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1. RNA aggregates harness the danger response for potent cancer immunotherapy

Author

Mendez-Gomez, Hector R., DeVries, Anna, Castillo, Paul, von Roemeling, Christina, Qdaisat, Sadeem, Stover, Brian D., Xie, Chao, Weidert, Frances, Zhao, Chong, Moor, Rachel, Liu, Ruixuan, Soni, Dhruvkumar, Ogando-Rivas, Elizabeth, Chardon-Robles, Jonathan, McGuiness, James, Zhang, Dingpeng, Chung, Michael C., Marconi, Christiano, Michel, Stephen, Barpujari, Arnav, Jobin, Gabriel W., Thomas, Nagheme, Ma, Xiaojie, Campaneria, Yodarlynis, Grippin, Adam, Karachi, Aida, Li, Derek, Sahay, Bikash, Elliott, Leighton, Foster, Timothy P., Coleman, Kirsten E., Milner, Rowan J., Sawyer, W. Gregory, Ligon, John A., Simon, Eugenio, Cleaver, Brian, Wynne, Kristine, Hodik, Marcia, Molinaro, Annette M., Guan, Juan, Kellish, Patrick, Doty, Andria, Lee, Ji-Hyun, Massini, Tara, Kresak, Jesse L., Huang, Jianping, Hwang, Eugene I., Kline, Cassie, Carrera-Justiz, Sheila, Rahman, Maryam, Gatica, Sebastian, Mueller, Sabine, Prados, Michael, Ghiaseddin, Ashley P., Silver, Natalie L., Mitchell, Duane A., and Sayour, Elias J.

Published
2024
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2. ATP-Binding Cassette Transporter of Clinical Significance: Sideroblastic Anemia.

Author

Ogunbileje, John O., Harris, Neil, Wynn, Tung, Kashif, Reema, Stover, Brian, and Osa-Andrews, Bremansu

Subjects
ATP-binding cassette transporters, ANEMIA, MEMBRANE proteins, GENETIC mutation, CHLORIDE ions
Abstract

The ATP-binding cassette (ABC) transporters are a vast group of 48 membrane proteins, some of which are of notable physiological and clinical importance. Some ABC transporters are involved in functions such as the transport of chloride ions, bilirubin, reproductive hormones, cholesterol, and iron. Consequently, genetic or physiological disruption in these functions is manifested in various disease processes like cystic fibrosis, Tangier disease, and sideroblastic anemia. Among other etiologies, primary sideroblastic anemia results from a genetic mutation in the ATP-binding cassette-7 (ABCB7), a member of the ABC transporter family. There are not many articles specifically tackling the disease processes caused by ABC transporters in detail. Some testing methodologies previously reported in the available literature for investigating sideroblastic anemia need updating. Here, we expound on the relevance of ABCB7 as a clinically important ABC transporter and a rare participant in the disease process of Sideroblastic anemia. The other genetic and secondary etiologies of sideroblastic anemia, which do not involve mutations in the ABCB7 protein, are also described. We review the pathophysiology, clinical course, symptoms, diagnosis, and treatment of sideroblastic anemia with a focus on modern technologies for laboratory testing. [ABSTRACT FROM AUTHOR]

Published
2024
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3. mRNA aggregates harness danger response for potent cancer immunotherapy

Author

Mendez-Gomez, Hector, primary, DeVries, Anna, additional, Castillo, Paul, additional, Stover, Brian, additional, Qdaisat, Sadeem, additional, Von Roemling, Christina, additional, Ogando-Rivas, Elizabeth, additional, Weidert, Frances, additional, McGuiness, James, additional, Zhang, Dingpeng, additional, Chung, Michael C, additional, Li, Derek, additional, Zhao, Chong, additional, Marconi, Christiano, additional, Campaneria, Yodarlynis, additional, Chardon-Robles, Jonathan, additional, Grippin, Adam, additional, Karachi, Aida, additional, Thomas, Nagheme, additional, Huang, Jianping, additional, Milner, Rowan, additional, Sahay, Bikash, additional, Sawyer, Wallace Gregory, additional, Ligon, John A, additional, Silver, Natalie, additional, Simon, Eugenio, additional, Cleaver, Brian, additional, Wynne, Kristine, additional, Hodik, Marcia, additional, Molinaro, Annette, additional, Guan, Juan, additional, Kellish, Patrick, additional, Doty, Andria, additional, Lee, Ji-Hyun, additional, Carrera-Justiz, Sheila, additional, Rahman, Maryam, additional, Gatica, Sebastian, additional, Mueller, Sabine, additional, Prados, Michael, additional, Ghiaseddin, Ashley, additional, Mitchell, Duane A, additional, and Sayour, Elias J, additional

