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1,045 results on '"Hwang, Wei-Ting"'

1. Cytokine-mediated CAR T therapy resistance in AML

Author

Bhagwat, Anand S., Torres, Leonel, Shestova, Olga, Shestov, Maksim, Mellors, Patrick W., Fisher, Han R., Farooki, Saamia N., Frost, Benjamin F., Loken, Michael R., Gaymon, Avery L., Frazee, Diane, Rogal, Walter, Frey, Noelle, Hexner, Elizabeth O., Luger, Selina M., Loren, Alison W., Martin, Mary Ellen, McCurdy, Shannon R., Perl, Alexander E., Stadtmauer, Edward A., Brogdon, Jennifer L., Fraietta, Joseph A., Hwang, Wei-Ting, Siegel, Don L., Plesa, Gabriela, Aplenc, Richard, Porter, David L., June, Carl H., and Gill, Saar I.

Published
2024
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3. Intrathecal bivalent CAR T cells targeting EGFR and IL13Rα2 in recurrent glioblastoma: phase 1 trial interim results

Author

Bagley, Stephen J., Logun, Meghan, Fraietta, Joseph A., Wang, Xin, Desai, Arati S., Bagley, Linda J., Nabavizadeh, Ali, Jarocha, Danuta, Martins, Rene, Maloney, Eileen, Lledo, Lester, Stein, Carly, Marshall, Amy, Leskowitz, Rachel, Jadlowsky, Julie K., Christensen, Shannon, Oner, Bike Su, Plesa, Gabriela, Brennan, Andrea, Gonzalez, Vanessa, Chen, Fang, Sun, Yusha, Gladney, Whitney, Barrett, David, Nasrallah, MacLean P., Hwang, Wei-Ting, Ming, Guo-Li, Song, Hongjun, Siegel, Donald L., June, Carl H., Hexner, Elizabeth O., Binder, Zev A., and O’Rourke, Donald M.

Published
2024
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5. Repeated peripheral infusions of anti-EGFRvIII CAR T cells in combination with pembrolizumab show no efficacy in glioblastoma: a phase 1 trial

Author

Bagley, Stephen J., Binder, Zev A., Lamrani, Lamia, Marinari, Eliana, Desai, Arati S., Nasrallah, MacLean P., Maloney, Eileen, Brem, Steven, Lustig, Robert A., Kurtz, Goldie, Alonso-Basanta, Michelle, Bonté, Pierre-Emmanuel, Goudot, Christel, Richer, Wilfrid, Piaggio, Eliane, Kothari, Shawn, Guyonnet, Lea, Guerin, Coralie L., Waterfall, Joshua J., Mohan, Suyash, Hwang, Wei-Ting, Tang, Oliver Y., Logun, Meghan, Bhattacharyya, Meghna, Markowitz, Kelly, Delman, Devora, Marshall, Amy, Wherry, E. John, Amigorena, Sebastian, Beatty, Gregory L., Brogdon, Jennifer L., Hexner, Elizabeth, Migliorini, Denis, Alanio, Cecile, and O’Rourke, Donald M.

Published
2024
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6. Changing Treatment and Metastatic Disease Patterns in Patients with EGFR Mutated NSCLC: An Academic Thoracic Medical Investigator’s Consortium Registry Analysis

Author

Stalker, Margaret, Grady, Connor B., Watts, Alex, Hwang, Wei-Ting, Chandrasekhara, Krishna, Sun, Fangdi, Liu, Geoffrey, Patel, Devalben, Nieva, Jorge, Herrmann, Amanda, Marrone, Kristen, Lam, Vincent K., Velcheti, Vamsidhar, Liu, Stephen V., Bravo Montenegro, Gabriela Liliana, Tompkins, William, Patil, Tejas, Weiss, Jared, Miller, Kelsey Leigh, Schwartzman, William, Dowell, Jonathan E., Shaverdashvili, Khvaramze, Villaruz, Liza, Cass, Amanda, Iams, Wade, Aisner, Dara, Aggarwal, Charu, Camidge, D. Ross, Sun, Lova, and Marmarelis, Melina E.

