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207. Split decisions

Author

Levine, Bruce and Gray, Bill

Subjects
Rackets (Sporting goods) -- Product/service Evaluations
Published
2010

210. IDENTIFYING HIGHLY CONSERVED PATHOGENICITY GENES IN CHESTNUT BLIGHT AND POWDERY MILDEW FUNGI AS TARGETS FOR NOVEL FORMS OF HOST RESISTANCE

Author

Levine, Bruce Jonathan

Subjects
resistance, Molecular biology, chestnut, fungi, powdery, blight, Plant pathology, Plant sciences, genes, mildew
Abstract

A bioinformatic search of the genomes of chestnut blight fungus, Cryphonectria parasitica (Cp), and the Arabidopsis powdery mildew fungus, Golovinomyces cichoracearum (Gc), yielded six suspected pathogenicity genes with homologues in both species. Deletion of these genes by homologous gene replacement was attempted in Cp, with one success, TG4. The TG4-knockout strain showed changes in phenotype and reduced fungal virulence against chestnut. TG4 appears to be a promising target for host-induced gene silencing (HIGS) in transgenic American chestnut. The use of homologues from genetically tractable species like Cp can help overcome the obstacles to performing reverse genetics on intractable, biotrophic fungi such as Gc. Experiments underway involving the silencing and ectopic overexpression of the Gc homologues of the target genes provide a rapid method to study Cp genes, including to screen additional candidate genes as future targets for HIGS.

Published
2019
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212. A Method of Assembling Compact Coherent Fiber-Optic Bundles

Author

Martin, Stefan, Liu, Duncan, Levine, Bruce Martin, Shao, Michael, and Wallace, James

Subjects
Optics
Abstract

A method of assembling coherent fiber-optic bundles in which all the fibers are packed together as closely as possible is undergoing development. The method is based, straightforwardly, on the established concept of hexagonal close packing; hence, the development efforts are focused on fixtures and techniques for practical implementation of hexagonal close packing of parallel optical fibers.

Published
2007

218. Antiviral effect and ex vivo CD4+ T cell proliferation in HIV-positive patients as a result of CD28 costimulation

Author

Levine, Bruce L., Mosca, Joseph D., Riley, James L., Carroll, Richard G., Vahey, Maryanne T., Jagodzinski, Linda L., Wagner, Kenneth F., Mayers, Douglas L., Burke, Donald S., Weislow, Owen S., Louis, Daniel C. St., and June, Carl H.

Subjects
HIV (Viruses) -- Research, Gene therapy -- Research, CD4 lymphocytes -- Research, Science and technology, Research
Abstract

Because stimulation of [CD4.sup.+] lymphocytes leads to activation of human immunodeficiency virus-type 1 (HIV-1) replication, viral spread, and cell death, adoptive [CD4.sup.+] T cell therapy has not been possible. When antigen and CD28 receptors on cultured T cells were stimulated by monoclonal antibodies (mAbs) to CD3 and CD28 that had been immobilized, there was an increase in the number of polyclonal [CD4.sup.+] T cells from HIV-infected donors. Activated cells predominantly secreted cytokines associated with T helper cell type 1 function. The HIV-1 viral load declined in the absence of antiretroviral agents. Moreover, CD28 stimulation of [CD4.sup.+] T cells from uninfected donors rendered these cells highly resistant to HIV-1 infection. Immobilization of CD28 mAb was crucial to the development of HIV resistance, as cells stimulated with soluble CD28 mAb were highly susceptible to HIV infection. The CD28-mediated antiviral effect occurred early in the viral life cycle, before HIV-1 DNA integration. These data may facilitate immune reconstitution and gene therapy approaches in persons with HIV infection., [CD4.sup.+] T cells contain the major reservoir of HIV-1 in vivo (1, 2). The difficulties involved in inducing proliferation in vitro of autologous [CD4.sup.+] T cells from patients with HIV-1 [...]

Published
1996

219. Cancer Killers.

Author

Posey, Avery D. Jr., June, Carl H., and Levine, Bruce L.