Published
2023
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4. mRNA aggregates harness danger response for potent cancer immunotherapy

Author

Mendez-Gomez, Hector R., DeVries, Anna, Castillo, Paul, Stover, Brian D., Qdaisat, Sadeem, Von Roemeling, Christina, Ogando-Rivas, Elizabeth, Weidert, Frances, McGuiness, James, Zhang, Dingpeng, Chung, Michael C., Li, Derek, Zhang, Chong, Marconi, Christiano, Campaneria, Yodarlynis, Chardon-Robles, Jonathan, Grippin, Adam, Karachi, Aida, Thomas, Nagheme, Huang, Jianping, Milner, Rowan, Sahay, Bikash, Sawyer, W. Gregory, Ligon, John A., Silver, Natalie, Simon, Eugenio, Cleaver, Brian, Wynne, Kristine, Hodik, Marcia, Molinaro, Anette, Guan, Juan, Kellish, Patrick, Doty, Andria, Lee, Ji-Hyun, Carrera-Justiz, Sheila, Rahman, Maryam, Gatica, Sebastian, Mueller, Sabine, Prados, Michael, Ghiaseddin, Ashley, Mitchell, Duane A., and Sayour, Elias J.

Subjects
Article
Abstract

Messenger RNA (mRNA) has emerged as a remarkable tool for COVID-19 prevention but its use for induction of therapeutic cancer immunotherapy remains limited by poor antigenicity and a regulatory tumor microenvironment (TME). Herein, we develop a facile approach for substantially enhancing immunogenicity of tumor-derived mRNA in lipid-particle (LP) delivery systems. By using mRNA as a molecular bridge with ultrapure liposomes and foregoing helper lipids, we promote the formation of ‘onion-like’ multi-lamellar RNA-LP aggregates (LPA). Intravenous administration of RNA-LPAs mimics infectious emboli and elicits massive DC/T cell mobilization into lymphoid tissues provoking cancer immunogenicity and mediating rejection of both early and late-stage murine tumor models. Unlike current mRNA vaccine designs that rely on payload packaging into nanoparticle cores for toll-like receptor engagement, RNA-LPAs stimulate intracellular pathogen recognition receptors (RIG-I) and reprogram the TME thus enabling therapeutic T cell activity. RNA-LPAs were safe in acute/chronic murine GLP toxicology studies and immunologically active in client-owned canines with terminal gliomas. In an early phase first-in-human trial for patients with glioblastoma, we show that RNA-LPAs encoding for tumor-associated antigens elicit rapid induction of pro-inflammatory cytokines, mobilization/activation of monocytes and lymphocytes, and expansion of antigen-specific T cell immunity. These data support the use of RNA-LPAs as novel tools to elicit and sustain immune responses against poorly immunogenic tumors.

Published
2023

6. 1390 RNA nanoparticle vaccines overcome the immunosuppressive tumor microenvironment of metastatic osteosarcoma

Author

Ligon, John, primary, Stover, Brian, additional, Mendez-Gomez, Hector, additional, Grippin, Adam, additional, Weidert, Frances, additional, Fagman, Lana, additional, Chardon-Robles, Jonathan, additional, Castillo, Paul, additional, Silver, Natalie, additional, Lagmay, Joanne, additional, Milner, Rowan, additional, Mitchell, Duane, additional, and Sayour, Elias, additional

Published
2022
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7. CTIM-28. MULTILAMELLAR MRNA LIPID PARTICLES INDUCE IMMUNOLOGIC REPROGRAMMING IN CANINE AND HUMAN GLIOBLASTOMA PATIENTS

