dumbrava, Yali Yang, Juhee Song, Funda Meric-Bernstam, Amir A Jazaeri, Aung Naing

Faculty, Staff and Student Publications

Background: Immune checkpoint blockade has shown mixed results in advanced/recurrent gynecologic malignancies. Efficacy may be improved through costimulation with OX40 and 4-1BB agonists. The authors sought to evaluate the safety and efficacy of avelumab combined with utomilumab (a 4-1BB agonist), PF-04518600 (an OX40 agonist), and radiotherapy in patients with recurrent gynecologic malignancies.

Methods: The primary end point in this six-arm, phase 1/2 trial was safety of the combination regimens. Secondary end points included the objective response rate (ORR) according to Response Evaluation Criteria in Solid Tumors and immune-related Response Evaluation Criteria in Solid Tumors, the disease control rate (DCR), the …

The Future Of Targeting Cytotoxic T-Lymphocyte-Associated Protein-4: Is There A Role?, Anna Maria Di Giacomo, Michael Lahn, Alexander Mm Eggermont, Bernard Fox, Ramy Ibrahim, Padmanee Sharma, James P Allison, Michele Maio

Faculty, Staff and Student Publications

The 2022 yearly Think Tank Meeting in Siena, Tuscany (Italy), organized by the Italian Network for Tumor Biotherapy (NIBIT) Foundation, the Parker Institute for Cancer Immunotherapy and the World Immunotherapy Council, included a focus on the future of integrating and expanding the use of targeting cytotoxic T-lymphocyte-associated protein 4 (CTLA-4). The conference members exchanged their views on the lessons from targeting CTLA-4 and compared the effect to the impact of blocking Programmed cell death protein 1 (PD1) or its ligand (PDL1). The increasing experience with both therapeutic approaches and their combination suggests that targeting CTLA-4 may lead to more durable …

Locoregional Therapies In Immunologically "Cold" Tumors: Opportunities And Clinical Trial Design Considerations, Pavlos Msaouel, Rahul A Sheth

Faculty, Staff and Student Publications

Immunotherapy has revolutionized cancer management, but many tumors, particularly immunologically "cold" tumors, remain resistant to the therapy. The combination of conventional systemic immunotherapies and locoregional interventional radiology approaches is being explored to transform these cold tumors into immunologically active "hot" ones. The present article uses the example of chromophobe renal cell carcinoma (ChRCC), a renal cell carcinoma subtype resistant to current systemic immunotherapies, to address practical and conceptual challenges that have prevented the activation of clinical trials specifically designed for this malignancy to date. The practical framework discussed herein can help overcome logistic and funding limitations and facilitate the development …

Management Of Infliximab Refractory Immune Checkpoint Inhibitor Gastrointestinal Toxicity: A Multicenter Case Series, Catriona Harvey, Kazi J Nahar, Janet Mckeown, Serigne N Lo, Sheima Farag, Nadia Yousaf, Kate Young, Liselotte Tas, Aafke Meerveld-Eggink, Christian Blank, Austin Thomas, Jennifer Mcquade, Bastian Schilling, Douglas B Johnson, Roberto Martín Huertas, Ana Arance, Joanna Lee, Lisa Zimmer, Georgina V Long, Matteo S Carlino, Yinghong Wang, Alexander Maxwell Menzies

Faculty, Staff and Student Publications

Background: Immune checkpoint inhibitor (ICI) gastrointestinal toxicity (gastritis, enteritis, colitis) is a major cause of morbidity and treatment-related death. Guidelines agree steroid-refractory cases warrant infliximab, however best management of infliximab-refractory ICI gastrointestinal toxicity (IRIGItox) is unknown.