Subjects
CANCER immunotherapy, SYNTHETIC biology, IMMUNE system, CHIMERIC antigen receptors, T cells, CANCER treatment, GENE therapy, CHARTS, diagrams, etc., THERAPEUTICS
Abstract

The article discusses the development of synthetic immune chimeric antigen receptor T (CAR T) cells as a treatment for cancer, including through offering a diagram. An overview of the genetic engineering of CAR T cells to treat cancer, including the genetic modification of T cells to target the antigen, is provided.

Published
2017
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220. A nulling coronagraph for TPF-C

Author

Shao, Michael, Levine, Bruce Martin, Wallace, James Kent, Orton, Glenn S, Schmidtlin, Edouard, Lane, Benjamin F, Seager, Sara, Tolls, Volker, Lyon, Richard G, Samuele, Rocco, Tenerelli, Domenick J, Woodruff, Robert, and Ge, Jian

Published
2006

223. White-Light Nulling Interferometers for Detecting Planets

Author

Mennesson, Bertrand, Serabyn, Eugene, Shao, Michael, and Levine, Bruce

Subjects
Man/System Technology And Life Support
Abstract

A report proposes the development of a white-light nulling interferometer to be used in conjunction with a singleaperture astronomical telescope that would be operated in outer space. When such a telescope is aimed at a given star, the interferometer would suppress the light of that star while passing enough light from planets (if any) orbiting the star, to enable imaging or spectroscopic examination of the planets. In a nulling interferometer, according to the proposal, scattered light would be suppressed by spatial filtering in an array of single-mode optical fibers rather than by requiring optical surfaces to be accurate within 1/4,000 wavelength as in a coronagraph or an apodized telescope. As a result, angstrom-level precision would be needed in only the small nulling combiner, and not in large, meter-sized optics. The nulling interferometer could work as an independent instrument in space or in conjunction with a coronagraphic system to detect planets outside our solar system.

Published
2004

224. THE GAME I'LL NEVER FORGET.

Author

HERNANDEZ, KEITH, Levine, Bruce, and Bierig, Joel

Subjects
BASEBALL competitions, HOME field advantage (Sports)
Abstract

But after Rick Aguilera - the second of just four pitchers used by Mets manager Davey Johnson - retired Houston in the bottom half, the Mets went to work in the top of the ninth. Houston had scored three first-inning runs off Mets starter Bob Ojeda, with Astros lefty Bob Knepper taking it from there. As told to Bruce Levine and Joel Bierig In the game he'll never forget - Game 6 of the 1986 National League Championship Series between his New York Mets and the Houston Astros - Keith Hernandez was, in a word, nervous. But a Houston Oilers football game posed a conflict with an Astrodome Game 4; so home-field advantage was awarded to the Astros. [Extracted from the article]

Published
2022

225. A randomized phase 2 trial of idiotype vaccination and adoptive autologous T-cell transfer in patients with multiple myeloma

Author

Qazilbash, Muzaffar H., Saini, Neeraj Y., Cha, Soung-chul, Wang, Zhe, Stadtmauer, Edward A., Baladandayuthapani, Veerabhadran, Lin, Heather, Tross, Beryl, Honhar, Medhavi, Rao, Sheetal S., Kim, Kunhwa, Popescu, Michael, Szymura, Szymon, Zhang, Tiantian, Anderson, Aaron, Bashir, Qaiser, Shpall, Elizabeth J., Orlowski, Robert Z., Levine, Bruce L., Kerr, Naseem, Garfall, Alfred, Cohen, Adam, Vogl, Dan T., Dengel, Karen, June, Carl H., Champlin, Richard, and Kwak, Larry W.