Published
2025
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7. Characteristics of Long-Term Survivors With EGFR-Mutant Metastatic NSCLC

Author

Tompkins, William, Grady, Connor B., Hwang, Wei-Ting, Chandrasekhara, Krishna, McCoach, Caroline, Sun, Fangdi, Liu, Geoffrey, Patel, Devalben, Nieva, Jorge, Herrmann, Amanda, Marrone, Kristen, Lam, Vincent K., Velcheti, Vamsi, Liu, Stephen V., Montenegro, Gabriela Liliana Bravo, Patil, Tejas, Weiss, Jared, Miller, Kelsey Leigh, Schwartzman, William, Dowell, Jonathan E., Shaverdashvili, Khvaramze, Villaruz, Liza, Cass, Amanda, Iams, Wade, Aisner, Dara, Aggarwal, Charu, Camidge, D. Ross, Marmarelis, Melina E., and Sun, Lova

Published
2024
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8. CHK1 inhibitor SRA737 is active in PARP inhibitor resistant and CCNE1 amplified ovarian cancer

Author

Xu, Haineng, Gitto, Sarah B., Ho, Gwo-Yaw, Medvedev, Sergey, Shield-Artin, Kristy, Kim, Hyoung, Beard, Sally, Kinose, Yasuto, Wang, Xiaolei, Barker, Holly E., Ratnayake, Gayanie, Hwang, Wei-Ting, Hansen, Ryan J., Strouse, Bryan, Milutinovic, Snezana, Hassig, Christian, Wakefield, Matthew J., Vandenberg, Cassandra J., Scott, Clare L., and Simpkins, Fiona

Published
2024
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9. Long-term stability of clinical-grade lentiviral vectors for cell therapy

Author

Jadlowsky, Julie K., Leskowitz, Rachel, McKenna, Stephen, Karar, Jayashree, Ma, Yujie, Dai, Anlan, Plesa, Gabriela, Chen, Fang, Alexander, Kathleen, Petrella, Jennifer, Gong, Nan, Hwang, Wei-Ting, Farrelly, Olivia, Barber-Rotenberg, Julie, Christensen, Shannon, Gonzalez, Vanessa E., Chew, Anne, Fraietta, Joseph A., and June, Carl H.

Published
2024
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12. Anti-CD19 CAR T cells in combination with ibrutinib for the treatment of chronic lymphocytic leukemia

Author

Gill, Saar, Vides, Vanessa, Frey, Noelle V., Hexner, Elizabeth O., Metzger, Susan, O'Brien, Megan, Hwang, Wei-Ting, Brogdon, Jennifer L., Davis, Megan M., Fraietta, Joseph A., Gaymon, Avery L., Gladney, Whitney L., Lacey, Simon F., Lamontagne, Anne, Mato, Anthony R., Maus, Marcela V., Melenhorst, J. Joseph, Pequignot, Edward, Ruella, Marco, Shestov, Maksim, Byrd, John C., Schuster, Stephen J., Siegel, Donald L., Levine, Bruce L., June, Carl H., and Porter, David L.

Published
2022
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13. Patterns of Use, Outcomes, and Resource Utilization among Recipients of Commercial Axicabtagene Ciloleucel and Tisagenlecleucel for Relapsed/Refractory Aggressive B Cell Lymphomas

Author

Riedell, Peter A., Hwang, Wei-Ting, Nastoupil, Loretta J., Pennisi, Martina, McGuirk, Joseph P., Maziarz, Richard T., Bachanova, Veronika, Oluwole, Olalekan O., Brower, Jamie, Flores, Oscar A., Ahmed, Nausheen, Schachter, Levanto, Bharucha, Kharmen, Dholaria, Bhagirathbhai R., Schuster, Stephen J., Perales, Miguel-Angel, Bishop, Michael R., and Porter, David L.

Published
2022
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15. Real-world effectiveness of CPX-351 vs venetoclax and azacitidine in acute myeloid leukemia

Author

Matthews, Andrew H., Perl, Alexander E., Luger, Selina M., Loren, Alison W., Gill, Saar I., Porter, David L., Babushok, Daria V., Maillard, Ivan P., Carroll, Martin P., Frey, Noelle V., Hexner, Elizabeth O., Martin, Mary Ellen, McCurdy, Shannon R., Stadtmauer, Edward A., Paralkar, Vikram R., Bruno, Ximena Jordan, Hwang, Wei-Ting, Margolis, David, and Pratz, Keith W.

Published
2022
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17. Determining Line of Therapy from Real‐World Data in Non‐Small Cell Lung Cancer.

