LIVIVO - Search results -

Search results

Result 1 - 10 of total 25

Search options

Article ; Online: A Phase 2 Study of In Situ Oncolytic Virus Therapy and Stereotactic Body Radiation Therapy Followed by Pembrolizumab in Metastatic Non-Small Cell Lung Cancer.

Guan, Jian / Sun, Kai / Guerrero, Carlo A / Zheng, Junjun / Xu, Yitian / Mathur, Sunil / Teh, Bin S / Farach, Andrew / Zhang, Jun / Butler, Edward / Pan, Ping-Ying / Zsigmond, Eva / Mei, Zhuyong / Mejia, Jaime / Chen, Shu Hsia / Chang, Jenny C / Bernicker, Eric H

International journal of radiation oncology, biology, physics

2023 Volume 118, Issue 5, Page(s) 1531–1540

Abstract: Purpose: A phase 2 study of stereotactic body radiation therapy (SBRT) and in situ oncolytic virus therapy in metastatic non-small cell lung cancer (mNSCLC) followed by pembrolizumab (STOMP) was designed to explore the dual approach in enhancing single ... ...

Abstract	Purpose: A phase 2 study of stereotactic body radiation therapy (SBRT) and in situ oncolytic virus therapy in metastatic non-small cell lung cancer (mNSCLC) followed by pembrolizumab (STOMP) was designed to explore the dual approach in enhancing single pembrolizumab with ADV/HSV-tk plus valacyclovir gene therapy and SBRT in mNSCLC. Methods and materials: STOMP is a single-arm, open-label phase 2 study. Patients with mNSCLC received intratumoral injections of ADV/HSV-tk (5 × 10 Results: 28 patients were enrolled, of whom 27 were evaluated for response. The ORR was 33.3%, including 2 CR (7.4%) and 7 PR (25.9%). CBR was 70.4%. Six of eight (75.0%) patients who were immune checkpoint inhibitor (ICI) refractory derived clinical benefits. Responders had durable responses with median PFS, and OS not reached. The entire cohort had a median PFS of 7.4 months (95% CI, 5.1-9.6 months), and median OS of 18.1 months (95% CI, 15.4-20.9 months). The combination was well tolerated, with grade 3 or higher toxicity in 6 (21.4%) patients. Conclusions: The dual approach of in situ ADV/HSV-tk plus valacyclovir gene therapy and SBRT as a chemotherapy-sparing strategy to enhance the antitumor effect of pembrolizumab is a well-tolerated encouraging treatment in patients with mNSCLC.
MeSH term(s)	Humans ; Carcinoma, Non-Small-Cell Lung ; Lung Neoplasms ; Radiosurgery/adverse effects ; Oncolytic Virotherapy/adverse effects ; Valacyclovir/therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Antibodies, Monoclonal, Humanized
Chemical Substances	pembrolizumab (DPT0O3T46P) ; Valacyclovir (MZ1IW7Q79D) ; Antibodies, Monoclonal, Humanized
Language	English
Publishing date	2023-08-24
Publishing country	United States
Document type	Clinical Trial, Phase II ; Journal Article
ZDB-ID	197614-x
ISSN	1879-355X ; 0360-3016
ISSN (online)	1879-355X
ISSN	0360-3016
DOI	10.1016/j.ijrobp.2023.08.044
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Cologne/Königswinter

Zs.A 1218: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

Details ▾

Article ; Online: Environmental oxygen affects ex vivo growth and proliferation of mesenchymal progenitors by modulating mitogen-activated protein kinase and mammalian target of rapamycin signaling.

da Graça Cabreira, Maria / Wang, Xiaohong / Critsinelis, Andre / Setegne, Mekedlawit / Lotfi, Parisa / Wan, Ying-Wooi / Barrios, Gabriela / Mei, Zhuyong / Gee, Adrian P / Buja, Louis Maximilian / Perin, Emerson

Cytotherapy

2022 Volume 24, Issue 12, Page(s) 1201–1210

Abstract: Background aims: Stem and progenitor cells of hematopoietic and mesenchymal lineages reside in the bone marrow under low oxygen (O: Methods: Using cell-based assays and transcriptome and proteome data, the authors compared MSC cultures simultaneously ...

Abstract	Background aims: Stem and progenitor cells of hematopoietic and mesenchymal lineages reside in the bone marrow under low oxygen (O Methods: Using cell-based assays and transcriptome and proteome data, the authors compared MSC cultures simultaneously grown under a conventional 19.95% O Results: In 5% O Conclusions: Based on the potential benefits for the growth and metabolism of MSCs, the authors propose the use of 5% O
MeSH term(s)	Oxygen/metabolism ; Cells, Cultured ; Mitogen-Activated Protein Kinases ; Sirolimus ; Cell Proliferation ; Cell Differentiation/physiology ; TOR Serine-Threonine Kinases
Chemical Substances	Oxygen (S88TT14065) ; Mitogen-Activated Protein Kinases (EC 2.7.11.24) ; Sirolimus (W36ZG6FT64) ; TOR Serine-Threonine Kinases (EC 2.7.11.1)
Language	English
Publishing date	2022-09-13
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2039821-9
ISSN	1477-2566 ; 1465-3249
ISSN (online)	1477-2566
ISSN	1465-3249
DOI	10.1016/j.jcyt.2022.06.005
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Cologne/Königswinter

Zs.A 5601: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (2.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾

Article ; Online: Antitumor efficacy and safety of unedited autologous CD5.CAR T cells in relapsed/refractory mature T-cell lymphomas.