Abstract

We hypothesized that combining adoptively transferred autologous T cells with a cancer vaccine strategy would enhance therapeutic efficacy by adding antimyeloma idiotype (Id)–keyhole limpet hemocyanin (KLH) vaccine to vaccine-specific costimulated T cells. In this randomized phase 2 trial, patients received either control (KLH only) or Id-KLH vaccine, autologous transplantation, vaccine-specific costimulated T cells expanded ex vivo, and 2 booster doses of assigned vaccine. In 36 patients (KLH, n = 20; Id-KLH, n = 16), no dose-limiting toxicity was seen. At last evaluation, 6 (30%) and 8 patients (50%) had achieved complete remission in KLH-only and Id-KLH arms, respectively (P = .22), and no difference in 3-year progression-free survival was observed (59% and 56%, respectively; P = .32). In a 594 Nanostring nCounter gene panel analyzed for immune reconstitution (IR), compared with patients receiving KLH only, there was a greater change in IR genes in T cells in those receiving Id-KLH relative to baseline. Specifically, upregulation of genes associated with activation, effector function induction, and memory CD8+ T-cell generation after Id-KLH but not after KLH control vaccination was observed. Similarly, in responding patients across both arms, upregulation of genes associated with T-cell activation was seen. At baseline, all patients had greater expression of CD8+ T-cell exhaustion markers. These changes were associated with functional Id-specific immune responses in a subset of patients receiving Id-KLH. In conclusion, in this combination immunotherapy approach, we observed significantly more robust IR in CD4+ and CD8+ T cells in the Id-KLH arm, supporting further investigation of vaccine and adoptive immunotherapy strategies. This trial was registered at www.clinicaltrials.gov as #NCT01426828.

Published
2022
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226. THE GAME I’LL NEVER FORGET.

Author

KAAT, JIM, Levine, Bruce, and Bierig, Joel

Subjects
GAMES, PRESEASON (Sports), BASEBALL, RECOLLECTION (Psychology)
Abstract

To many, Kaat's most memorable game is his route-going 5-1 victory over Koufax in Game 2 of the '65 Fall Classic. In late-September 1965, a 26year-old left-hander named Jim Kaat pitched the Minnesota Twins to their first American League pennant. Kaat, part of a strong rotation that included veterans Jim "Mudcat" Grant (team-high 21 victories), Jim Perry and Camilo Pascual, was 16-11 toward a final mark of 18-11 and a 2.83 ERA. Kaat's Twins fell to the great left-hander Sandy Koufax and the Los Angeles Dodgers in the '65 Fall Classic. [Extracted from the article]

Published
2022

228. Planet detection and spectroscopy in visible light with a single aperture telescope and a nulling coronagraph

Author

Shao, Michael, Serabyn, Eugene, Levine, Bruce Martin, Beichman, Charles, Liu, Duncan, Martin, Stefan, Orton, Glen, Mennesson, Bertrand, Morgan, Rhonda, Velusamy, Thangasamy, Wallace, J. Kent, and Unwin, Stephen

Subjects
Astronomy
Abstract

This talk describes a new concept for visible direct detection of Earth like extra solar planets using a nulling coronagraph instrument behind a 4m telescope in space. In the baseline design, a 4 beam nulling interferometer is synthesized from the telescope pupil, producing a very deep theta^4null which is then filtered by a coherent array of single mode fibers to suppress the residual scattered light. With perfect optics, the stellar leakage is less than 1e-11 of the starlight at the location of the planet. With diffraction limited telescope optics (lambda/20), suppression of the starlight to ~1e-10 is possible. The concept is described along with the key advantages over more traditional approaches such as apodized aperture telescopes and Lyot type coronagraphs.

Published
2003

229. Sedation of Children

Author

Drum, Elizabeth, Herlich, Andrew, Levine, Bruce, and Mayhew, James

Published
2001

230. Adoptive transfer of costimulated T cells induces lymphocytosis in patients with relapsed/refractory non-Hodgkin lymphoma following CD34+-selected hematopoietic cell transplantation

Author

Laport, Ginna G., Levine, Bruce L., Stadtmauer, Edward A., Schuster, Stephen J., Luger, Selina M., Grupp, Stephan, Bunin, Nancy, Strobl, Frank J., Cotte, Julio, Zheng, Zhaohui, Gregson, Brian, Rivers, Patricia, Vonderheide, Robert H., Liebowitz, David N., Porter, David L., and June, Carl H.