Author

Grady, Connor B., Hwang, Wei‐Ting, Reuss, Joshua E., Iams, Wade, Cass, Amanda, Liu, Geoffrey, Patel, Devalben, Liu, Stephen V., Montenegro, Gabriela Liliana Bravo, Patil, Tejas, Nieva, Jorge J., Herrmann, Amanda, Marrone, Kristen A., Lam, Vincent K., Schwartzman, William, Dowell, Jonathan, Villaruz, Liza C., Miller, Kelsey Leigh, Weiss, Jared, and Sun, Fangdi

Abstract

Introduction: Determining lines of therapy (LOT) using real‐world data is crucial to inform clinical decisions and support clinical research. Existing rules for determining LOT in patients with metastatic non‐small cell lung cancer (mNSCLC) do not incorporate the growing number of targeted therapies used in treatment today. Therefore, we propose rules for determining LOT from real‐world data of patients with mNSCLC treated with targeted therapies. Methods: LOT rules were developed through expert consensus using a real‐world cohort of 550 patients with ALK+ or ROS1+ mNSCLC in the multi‐institutional, electronic medical record‐based Academic Thoracic Oncology Medical Investigators Consortium's (ATOMIC) Driver Mutation Registry. Rules were subsequently modified based on a review of appropriate LOT determination. These resulting rules were then applied to an independent cohort of patients with EGFR+ mNSCLC to illustrate their use. Results: Six rules for determining LOTs were developed. Among 1133 patients with EGFR mutations and mNSCLC, a total of 3168 regimens were recorded with a median of 2 regimens per patient (IQR, 1–4; range, 1–13). After applying our rules, there were 2834 total LOTs with a median of 2 LOTs per patient (IQR, 1–3; range, 1–11). Rules 1–3 kept 11% of regimen changes from advancing the LOT. When compared to previously published rules, LOT assignments differed 5.7% of the time, mostly in LOTs with targeted therapy. Conclusion: These rules provide an updated framework to evaluate current treatment patterns, accounting for the increased use of targeted therapies in patients with mNSCLC, and promote standardization of methods for determining LOT from real‐world data. [ABSTRACT FROM AUTHOR]

Published
2024
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18. Electronic Medical Record–Based Nudge Intervention to Increase Comprehensive Molecular Genotyping in Patients With Metastatic Non–Small Cell Lung Cancer: Results From a Prospective Clinical Trial.

Author

Marmarelis, Melina E., Scholes, Dylan G., McWilliams, Tara L., Hwang, Wei-Ting, Kosteva, John, Costello, Michael R., Sun, Lova, Singh, Aditi P., Lau-Min, Kelsey S., Doucette, Abigail, Gabriel, Peter E., Martella, Anthony O., Roy, Megan A., Thompson, Jeffrey C., Cohen, Roger B., Dougherty, David W., Shulman, Lawrence N., Langer, Corey J., Bekelman, Justin E., and Carpenter, Erica L.

Subjects
PEARSON correlation (Statistics), RESEARCH funding, ACADEMIC medical centers, EVALUATION of human services programs, CLINICAL trials, FISHER exact test, PROBABILITY theory, ONCOLOGY, EVALUATION of medical care, CHI-squared test, MANN Whitney U Test, DESCRIPTIVE statistics, METASTASIS, LONGITUDINAL method, ELECTRONIC health records, LUNG cancer, CONFIDENCE intervals, DATA analysis software, MOLECULAR diagnosis, GENOTYPES, MEDICAL referrals
Abstract

PURPOSE: Less than half of the patients with newly diagnosed metastatic non–small cell lung cancer (NSCLC) undergo comprehensive molecular testing. We designed an electronic medical record (EMR)–based "nudge intervention" to prompt plasma-based molecular testing at the time of initial medical oncology consultation. METHODS: A nonrandomized prospective trial was conducted at the University of Pennsylvania's academic practice and two affiliated community practices. Molecular genotyping was performed by tissue- and/or plasma-based next generation sequencing methods. Comprehensive testing was defined as testing for EGFR , ALK , BRAF , ROS1 , MET , RET , KRAS , and NTRK. Guideline-concordant treatment was defined as the use of the appropriate first-line (1L) therapy as per the National Comprehensive Cancer Network (NCCN) guidelines. Proportion of patients with comprehensive molecular genotyping results available at any time, molecular results available before 1L therapy, and guideline-concordant 1L treatment were compared between the preintervention and postintervention cohorts using Fisher's exact test or Pearson's chi-squared test. RESULTS: Five hundred and thirty-three patients were included, 376 in the preintervention cohort and 157 in the postintervention cohort. After implementation of the EMR-based nudge, a higher proportion of patients underwent comprehensive molecular testing in the postintervention versus the preintervention cohort (100% v 88%, P = <.001), had results of comprehensive molecular testing available before initiating 1L treatment (97.3% v 91.6%, P =.026), and received NCCN guideline-concordant care (89.8% v 78.2%, P =.035). CONCLUSION: Across three practice sites in a large health system, implementation of a provider team–focused EMR-based nudge intervention was feasible, and led to a higher number of patients with NSCLC undergoing comprehensive molecular genotyping. These findings demonstrate that behavioral nudges can promote molecular testing and should be studied further as a tool to improve guideline-concordant care in both community and academic sites. [ABSTRACT FROM AUTHOR]