Author

Mendez-Gomez, Hector, primary, DeVries, Anna, additional, Stover, Brian, additional, Zhang, Dingpeng, additional, Grippin, Adam, additional, Von Roemeling, Christina, additional, Weidert, Frances, additional, Karachi, Aida, additional, Qdaisat, Sadeem, additional, Thomas, Nagheme, additional, McGuiness, James, additional, Castillo, Paul, additional, Huang, Jianping, additional, Ligon, John, additional, Silver, Natalie, additional, Kellish, Patrick, additional, Doty, Andria, additional, Carrera-Justiz, Sheila, additional, Prados, Michael, additional, Mueller, Sabine, additional, Rahman, Maryam, additional, Ghiaseddin, Ashley, additional, Mitchell, Duane, additional, and Sayour, Elias, additional

Published
2022
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8. Florida Pediatric Bone Marrow Transplant and Cell Therapy Consortium (FPBCC): Tandem Transplant for Neuroblastoma Did Not Improve Overall Survival in Children Transplanted in Florida between 2010 and 2019

Author

Stover, Brian, primary, Chellapandian, Deepak, additional, Ziga, Edward, additional, Silva, Jorge Galvez, additional, Joyce, Michael, additional, Castillo, Paul, additional, Sunkersett, Gauri, additional, Alperstein, Warren, additional, Cline, Jessica, additional, Yang, Fan, additional, Zhao, Jing, additional, Horn, Biljana, additional, and Katzenstein, Howard, additional

Published
2021
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9. Outcomes of Bone Marrow Failure Syndromes Post-Allogeneic HCT Using Enhanced Data Back to Center (eDBtC) Platform: Experience from the Florida Pediatric Bone Marrow Transplant and Cell Therapy Consortium (FPBCC)

Author

Dalal, Mansi, primary, Castillo, Paul, additional, Fort, John, additional, Galvez-Silva, Jorge, additional, Jones, Noah, additional, Garcia, Maylin, additional, Alperstein, Warren, additional, Chellapandian, Deepak, additional, Cline, Jessica, additional, Joyce, Michael, additional, Katzenstein, Howard, additional, Oshrine, Benjamin, additional, Sunkersett, Gauri, additional, Stover, Brian, additional, Walter, Jolan, additional, Yang, Fan, additional, Zhao, Jing, additional, Ziga, Edward, additional, and Horn, Biljana, additional

Published
2021
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10. Outcomes of T- and B-Cell Acute Lymphoblastic Leukemias Post-Allogeneic Transplant (alloHCT) Using Enhanced Data Back to Center (eDBtC) Platform: Experience from the Florida Pediatric Bone Marrow Transplant and Cell Therapy Consortium (FPBCC)

Author

Castillo, Paul, primary, Dalal, Mansi, additional, Fort, John, additional, Jones, Noah, additional, Alperstein, Warren, additional, Chellapandian, Deepak, additional, Cline, Jessica, additional, Galvez-Silva, Jorge, additional, Joyce, Michael, additional, Katzenstein, Howard, additional, Oshrine, Benjamin, additional, Sunkersett, Gauri, additional, Stover, Brian, additional, Walter, Jolan, additional, Yang, Fan, additional, Zhao, Jing, additional, Ziga, Edward, additional, and Horn, Biljana, additional

Published
2021
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13. TMIC-29. METABOLIC INTERACTIONS BETWEEN TREATMENT-RESISTANT SLOW-CYCLING CELLS AND THE IMMUNE SYSTEM IN HIGH-GRADE GLIOMA

Author

Sayour, Elias, primary, Yang, Changlin, additional, Tian, Guimei, additional, Grippin, Adam, additional, Dajac, Mariana, additional, Nazareth, Brian, additional, Andrews, Michael, additional, Karachi, Aida, additional, Mendez-Gomez, Hector, additional, Stover, Brian, additional, Moore, Ginger, additional, Flores-Toro, Joseph, additional, Divita, Bayli, additional, Kresak, Jesse, additional, Rahman, Maryam, additional, Flores, Catherine, additional, Huang, Jianping, additional, Harrison, Jeffrey, additional, Mitchell, Duane, additional, and Deleyrolle, Loic, additional

Published
2019
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16. 521 - Outcomes of Bone Marrow Failure Syndromes Post-Allogeneic HCT Using Enhanced Data Back to Center (eDBtC) Platform: Experience from the Florida Pediatric Bone Marrow Transplant and Cell Therapy Consortium (FPBCC)