Published
2003
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231. An issue of professional identity.

Author

Levine, Bruce

Subjects
Washburn University. School of Law -- Officials and employees, Law teachers -- Religious aspects, Jews -- Identity
Published
1992

235. Response to Anti-Bcma CAR T Cell Therapy Correlates with T Cell Exhaustion and Activation Status in T Cells at Baseline in Myeloma

Author

Wang, Meng, primary, Pruteanu, Iulian, additional, Cohen, Adam D., additional, Garfall, Alfred L., additional, Tian, Lifeng, additional, Lacey, Simon F, additional, Fraietta, Joseph A, additional, Brogdon, Jennifer, additional, Davis, Megan, additional, Gonzalez, Vanessa E., additional, Levine, Bruce L, additional, Siegel, Don L., additional, Milone, Michael C., additional, Stadtmauer, Edward A., additional, June, Carl H, additional, and Melenhorst, J. Joseph, additional

Published
2019
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236. Combination Anti-Bcma and Anti-CD19 CAR T Cells As Consolidation of Response to Prior Therapy in Multiple Myeloma

Author

Garfall, Alfred L., primary, Cohen, Adam D., additional, Lacey, Simon F, additional, Tian, Lifeng, additional, Hwang, Wei-Ting, additional, Vogl, Dan T., additional, Waxman, Adam, additional, Lancaster, Eric, additional, Nelson, Anne Marie, additional, Ferthio, Regina, additional, Fesnak, Andrew, additional, Lamontagne, Anne, additional, Brennan, Andrea, additional, Guilliams, Jamie, additional, Gladney, Whitney Lynn, additional, Melenhorst, J. Joseph, additional, Young, Regina M, additional, Siegel, Don L., additional, Levine, Bruce L, additional, Brogdon, Jennifer, additional, Isaacs, Randi E., additional, June, Carl H, additional, Milone, Michael C., additional, and Stadtmauer, Edward A., additional

Published
2019
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237. Identification and Validation of Predictive Biomarkers to CD19- and BCMA-Specific CAR T-Cell Responses in CAR T-Cell Precursors

Author

Wang, Meng, primary, Pruteanu, Iulian, primary, Cohen, Adam D., primary, Garfall, Alfred L, primary, Milone, Michael C., primary, Tian, Lifeng, primary, Gonzalez, Vanessa E., primary, Gill, Saar, primary, Frey, Noelle V., primary, Barrett, David M., primary, Ruella, Marco, primary, Lacey, Simon F, primary, Svoboda, Jakub, primary, Chong, Elise A., primary, Fraietta, Joseph A, primary, Davis, Megan, primary, Nasta, Sunita D, primary, Levine, Bruce L, primary, Siegel, Don L., primary, Maude, Shannon L., primary, Schuster, Stephen J., primary, Stadtmauer, Edward A., primary, Grupp, Stephan, primary, Porter, David L., primary, June, Carl H, primary, and Melenhorst, J. Joseph, primary

Published
2019
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238. Outcomes in Aggressive B-Cell Non-Hodgkin Lymphomas with Anti-CD19 CAR T-Cell (CTL019) Products Not Meeting Commercial Release Specifications

Author

Chong, Elise A., primary, Gerson, James N., primary, Landsburg, Daniel J., primary, Dwivedy Nasta, Sunita, primary, Svoboda, Jakub, primary, Porter, David L., primary, Dengel, Karen, primary, Siegel, Don L., primary, Gilmore, Joan, primary, Barta, Stefan K., primary, Levine, Bruce L, primary, June, Carl H, primary, and Schuster, Stephen J., primary

Published
2019
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239. Phase I Study of Lentiviral-Transduced Chimeric Antigen Receptor-Modified T Cells Recognizing Mesothelin in Advanced Solid Cancers