Published
2024
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19. Association Between Availability of Molecular Genotyping Results and Overall Survival in Patients With Advanced Nonsquamous Non–Small-Cell Lung Cancer

Author

Aggarwal, Charu, Marmarelis, Melina E., Hwang, Wei-Ting, Scholes, Dylan G., McWilliams, Tara L., Singh, Aditi P., Sun, Lova, Kosteva, John, Costello, Michael R., Cohen, Roger B., Langer, Corey J., Doucette, Abigail, Gabriel, Peter N., Shulman, Lawrence N., Rendle, Katharine A., Thompson, Jeffrey C., Bekelman, Justin E., and Carpenter, Erica L.

Published
2023
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20. PSMA-targeting TGFβ-insensitive armored CAR T cells in metastatic castration-resistant prostate cancer: a phase 1 trial

Author

Narayan, Vivek, Barber-Rotenberg, Julie S., Jung, In-Young, Lacey, Simon F., Rech, Andrew J., Davis, Megan M., Hwang, Wei-Ting, Lal, Priti, Carpenter, Erica L., Maude, Shannon L., Plesa, Gabriela, Vapiwala, Neha, Chew, Anne, Moniak, Michael, Sebro, Ronnie A., Farwell, Michael D., Marshall, Amy, Gilmore, Joan, Lledo, Lester, Dengel, Karen, Church, Sarah E., Hether, Tyler D., Xu, Jun, Gohil, Mercy, Buckingham, Thomas H., Yee, Stephanie S., Gonzalez, Vanessa E., Kulikovskaya, Irina, Chen, Fang, Tian, Lifeng, Tien, Kyle, Gladney, Whitney, Nobles, Christopher L., Raymond, Hayley E., Hexner, Elizabeth O., Siegel, Donald L., Bushman, Frederic D., June, Carl H., Fraietta, Joseph A., and Haas, Naomi B.

Published
2022
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23. Combination ATR and PARP Inhibitor (CAPRI): A phase 2 study of ceralasertib plus olaparib in patients with recurrent, platinum-sensitive epithelial ovarian cancer (cohort A).

Author

Simpkins, Fiona, primary, Nasioudis, Dimitrios, additional, Wethington, Stephanie L., additional, Martin, Lainie P., additional, Tanyi, Janos Laszlo, additional, Latif, Nawar A., additional, Torigian, Drew A., additional, Omran, Dalia K., additional, Rodriguez, Diego, additional, Smith, Simon, additional, Dean, Emma, additional, Domchek, Susan M., additional, Drapkin, Ronny, additional, Shih, Ie-Ming, additional, Brown, Eric J, additional, Hwang, Wei-Ting, additional, Armstrong, Deborah Kay, additional, Gaillard, Stephanie, additional, Giuntoli, Robert Lawrence, additional, and Liu, Joyce F., additional

Published
2024
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25. Combination ATR and PARP Inhibitor (CAPRI): A phase 2 study of ceralasertib plus olaparib in patients with recurrent, platinum-resistant epithelial ovarian cancer

Author

Shah, Payal D., Wethington, Stephanie L., Pagan, Cheyenne, Latif, Nawar, Tanyi, Janos, Martin, Lainie P., Morgan, Mark, Burger, Robert A., Haggerty, Ashley, Zarrin, Haley, Rodriguez, Diego, Domchek, Susan, Drapkin, Ronny, Shih, Ie-Ming, Smith, Simon A., Dean, Emma, Gaillard, Stéphanie, Armstrong, Deborah, Torigian, Drew A., Hwang, Wei-Ting, Giuntoli, Robert, and Simpkins, Fiona