Author

Dalal, Mansi, Castillo, Paul, Fort, John, Galvez-Silva, Jorge, Jones, Noah, Garcia, Maylin, Alperstein, Warren, Chellapandian, Deepak, Cline, Jessica, Joyce, Michael, Katzenstein, Howard, Oshrine, Benjamin, Sunkersett, Gauri, Stover, Brian, Walter, Jolan, Yang, Fan, Zhao, Jing, Ziga, Edward, and Horn, Biljana

Published
2021
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18. 144 - Outcomes of T- and B-Cell Acute Lymphoblastic Leukemias Post-Allogeneic Transplant (alloHCT) Using Enhanced Data Back to Center (eDBtC) Platform: Experience from the Florida Pediatric Bone Marrow Transplant and Cell Therapy Consortium (FPBCC)

Author

Castillo, Paul, Dalal, Mansi, Fort, John, Jones, Noah, Alperstein, Warren, Chellapandian, Deepak, Cline, Jessica, Galvez-Silva, Jorge, Joyce, Michael, Katzenstein, Howard, Oshrine, Benjamin, Sunkersett, Gauri, Stover, Brian, Walter, Jolan, Yang, Fan, Zhao, Jing, Ziga, Edward, and Horn, Biljana

Published
2021
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19. STEM-09. CANCER STEM CELL IMMUNOEDITING

Author

Sayour, Elias, primary, Yang, Changlin, additional, Grippin, Adam, additional, Mendez-Gomez, Hector, additional, Dajac, Mariana, additional, Nazareth, Brian, additional, Andrews, Michael, additional, Loche, Tyler, additional, Karachi, Aida, additional, Stover, Brian, additional, Moore, Ginger, additional, Kresak, Jesse, additional, Huang, Jianping, additional, Mitchell, Duane, additional, and Deleyrolle, Loic, additional

Published
2018
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21. Personalized Tumor RNA Loaded Lipid-Nanoparticles Prime the Systemic and Intratumoral Milieu for Response to Cancer Immunotherapy

Author

Sayour, Elias J., primary, Grippin, Adam, additional, De Leon, Gabriel, additional, Stover, Brian, additional, Rahman, Maryam, additional, Karachi, Aida, additional, Wummer, Brandon, additional, Moore, Ginger, additional, Castillo-Caro, Paul, additional, Fredenburg, Kristianna, additional, Sarkisian, Matthew R., additional, Huang, Jianping, additional, Deleyrolle, Loic P., additional, Sahay, Bikash, additional, Carrera-Justiz, Sheila, additional, Mendez-Gomez, Hector R., additional, and Mitchell, Duane A., additional

Published
2018
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24. A Prospective Study of Negative Pressure Wound Therapy With Integrated Irrigation for the Treatment of Diabetic Foot Ulcers

Author

Zelen, Charles M., Stover, Brian, Nielson, David, and Cunningham, Muriel

Subjects
integumentary system, Journal Article
Abstract

Objective: Patients with diabetes often present with pedal wounds resistant to standard wound healing modalities and become chronic in nature. These chronic wounds in diabetic patients have a high incidence of complications including infection and amputation. Negative pressure wound therapy has been found to facilitate healing of the stagnant pedal wound. This protocol was designed to determine wound closure rates using a unique negative pressure wound therapy system that delivers vacuum-assisted wound closure with a simultaneous irrigation feature (Svedman Wound Treatment System). Methods: A prospective single center study was conducted in adults with diabetic foot ulcers ≥cm2 or more in size showing no signs of clinical infection, and having adequate blood flow. Patients received dressing changes and irrigation on a standard regimen with weekly wound assessments for a minimum of 6 weeks. Results: 11 women and 8 men with a mean wound size of 2.4 cm × 2.2 cm were treated with the device. A total of 14 of /19 (74%) patients healed completely, with a median healing time of 34 days (range, 9-114). Eleven of 19 patients (58%) healed within the 6-week evaluation period. For the 5 patients who did not heal completely with the device, other treatments were utilized, including further wound debridement, muscle flaps, and skin grafting procedures. Conclusions: Negative pressure wound therapy with integrated irrigation was well tolerated by the patients without complications related to the device application or irrigation feature. The data clearly suggests that this technology may be a promising alternative for the chronic nonhealing diabetic wound.