Author

Haas, Andrew R., primary, Tanyi, Janos L., additional, O’Hara, Mark H., additional, Gladney, Whitney L., additional, Lacey, Simon F., additional, Torigian, Drew A., additional, Soulen, Michael C., additional, Tian, Lifeng, additional, McGarvey, Maureen, additional, Nelson, Anne Marie, additional, Farabaugh, Caitlin S., additional, Moon, Edmund, additional, Levine, Bruce L., additional, Melenhorst, J. Joseph, additional, Plesa, Gabriela, additional, June, Carl H., additional, Albelda, Steven M., additional, and Beatty, Gregory L., additional

Published
2019
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240. T-cell phenotypes associated with effective CAR T-cell therapy in postinduction vs relapsed multiple myeloma

Author

Garfall, Alfred L., primary, Dancy, Ehren K., additional, Cohen, Adam D., additional, Hwang, Wei-Ting, additional, Fraietta, Joseph A., additional, Davis, Megan M., additional, Levine, Bruce L., additional, Siegel, Don L., additional, Stadtmauer, Edward A., additional, Vogl, Dan T., additional, Waxman, Adam, additional, Rapoport, Aaron P., additional, Milone, Michael C., additional, June, Carl H., additional, and Melenhorst, J. Joseph, additional

Published
2019
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242. B cell maturation antigen–specific CAR T cells are clinically active in multiple myeloma

Author

Cohen, Adam D., primary, Garfall, Alfred L., additional, Stadtmauer, Edward A., additional, Melenhorst, J. Joseph, additional, Lacey, Simon F., additional, Lancaster, Eric, additional, Vogl, Dan T., additional, Weiss, Brendan M., additional, Dengel, Karen, additional, Nelson, Annemarie, additional, Plesa, Gabriela, additional, Chen, Fang, additional, Davis, Megan M., additional, Hwang, Wei-Ting, additional, Young, Regina M., additional, Brogdon, Jennifer L., additional, Isaacs, Randi, additional, Pruteanu-Malinici, Iulian, additional, Siegel, Don L., additional, Levine, Bruce L., additional, June, Carl H., additional, and Milone, Michael C., additional

Published
2019
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243. Tisagenlecleucel Model‐Based Cellular Kinetic Analysis of Chimeric Antigen Receptor–T Cells

Author

Stein, Andrew M., primary, Grupp, Stephan A., additional, Levine, John E., additional, Laetsch, Theodore W., additional, Pulsipher, Michael A., additional, Boyer, Michael W., additional, August, Keith J., additional, Levine, Bruce L., additional, Tomassian, Lori, additional, Shah, Sweta, additional, Leung, Mimi, additional, Huang, Pai‐Hsi, additional, Awasthi, Rakesh, additional, Mueller, Karen Thudium, additional, Wood, Patricia A., additional, and June, Carl H., additional

Published
2019
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244. How the DSM Is Used in Clinical Practice

Author

First, Michael B., primary, Erlich, Matthew D., additional, Adler, David A., additional, Leong, Shirley, additional, Dixon, Lisa B., additional, Oslin, David W., additional, Goldman, Beth, additional, Koh, Steve, additional, Levine, Bruce, additional, Berlant, Jeffrey L., additional, and Siris, Samuel G., additional

Published
2019
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245. Anti-CD19 CAR T cells with high-dose melphalan and autologous stem cell transplantation for refractory multiple myeloma

Author

Garfall, Alfred L., primary, Stadtmauer, Edward A., additional, Hwang, Wei-Ting, additional, Lacey, Simon F., additional, Melenhorst, Jan Joseph, additional, Krevvata, Maria, additional, Carroll, Martin P., additional, Matsui, William H., additional, Wang, Qiuju, additional, Dhodapkar, Madhav V., additional, Dhodapkar, Kavita, additional, Das, Rituparna, additional, Vogl, Dan T., additional, Weiss, Brendan M., additional, Cohen, Adam D., additional, Mangan, Patricia A., additional, Ayers, Emily C., additional, Nunez-Cruz, Selene, additional, Kulikovskaya, Irina, additional, Davis, Megan M., additional, Lamontagne, Anne, additional, Dengel, Karen, additional, Kerr, Naseem D.S., additional, Young, Regina M., additional, Siegel, Donald L., additional, Levine, Bruce L., additional, Milone, Michael C., additional, Maus, Marcela V., additional, and June, Carl H., additional