Methods: We conducted an international multicenter retrospective case series. IRIGItox was defined as failure of symptom resolution ≤grade 1 (Common Terminology Criteria for Adverse Events V.5.0) following ≥2 infliximab doses or failure of symptom resolution ≤grade 2 after one dose. Data were extracted regarding demographics, steroid use, response to treatment, and survival outcomes. Toxicity was graded at symptom onset and time of infliximab failure. …

Evaluation Of Potential Biomarkers For Lenvatinib Plus Pembrolizumab Among Patients With Advanced Endometrial Cancer: Results From Study 111/Keynote-146, Vicky Makker, Matthew H Taylor, Carol Aghajanian, Allen L Cohn, Marcia S Brose, Christopher Di Simone, Zhu Alexander Cao, Leah Suttner, Andrey Loboda, Razvan Cristescu, Petar Jelinic, Robert Orlowski, Lea Dutta, Junji Matsui, Corina E Dutcus, Yukinori Minoshima, Mark J Messing

Faculty, Staff and Student Publications

BACKGROUND: Lenvatinib plus pembrolizumab demonstrated clinically meaningful benefit in patients with previously treated advanced endometrial carcinoma in Study 111/KEYNOTE-146 (NCT02501096). In these exploratory analyses from this study, we evaluated the associations between clinical outcomes and gene expression signature scores and descriptively summarized response in biomarker subpopulations defined by tumor mutational burden (TMB) and DNA variants for individual genes of interest.

METHODS: Patients with histologically confirmed metastatic endometrial carcinoma received oral lenvatinib 20 mg once daily plus intravenous pembrolizumab 200 mg every 3 weeks for 35 cycles. Archived formalin-fixed paraffin-embedded tissue was obtained from all patients. T-cell-inflamed gene expression profile (Tcell …

Targeting Innate Immunity In Glioma Therapy, Andrew G Gillard, Dong Ho Shin, Lethan A Hampton, Andres Lopez-Rivas, Akhila Parthasarathy, Juan Fueyo, Candelaria Gomez-Manzano

Faculty, Staff and Student Publications

Currently, there is a lack of effective therapies for the majority of glioblastomas (GBMs), the most common and malignant primary brain tumor. While immunotherapies have shown promise in treating various types of cancers, they have had limited success in improving the overall survival of GBM patients. Therefore, advancing GBM treatment requires a deeper understanding of the molecular and cellular mechanisms that cause resistance to immunotherapy. Further insights into the innate immune response are crucial for developing more potent treatments for brain tumors. Our review provides a brief overview of innate immunity. In addition, we provide a discussion of current therapies …

Vaccines: A Promising Therapy For Myelodysplastic Syndrome, Kriti Gera, Anjali Chauhan, Paul Castillo, Maryam Rahman, Akash Mathavan, Akshay Mathavan, Elizabeth Oganda-Rivas, Leighton Elliott, John R Wingard, Elias J Sayour

Faculty, Staff and Student Publications

Myelodysplastic neoplasms (MDS) define clonal hematopoietic malignancies characterized by heterogeneous mutational and clinical spectra typically seen in the elderly. Curative treatment entails allogeneic hematopoietic stem cell transplant, which is often not a feasible option due to older age and significant comorbidities. Immunotherapy has the cytotoxic capacity to elicit tumor-specific killing with long-term immunological memory. While a number of platforms have emerged, therapeutic vaccination presents as an appealing strategy for MDS given its promising safety profile and amenability for commercialization. Several preclinical and clinical trials have investigated the efficacy of vaccines in MDS; these include peptide vaccines targeting tumor antigens, whole …

Product Attributes Of Car T-Cell Therapy Differentially Associate With Efficacy And Toxicity In Second-Line Large B-Cell Lymphoma (Zuma-7), Simone Filosto, Saran Vardhanabhuti, Miguel A Canales, Xavier Poiré, Lazaros J Lekakis, Sven De Vos, Craig A Portell, Zixing Wang, Christina To, Marco Schupp, Soumya Poddar, Tan Trinh, Carmen M Warren, Ethan G Aguilar, Justin Budka, Paul Cheng, Justin Chou, Adrian Bot, Rhine R Shen, Jason R Westin