Published
2011

28. mRNA aggregates harness danger response for potent cancer immunotherapy.

Author

Mendez-Gomez HR, DeVries A, Castillo P, Stover BD, Qdaisat S, Von Roemeling C, Ogando-Rivas E, Weidert F, McGuiness J, Zhang D, Chung MC, Li D, Zhang C, Marconi C, Campaneria Y, Chardon-Robles J, Grippin A, Karachi A, Thomas N, Huang J, Milner R, Sahay B, Sawyer WG, Ligon JA, Silver N, Simon E, Cleaver B, Wynne K, Hodik M, Molinaro A, Guan J, Kellish P, Doty A, Lee JH, Carrera-Justiz S, Rahman M, Gatica S, Mueller S, Prados M, Ghiaseddin A, Mitchell DA, and Sayour EJ

Abstract

Messenger RNA (mRNA) has emerged as a remarkable tool for COVID-19 prevention but its use for induction of therapeutic cancer immunotherapy remains limited by poor antigenicity and a regulatory tumor microenvironment (TME). Herein, we develop a facile approach for substantially enhancing immunogenicity of tumor-derived mRNA in lipid-particle (LP) delivery systems. By using mRNA as a molecular bridge with ultrapure liposomes and foregoing helper lipids, we promote the formation of 'onion-like' multi-lamellar RNA-LP aggregates (LPA). Intravenous administration of RNA-LPAs mimics infectious emboli and elicits massive DC/T cell mobilization into lymphoid tissues provoking cancer immunogenicity and mediating rejection of both early and late-stage murine tumor models. Unlike current mRNA vaccine designs that rely on payload packaging into nanoparticle cores for toll-like receptor engagement, RNA-LPAs stimulate intracellular pathogen recognition receptors (RIG-I) and reprogram the TME thus enabling therapeutic T cell activity. RNA-LPAs were safe in acute/chronic murine GLP toxicology studies and immunologically active in client-owned canines with terminal gliomas. In an early phase first-in-human trial for patients with glioblastoma, we show that RNA-LPAs encoding for tumor-associated antigens elicit rapid induction of pro-inflammatory cytokines, mobilization/activation of monocytes and lymphocytes, and expansion of antigen-specific T cell immunity. These data support the use of RNA-LPAs as novel tools to elicit and sustain immune responses against poorly immunogenic tumors.

Published
2023
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29. GD2 chimeric antigen receptor modified T cells in synergy with sub-toxic level of doxorubicin targeting osteosarcomas.

Author

Chulanetra M, Morchang A, Sayour E, Eldjerou L, Milner R, Lagmay J, Cascio M, Stover B, Slayton W, Chaicumpa W, Yenchitsomanus PT, and Chang LJ

Abstract

Since the prognosis for children with high-risk osteosarcoma (OS) remains suboptimal despite intensive multi-modality therapies, there is a clear and urgent need for the development of targeted therapeutics against these refractory malignancies. Chimeric antigen receptor (CAR) modified T cells can meet this need by utilizing the immune system's potent cytotoxic mechanisms against tumor specific antigen targets with exquisite specificity. Since OS highly expresses the GD2 antigen, a viable immunotherapeutic target, we sought to assess if CAR modified T cells targeting GD2 could induce cytotoxicity against OS tumor cells. We demonstrated that the GD2 CAR modified T cells were highly efficacious for inducing OS tumor cell death. Interestingly, the OS cells were induced to up-regulate expression of PD-L1 upon interaction with GD2 CAR modified T cells, and the specific interaction induced CAR T cells to overexpress the exhaustion marker PD-1 along with increased CAR T cell apoptosis. To further potentiate CAR T cell killing activity against OS, we demonstrated that suboptimal chemotherapeutic treatment with doxorubicin can synergize with CAR T cells to effectively kill OS tumor cells., Competing Interests: LJC serves as President of Shenzhen Geno-Immune Institute and may benefit financially as a result of the outcomes of LJC’s research or work reported in this publication. The authors declare no competing financial interests., (AJCR Copyright © 2020.)

Published
2020

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