Published
2019
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247. Optimizing parameters for clinical-scale production of high IL-12 secreting dendritic cells pulsed with oxidized whole tumor cell lysate

Author

Chiang Cheryl L-L, Maier Dawn A, Kandalaft Lana E, Brennan Andrea L, Lanitis Evripidis, Ye Qunrui, Levine Bruce L, Czerniecki Brian J, Powell Jr Daniel J, and Coukos George

Subjects
Medicine
Abstract

Abstract Background Dendritic cells (DCs) are the most potent antigen-presenting cell population for activating tumor-specific T cells. Due to the wide range of methods for generating DCs, there is no common protocol or defined set of criteria to validate the immunogenicity and function of DC vaccines. Methods Monocyte-derived DCs were generated during 4 days of culture with recombinant granulocyte-macrophage colony stimulating factor and interleukin-4, and pulsed with tumor lysate produced by hypochlorous acid oxidation of tumor cells. Different culture parameters for clinical-scale DC preparation were investigated, including: 1) culture media; 2) culture surface; 3) duration of activating DCs with lipopolysaccharide (LPS) and interferon (IFN)-gamma; 4) method of DC harvest; and 5) cryomedia and final DC product formulation. Results DCs cultured in CellGenix DC media containing 2% human AB serum expressed higher levels of maturation markers following lysate-loading and maturation compared to culturing with serum-free CellGenix DC media or AIM-V media, or 2% AB serum supplemented AIM-V media. Nunclon™Δ surface, but not Corning® tissue-culture treated surface and Corning® ultra-low attachment surface, were suitable for generating an optimal DC phenotype. Recombinant trypsin resulted in reduced major histocompatibility complex (MHC) Class I and II expression on mature lysate-loaded DCs, however presentation of MHC Class I peptides by DCs was not impaired and cell viability was higher compared to cell scraping. Preservation of DCs with an infusible cryomedia containing Plasma-Lyte A, dextrose, sodium chloride injection, human serum albumin, and DMSO yielded higher cell viability compared to using human AB serum containing 10% DMSO. Finally, activating DCs for 16 hours with LPS and IFN-γ stimulated robust mixed leukocyte reactions (MLRs), and high IL-12p70 production in vitro that continued for 24 hours after the cryopreserved DCs were thawed and replated in fresh media. Conclusions This study examined criteria including DC phenotype, viability, IL-12p70 production and the ability to stimulate MLR as metrics of whole oxidized tumor lysate-pulsed DC immunogenicity and functionality. Development and optimization of this unique method is now being tested in a clinical trial of autologous oxidized tumor lysate-pulsed DC in clinical-scale in recurrent ovarian, primary peritoneal or fallopian tube cancer (NCT01132014).

Published
2011
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248. Engineered artificial antigen presenting cells facilitate direct and efficient expansion of tumor infiltrating lymphocytes

Author

Coukos George, June Carl H, Riley James L, Suhoski Megan M, Levine Bruce L, Loisiou Maria, Ye Qunrui, and Powell Daniel J