Faculty, Staff and Student Publications

Treatment resistance and toxicities remain a risk following chimeric antigen receptor (CAR) T-cell therapy. Herein, we report pharmacokinetics, pharmacodynamics, and product and apheresis attributes associated with outcomes among patients with relapsed/refractory large B-cell lymphoma (LBCL) treated with axicabtagene ciloleucel (axi-cel) in ZUMA-7. Axi-cel peak expansion associated with clinical response and toxicity, but not response durability. In apheresis material and final product, a naive T-cell phenotype (CCR7+CD45RA+) expressing CD27 and CD28 associated with improved response durability, event-free survival, progression-free survival, and a lower number of prior therapies. This phenotype was not associated with high-grade cytokine release syndrome (CRS) or neurologic events. …

Class Ii Hla-Drb4 Is A Predictive Biomarker For Survival Following Immunotherapy In Metastatic Non-Small Cell Lung Cancer, Cindy Y Jiang, Lili Zhao, Michael D Green, Shashidhar Ravishankar, Andrea M H Towlerton, Anthony J Scott, Malini Raghavan, Matthew F Cusick, Edus H Warren, Nithya Ramnath

Faculty, Staff and Student Publications

Immune checkpoint inhibitors (ICI) are important treatment options for metastatic non-small cell lung cancer (mNSCLC). However, not all patients benefit from ICIs and can experience immune-related adverse events (irAEs). Limited understanding exists for germline determinants of ICI efficacy and toxicity, but Human Leukocyte Antigen (HLA) genes have emerged as a potential predictive biomarker. We performed HLA typing on 85 patients with mNSCLC, on ICI therapy and analyzed the impact of HLA Class II genotype on progression free survival (PFS), overall survival (OS), and irAEs. Most patients received pembrolizumab (83.5%). HLA-DRB4 genotype was seen in 34/85 (40%) and its presence correlated …

Cancer Research Provides A Model For Advancing Clinical Trials In Dementia In The Era Of Disease-Modifying Alzheimer’S-Type Dementia Therapies, Gregory Jicha, Thomas Tucker, Susanne Arnold, Peter T. Nelson

Neurology Faculty Publications

Dementia and cancer are multifactorial, widely-feared, age-associated clinical syndromes that are increasing in prevalence. There have been major breakthroughs in clinical cancer research leading to some effective treatments, whereas the field of dementia has achieved comparatively limited success in clinical research. The lessons of cancer research may help those in the dementia research field in confronting some of the dilemmas faced when the clinical care regimen is not entirely safe or efficacious. Cancer clinical trials have assumed that untreated individuals with cancer are at high risk for morbidity and mortality after primary diagnoses. Thus, patients deserve a choice of clinical …

Determining Effective Treatment Regimens For Breast Cancer Using Combined Immunotherapy And Chemotherapy In Vivo, Akhila Kunuthuru

AUCTUS: The Journal of Undergraduate Research and Creative Scholarship

Breast cancer has the highest incidence rate of all cancers globally in women, and those of African descent, especially West African females, face higher rates of triple-negative breast cancer (TNBC), a more aggressive form of breast cancer. Immunotherapy for breast cancer is a relatively new treatment option, and research is ongoing to identify the best combination treatments for increasing survival of those diagnosed with TNBC. Eganelisib (IPI-549: a PI3K-gamma inhibitor that works to shift M2 macrophages to M1 to augment T cell function) with other combinatory treatments has shown promising results in reducing tumor growth and increasing survival in mice. …

Food Allergies, The Immune Response, And Preventative Treatments: Milk, Egg, And Shellfish Allergies, Marissa Dimatteo

Undergraduate Honors Theses

Food allergies have been an increasing concern worldwide with very little information on preventative measures and treatment. They can have long lasting and life-threatening consequences with a wide range of symptoms from hives to anaphylactic shock. Long recommended feeding guidelines, vitamin and mineral deficiencies, and gastrointestinal alterations are thought to play a role in the increase in food allergies in infants. Early introduction of food, immunotherapy, and a properly supported gut microbiome have been recommended to decrease the likelihood of developing a food allergy and desensitizing the immune system.