Published
2021
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26. CCNE1 copy number is a biomarker for response to combination WEE1-ATR inhibition in ovarian and endometrial cancer models

Author

Xu, Haineng, George, Erin, Kinose, Yasuto, Kim, Hyoung, Shah, Jennifer B., Peake, Jasmine D., Ferman, Benjamin, Medvedev, Sergey, Murtha, Thomas, Barger, Carter J., Devins, Kyle M., D’Andrea, Kurt, Wubbenhorst, Bradley, Schwartz, Lauren E., Hwang, Wei-Ting, Mills, Gordon B., Nathanson, Katherine L., Karpf, Adam R., Drapkin, Ronny, Brown, Eric J., and Simpkins, Fiona

Published
2021
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27. Framework for assessment and phytoremediation of asbestos-contaminated sites

Author

Gonneau, Cédric, Miller, Kinsey, Mohanty, Sanjay K, Xu, Rengyi, Hwang, Wei-Ting, Willenbring, Jane K, and Casper, Brenda B

Subjects
Environmental Sciences, Environmental Management, Pollution and Contamination, Asbestos, Biodegradation, Environmental, Biomass, Environmental Monitoring, Metals, Heavy, Plant Development, Poaceae, Soil, Soil Pollutants, United States, ASTMmethod, Crop cultivar, Heavy metal, Native grass, Phytostabilization, Size fraction, ASTM method, Chemical Sciences, Biological Sciences
Abstract

We examine the feasibility of phytoremediation as an alternative strategy to limit the exposure of asbestos in site with asbestos-containing materials. We collected soils from four locations from two sites-one with naturally occurring asbestos, and another, a superfund site, where asbestos-containing materials were disposed over decades-and performed ecotoxicology tests. We also performed two experiments with crop cultivar and two grasses from serpentine ecotype and cultivar to determined best choice for phytoremediation. Asbestos concentrations in different size fractions of soils varied by orders of magnitude. However, different asbestos concentrations had little effect on germination and root growth. Presence of co-contaminants such as heavy metals and lack of nutrients affected plant growth to different extents, indicating that several of these limiting factors should be considered instead of the primary contaminant of concern. Crop cultivar survived on asbestos-contaminated soil. Grasses from serpentine ecotype did not show higher biomass than the cultivar. Overall, these results showed that soil conditions play a critical role in screening different crop species for phytoremediation and that asbestos concentration has limited to no effect on plant growth. Our study provided a framework for phytoremediation of asbestos-contaminated sites to limit long-term asbestos exposure.

Published
2017

28. Differential elemental uptake in three pseudo-metallophyte C4 grasses in situ in the eastern USA

Author

Gonneau, Cédric, Mohanty, Sanjay K, Dietterich, Lee H, Hwang, Wei-Ting, Willenbring, Jane K, and Casper, Brenda B

Subjects
Environmental Sciences, Pollution and Contamination, C-4 grass, accumulation, excluder, Serpentine, Calamine, Pseudo-metallophytes, C4 grass, accumulation, excluder, Biological Sciences, Agricultural and Veterinary Sciences, Agronomy & Agriculture, Agricultural, veterinary and food sciences, Biological sciences, Environmental sciences
Abstract

Background and aimsElemental uptake in serpentine floras in eastern North America is largely unknown. The objective of this study was to determine major and trace element concentrations in soil and leaves of three native pseudo-metallophyte C4 grasses in situ at five sites with three very different soil types, including three serpentine sites, in eastern USA.MethodsPseudo-total and extractible concentrations of 15 elements were measured and correlated from the soils and leaves of three species at the five sites.ResultsElement concentrations in soils of pseudo-metallophytes varied up to five orders of magnitude. Soils from metalliferous sites exhibited higher concentrations of their characteristic elements than non-metalliferous. In metallicolous populations, elemental concentrations depended on the element. Concentrations of major elements (Ca, Mg, K) in leaves were lower than typical toxicity thresholds, whereas concentrations of Zn were higher.ConclusionsIn grasses, species can maintain relatively low metal concentrations in their leaves even when soil concentrations are richer. However, in highly Zn-contaminated soil, we found evidence of a threshold concentration above which Zn uptake increases drastically. Finally, absence of main characteristics of serpentine soil at one site indicated the importance of soil survey and restoration to maintain serpentinophytes communities and avoid soil encroachment.