Subjects
Medicine
Abstract

Abstract Background Development of a standardized platform for the rapid expansion of tumor-infiltrating lymphocytes (TILs) with anti-tumor function from patients with limited TIL numbers or tumor tissues challenges their clinical application. Methods To facilitate adoptive immunotherapy, we applied genetically-engineered K562 cell-based artificial antigen presenting cells (aAPCs) for the direct and rapid expansion of TILs isolated from primary cancer specimens. Results TILs outgrown in IL-2 undergo rapid, CD28-independent expansion in response to aAPC stimulation that requires provision of exogenous IL-2 cytokine support. aAPCs induce numerical expansion of TILs that is statistically similar to an established rapid expansion method at a 100-fold lower feeder cell to TIL ratio, and greater than those achievable using anti-CD3/CD28 activation beads or extended IL-2 culture. aAPC-expanded TILs undergo numerical expansion of tumor antigen-specific cells, remain amenable to secondary aAPC-based expansion, and have low CD4/CD8 ratios and FOXP3+ CD4+ cell frequencies. TILs can also be expanded directly from fresh enzyme-digested tumor specimens when pulsed with aAPCs. These "young" TILs are tumor-reactive, positively skewed in CD8+ lymphocyte composition, CD28 and CD27 expression, and contain fewer FOXP3+ T cells compared to parallel IL-2 cultures. Conclusion Genetically-enhanced aAPCs represent a standardized, "off-the-shelf" platform for the direct ex vivo expansion of TILs of suitable number, phenotype and function for use in adoptive immunotherapy.

Published
2011
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249. Decade-long leukaemia remissions with persistence of CD4+CAR T cells

Author

Melenhorst, J. Joseph, Chen, Gregory M., Wang, Meng, Porter, David L., Chen, Changya, Collins, McKensie A., Gao, Peng, Bandyopadhyay, Shovik, Sun, Hongxing, Zhao, Ziran, Lundh, Stefan, Pruteanu-Malinici, Iulian, Nobles, Christopher L., Maji, Sayantan, Frey, Noelle V., Gill, Saar I., Tian, Lifeng, Kulikovskaya, Irina, Gupta, Minnal, Ambrose, David E., Davis, Megan M., Fraietta, Joseph A., Brogdon, Jennifer L., Young, Regina M., Chew, Anne, Levine, Bruce L., Siegel, Donald L., Alanio, Cécile, Wherry, E. John, Bushman, Frederic D., Lacey, Simon F., Tan, Kai, and June, Carl H.

Abstract

The adoptive transfer of T lymphocytes reprogrammed to target tumour cells has demonstrated potential for treatment of various cancers1–7. However, little is known about the long-term potential and clonal stability of the infused cells. Here we studied long-lasting CD19-redirected chimeric antigen receptor (CAR) T cells in two patients with chronic lymphocytic leukaemia1–4who achieved a complete remission in 2010. CAR T cells remained detectable more than ten years after infusion, with sustained remission in both patients. Notably, a highly activated CD4+population emerged in both patients, dominating the CAR T cell population at the later time points. This transition was reflected in the stabilization of the clonal make-up of CAR T cells with a repertoire dominated by a small number of clones. Single-cell profiling demonstrated that these long-persisting CD4+CAR T cells exhibited cytotoxic characteristics along with ongoing functional activation and proliferation. In addition, longitudinal profiling revealed a population of gamma delta CAR T cells that prominently expanded in one patient concomitant with CD8+CAR T cells during the initial response phase. Our identification and characterization of these unexpected CAR T cell populations provide novel insight into the CAR T cell characteristics associated with anti-cancer response and long-term remission in leukaemia.

Published
2022
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250. Suicide, Indian Farmers, Indigenous North Americans . . . and the Shame of Shrinks.

Author

LEVINE, BRUCE E.

Abstract

JANUARY 14, 2022 Roland Chrisjohn, lead author of Dying to Please You: Indigenous Suicide in Contemporary Canada, more effectively than anyone I know, confronts this tragic denial by mental health professionals: through their medicalizing and diseasing of sociopolitically-fueled suicidality, they are enabling suffering and increasing suicide. The farmer who is distressed on account of debts and anti-farmer agricultural policies is diagnosed with depression "without delving into the toxic and chronic stress that the farmer encounters daily." Kottai is exasperated by his fellow mental health professionals, noting, "Farmers are labelled, responsibilized for their "depression" and "anxiety" exhorting them to change and adapt to unjust statutes instituted by the state.". [Extracted from the article]

Published
2022

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