Repolarizing Tumor-Associated Macrophages In Ovarian Cancer: A Novel Immunotherapeutic Approach, David Schweer

Theses and Dissertations--Clinical and Translational Science

Ovarian cancer, recognized for its high lethality and resistance to conventional immunotherapies, mandates innovative strategies to confront its intricate challenges. The tumor microenvironment (TME), orchestrated by tumor-associated macrophages (TAMs), assumes a pivotal role in disease progression, rendering TAMs an appealing therapeutic target. This study endeavors to explore the prospect of repolarizing TAMs from a protumor M2 phenotype to an antitumor M1 state, employing M1 macrophage-derived vesicles (MEVs) as a groundbreaking immunotherapeutic approach.

The primary objective is to investigate the capacity of M1 MEVs to repolarize M2 macrophages in vitro towards an anti-tumor M1-like phenotype. By inducing human macrophages to adopt …

Toxicity In The Era Of Immune Checkpoint Inhibitor Therapy, Synat Keam, Naimah Turner, Fernanda G Kugeratski, Rene Rico, Jocelynn Colunga-Minutti, Rayansh Poojary, Sayan Alekseev, Anisha B Patel, Yuanteng Jeff Li, Ajay Sheshadri, Monica E Loghin, Karin Woodman, Ashley E Aaroe, Sarah Hamidi, Priyanka Chandrasekhar Iyer, Nicolas L Palaskas, Yinghong Wang, Roza Nurieva

Faculty, Staff and Student Publications

Immune checkpoint inhibitors (ICIs) reinvigorate anti-tumor immune responses by disrupting co-inhibitory immune checkpoint molecules such as programmed cell death 1 (PD-1) and cytotoxic T lymphocyte antigen 4 (CTLA-4). Although ICIs have had unprecedented success and have become the standard of care for many cancers, they are often accompanied by off-target inflammation that can occur in any organ system. These immune related adverse events (irAEs) often require steroid use and/or cessation of ICI therapy, which can both lead to cancer progression. Although irAEs are common, the detailed molecular and immune mechanisms underlying their development are still elusive. To further our understanding …

Fam20a: A Potential Diagnostic Biomarker For Lung Squamous Cell Carcinoma, Yalin Zhang, Qin Sun, Yangbo Liang, Xian Yang, Hailian Wang, Siyuan Song, Yi Wang, Yong Feng

Faculty, Staff and Students Publications

Background: Lung squamous cell carcinoma (LUSC) ranks among the carcinomas with the highest incidence and dismal survival rates, suffering from a lack of effective therapeutic strategies. Consequently, biomarkers facilitating early diagnosis of LUSC could significantly enhance patient survival. This study aims to identify novel biomarkers for LUSC.

Methods: Utilizing the TCGA, GTEx, and CGGA databases, we focused on the gene encoding Family with Sequence Similarity 20, Member A (FAM20A) across various cancers. We then corroborated these bioinformatic predictions with clinical samples. A range of analytical tools, including Kaplan-Meier, MethSurv database, Wilcoxon rank-sum, Kruskal-Wallis tests, Gene Set Enrichment Analysis, …

Advancing Kidney Xenotransplantation With Anesthesia And Surgery – Bridging Preclinical And Clinical Frontiers Challenges And Prospects, Xiaojian Zhang, Hailian Wang, Qin Xie, Yang Zhang, Yixin Yang, Man Yuan, Yuqi Cui, Si-Yuan Song, Jianzhen Lv, Yi Wang

Children’s Nutrition Research Center Staff Publications

Xenotransplantation is emerging as a vital solution to the critical shortage of organs available for transplantation, significantly propelled by advancements in genetic engineering and the development of sophisticated immunosuppressive treatments. Specifically, the transplantation of kidneys from genetically engineered pigs into human patients has made significant progress, offering a potential clinical solution to the shortage of human kidney supply. Recent trials involving the transplantation of these modified porcine kidneys into deceased human bodies have underscored the practicality of this approach, advancing the field towards potential clinical applications. However, numerous challenges remain, especially in the domains of identifying suitable donor-recipient matches and …