Published
2017

34. Multianalyte Prognostic Signature Including Circulating Tumor DNA and Circulating Tumor Cells in Patients With Advanced Pancreatic Adenocarcinoma

Author

Chapin, William J., Till, Jacob E., Hwang, Wei-Ting, Eads, Jennifer R., Karasic, Thomas B., OʼDwyer, Peter J., Schneider, Charles J., Teitelbaum, Ursina R., Romeo, Janae, Black, Taylor A., Christensen, Theresa E., Redlinger Tabery, Colleen, Anderson, Amanda, Slade, Megan, LaRiviere, Michael, Yee, Stephanie S., Reiss, Kim A., OʼHara, Mark H., and Carpenter, Erica L.

Published
2022
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35. CAR T-Cell Immunotherapy in Minority Patients with Lymphoma

Author

Ghilardi, Guido, primary, Williamson, Staci, additional, Pajarillo, Raymone, additional, Paruzzo, Luca, additional, Chen, Linhui, additional, Grady, Connor, additional, Doucette, Abigail, additional, Nemecek, Eneida, additional, Gabrielli, Giulia, additional, Barta, Stefan K., additional, Svoboda, Jakub, additional, Chong, Elise A., additional, Yelton, Rebecca, additional, Nasta, Sunita D., additional, Landsburg, Daniel J., additional, Ugwuanyi, Ositadimma, additional, Chen, Andy I., additional, Schachter, Levanto, additional, White, Griffin, additional, Ballard, Hatcher J., additional, Weber, Elizabeth, additional, Curley, Cara, additional, Porter, David L., additional, Garfall, Alfred L., additional, Hwang, Wei-Ting, additional, Guerra, Carmen E., additional, Maziarz, Richard T., additional, Schuster, Stephen J., additional, and Ruella, Marco, additional

Published
2024
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36. Characteristics of long-term survivors with EGFR mutant (EGFRm) metastatic non-small cell lung cancer (mNSCLC)

Author

Tompkins, William, primary, Grady, Connor B., additional, Hwang, Wei-Ting, additional, Chandrasekhara, Krishna, additional, McCoach, Caroline, additional, Sun, Fangdi, additional, Liu, Geoffrey, additional, Patel, Devalben, additional, Nieva, Jorge, additional, Herrmann, Amanda, additional, Marrone, Kristen, additional, Lam, Vincent K., additional, Velcheti, Vamsi, additional, Liu, Stephen V., additional, Bravo Montenegro, Gabriela Liliana, additional, Patil, Tejas, additional, Weiss, Jared, additional, Miller, Kelsey Leigh, additional, Schwartzman, William, additional, Dowell, Jonathan E., additional, Shaverdashvili, Khvaramze, additional, Villaruz, Liza, additional, Cass, Amanda, additional, Iams, Wade, additional, Aisner, Dara, additional, Aggarwal, Charu, additional, Camidge, D. Ross, additional, Marmarelis, Melina E., additional, and Sun, Lova, additional

Published
2024
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37. Monitoring Integration over Time Supports a Role for Cytotoxic T Lymphocytes and Ongoing Replication as Determinants of Reservoir Size

Author

Pinzone, Marilia Rita, Graf, Erin, Lynch, Lindsay, McLaughlin, Brigit, Hecht, Frederick M, Connors, Mark, Migueles, Stephen A, Hwang, Wei-Ting, Nunnari, Giuseppe, and O'Doherty, Una

Subjects
Medical Microbiology, Biomedical and Clinical Sciences, Immunology, HIV/AIDS, Infectious Diseases, Clinical Research, Infection, Good Health and Well Being, Acute Disease, Anti-HIV Agents, Chronic Disease, DNA, Viral, Disease Reservoirs, HIV, HIV Infections, Humans, Longitudinal Studies, T-Lymphocytes, Cytotoxic, Viral Load, Virus Integration, Virus Replication, Biological Sciences, Agricultural and Veterinary Sciences, Medical and Health Sciences, Virology, Agricultural, veterinary and food sciences, Biological sciences, Biomedical and clinical sciences
Abstract