Antiangiogenic Therapy Combined With Immune Checkpoint Blockade In Urothelial Cancer: Systematic Review And Meta-Analysis, Mohammad Jad Moussa, Iuliia Kovalenko, Emanuele Crupi, Ekaterina Proskuriakova, Yimin Geng, Giuseppe Fallara, Raed Benkhadra, Daniele Raggi, Matthew T. Campbell, Pavlos Msaouel, Omar Alhalabi

Department of Medicine Faculty Publications

Background: Antiangiogenic therapy had been tested in urothelial cancer (UC) without reaching the clinic.

Objective: We provide a systematic review and meta-analysis of trials to assess efficacy of immune checkpoint inhibitors (ICI) combined with antiangiogenic agents in UC.

Methods: Following PRISMA guidelines, we searched for trials with at least one arm of patients with UC treated with ICI plus antiangiogenics. Data were analyzed with the "meta" package from R using a one-staged frequentist meta-analysis.

Results: After screening 13,708 titles and abstracts, 9 studies were selected for analysis with 14 identified cohorts comprising 621 patients: 448 were ICI-naïve (ICI-N) and 173 …

Updates Of The Role Of B-Cells In Ischemic Stroke, Silin Wu, Sidra Tabassum, Cole T Payne, Heng Hu, Aaron M Gusdon, Huimahn A Choi, Xuefang S Ren

Faculty, Staff and Student Publications

Ischemic stroke is a major disease causing death and disability in the elderly and is one of the major diseases that seriously threaten human health and cause a great economic burden. In the early stage of ischemic stroke, neuronal structure is destroyed, resulting in death or damage, and the release of a variety of damage-associated pattern molecules induces an increase in neuroglial activation, peripheral immune response, and secretion of inflammatory mediators, which further exacerbates the damage to the blood-brain barrier, exacerbates cerebral edema, and microcirculatory impairment, triggering secondary brain injuries. After the acute phase of stroke, various immune cells initiate …

Real-World Analysis Of Safety And Efficacy Of Car T-Cell Therapy In Lymphoma Patients With Decreased Kidney Function, Omar Mamlouk, Paolo Strati, Lei Feng, Ryan Sun, Amy Ayers, Raphael E Steiner, Ranjit Nair, Christopher Flowers, Jeremy L Ramdial, Neeraj Saini, Samer A Srour, Richard E Champlin, Partow Kebriaei, Loretta J Nastoupil, Maria A Rodriguez, Elizabeth J Shpall, Yago Nieto, Jason Westin, Sattva S Neelapu, Sreedhar Mandayam, Sairah Ahmed

Faculty, Staff and Student Publications

No abstract provided.

Highly Variable Timing Renders Immunotherapy Efficacy And Toxicity Impractical Biomarkers Of One Another In Clinical Practice, Mitchell S Von Itzstein, Yuqiu Yang, Yiqing Wang, David Hsiehchen, Thomas Y Sheffield, Farjana Fattah, Vinita Popat, Murtaza Ahmed, Jade Homsi, Jonathan E Dowell, Sawsan Rashdan, Jay Lohrey, Hans J Hammers, Randall S Hughes, Tao Wang, Yang Xie, David E Gerber

Faculty, Staff and Student Publications

Background: A useful clinical biomarker requires not only association but also a consistent temporal relationship. For instance, chemotherapy-induced neutropenia and epidermal growth-factor inhibitor-related acneiform rash both occur within weeks of treatment initiation, thereby providing information prior to efficacy assessment. Although immune checkpoint inhibitor (ICI)-associated immune-related adverse events (irAE) have been associated with therapeutic benefit, irAE may have delayed and highly variable onset. To determine whether ICI efficacy and irAE could serve as clinically useful biomarkers for predicting each other, we determined the temporal relationship between initial efficacy assessment and irAE onset in a diverse population treated with ICI.

Methods: Using …