The dynamics of HIV reservoir accumulation off antiretroviral therapy (ART) is underexplored. Levels of integrated HIV DNA in peripheral blood mononuclear cells (PBMCs) were longitudinally monitored before and after antiviral therapy. HIV integration increased over time in both elite controllers (ECs; n = 8) and noncontrollers (NCs; n = 6) before ART, whereas integration remained stable in patients on ART (n = 4). The median annual fold change was higher in NCs than in ECs and negatively correlated with CD4/CD8 T-cell ratio. Cytotoxic T lymphocyte (CTL) function as assessed by infected CD4 T-cell elimination (ICE) and granzyme B activity did not significantly change over time in ECs, suggesting that the gradual increase in integrated HIV DNA observed in ECs was not a result of progressive loss of immune-mediated control. Also, acutely infected (n = 7) but not chronically infected (n = 6) patients exhibited a significant drop in integrated HIV DNA 12 months after ART initiation. In conclusion, in the absence of ART, integrated HIV accumulates over time both in NCs and in ECs, at variable individual rates. Starting ART early in infection leads to a greater drop in integrated HIV DNA than does initiating treatment after years of infection. The increase in integrated HIV DNA over time suggests that early treatment may be of benefit in limiting HIV reservoirs.ImportanceThe establishment of a latent reservoir represents a barrier to cure among HIV-infected individuals. The dynamics of HIV reservoir accumulation over time in patients before antiviral therapy is underexplored, in large part because it is difficult to accurately and reproducibly measure the size of HIV reservoir in this setting. In our study, we compared the dynamics of integrated HIV DNA over time in ECs and NCs before and after ART was initiated. We found that integrated HIV DNA levels progressively increase over time in the absence of ART, but with a higher, albeit variable, rate in NCs compared to ECs. In addition, integrated HIV DNA declines more dramatically when ART is initiated in acute rather than chronic HIV infection, suggesting important differences between acute and chronic infection. Our study highlights the role of HIV replication and CTL control in reservoir accumulation in sanctuary sites and why ART appears to be more effective in acute infection.

Published
2016

48. CTIM-40. EARLY RADIOGRAPHIC RESPONSE AND ENGRAFTMENT OF PHASE I FIRST-IN-HUMAN BICISTRONIC CAR T CELLS CORRELATE WITH REAL-TIME AUTOLOGOUS GBM ORGANOID CYTOLYSIS

Author

Logun, Meghan, primary, Bagley, Stephen J, additional, Wang, Xin, additional, Zhang, Daniel, additional, Sun, Yusha, additional, Ming, Guo-li, additional, Nabavizadeh, Ali, additional, Marshall, Amy, additional, Maloney, Eileen, additional, Hwang, Wei-Ting, additional, Fraietta, Joseph, additional, Gonzalez, Vanessa, additional, Desai, Arati, additional, Bagley, Linda, additional, Hexner, Elizabeth, additional, Nasrallah, MacLean P, additional, Song, Hongjun, additional, Binder, Zev, additional, and O'Rourke, Donald M, additional

Published
2023
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49. CTIM-24. REPEATED PERIPHERAL INFUSIONS OF ANTI-EGFRVIII CAR T CELLS IN COMBINATION WITH PEMBROLIZUMAB REMODELS THE TUMOR MICROENVIRONMENT IN DE NOVO GLIOBLASTOMA

Author

Binder, Zev, primary, Bagley, Stephen J, additional, Lamrani, Lamia, additional, Marinari, Eliana, additional, Desai, Arati, additional, Nasrallah, MacLean P, additional, Maloney, Eileen, additional, Brem, Steven, additional, Lustig, Robert A, additional, Kurtz, Goldie, additional, Alonso-Basanta, Michelle, additional, Bonte, Pierre-Emmanuel, additional, Goudot, Christel, additional, Richer, Wilfrid, additional, Piaggio, Eliane, additional, Kothari, Shawn, additional, Guyonnet, Lea, additional, Guerin, Coralie, additional, Waterfall, Joshua, additional, Mohan, Suyash, additional, Hwang, Wei-Ting, additional, Tang, Oliver, additional, Logun, Meghan, additional, Bhattacharyya, Meghna, additional, Markowitz, Kelly, additional, Delman, Devora, additional, Marshall, Amy, additional, Wherry, E John, additional, Amigorena, Sebastian, additional, Beatty, Gregory, additional, Brogdon, Jennifer, additional, Hexner, Elizabeth, additional, Migliorini, Denis, additional, Alanio, Cecile, additional, and O'Rourke, Donald M, additional

Published
2023
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