Blood

2023 Volume 143, Issue 13, Page(s) 1231–1241

Abstract: Abstract: Despite newer targeted therapies, patients with primary refractory or relapsed (r/r) T-cell lymphoma have a poor prognosis. The development of chimeric antigen receptor (CAR) T-cell platforms to treat T-cell malignancies often requires ... ...

Abstract	Abstract: Despite newer targeted therapies, patients with primary refractory or relapsed (r/r) T-cell lymphoma have a poor prognosis. The development of chimeric antigen receptor (CAR) T-cell platforms to treat T-cell malignancies often requires additional gene modifications to overcome fratricide because of shared T-cell antigens on normal and malignant T cells. We developed a CD5-directed CAR that produces minimal fratricide by downmodulating CD5 protein levels in transduced T cells while retaining strong cytotoxicity against CD5+ malignant cells. In our first-in-human phase 1 study (NCT0308190), second-generation autologous CD5.CAR T cells were manufactured from patients with r/r T-cell malignancies. Here, we report safety and efficacy data from a cohort of patients with mature T-cell lymphoma (TCL). Among the 17 patients with TCL enrolled, CD5 CAR T cells were successfully manufactured for 13 out of 14 attempted lines (93%) and administered to 9 (69%) patients. The overall response rate (complete remission or partial response) was 44%, with complete responses observed in 2 patients. The most common grade 3 or higher adverse events were cytopenias. No grade 3 or higher cytokine release syndrome or neurologic events occurred. Two patients died during the immediate toxicity evaluation period due to rapidly progressive disease. These results demonstrated that CD5.CAR T cells are safe and can induce clinical responses in patients with r/r CD5-expressing TCLs without eliminating endogenous T cells or increasing infectious complications. More patients and longer follow-up are needed for validation. This trial was registered at www.clinicaltrials.gov as #NCT0308190.
MeSH term(s)	Humans ; Immunotherapy, Adoptive/adverse effects ; Immunotherapy, Adoptive/methods ; Neoplasm Recurrence, Local/drug therapy ; T-Lymphocytes ; Chronic Disease ; Lymphoma, T-Cell/drug therapy ; Antigens, CD19
Chemical Substances	Antigens, CD19
Language	English
Publishing date	2023-12-25
Publishing country	United States
Document type	Journal Article
ZDB-ID	80069-7
ISSN	1528-0020 ; 0006-4971
ISSN (online)	1528-0020
ISSN	0006-4971
DOI	10.1182/blood.2023022204
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Uh III Zs.140: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG)
Zs.MO 364: Show issues

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article: Interleukin-15-armored GPC3-CAR T cells for patients with solid cancers.

Steffin, David / Ghatwai, Nisha / Montalbano, Antonino / Rathi, Purva / Courtney, Amy N / Arnett, Azlann B / Fleurence, Julien / Sweidan, Ramy / Wang, Thao / Zhang, Huimin / Masand, Prakash / Maris, John M / Martinez, Daniel / Pogoriler, Jennifer / Varadarajan, Navin / Thakkar, Sachin G / Lyon, Deborah / Lapteva, Natasha / Mei, Zhuyong /

Patel, Kalyani / Lopez-Terrada, Dolores / Ramos, Carlos / Lulla, Premal / Armaghany, Tannaz / Grilley, Bambi J / Dotti, Gianpietro / Metelitsa, Leonid S / Heslop, Helen E / Brenner, Malcolm K / Sumazin, Pavel / Heczey, Andras

Research square

2024

Abstract: Interleukin-15 (IL15) promotes the survival of T lymphocytes and enhances the antitumor properties of CAR T cells in preclinical models of solid neoplasms in which CAR T cells have limited ... ...

Abstract	Interleukin-15 (IL15) promotes the survival of T lymphocytes and enhances the antitumor properties of CAR T cells in preclinical models of solid neoplasms in which CAR T cells have limited efficacy
Language	English
Publishing date	2024-04-03
Publishing country	United States
Document type	Preprint
DOI	10.21203/rs.3.rs-4103623/v1
Database	MEDical Literature Analysis and Retrieval System OnLINE

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Details ▾

Article ; Online: A Phase 2 Trial of Enhancing Immune Checkpoint Blockade by Stereotactic Radiation and In Situ Virus Gene Therapy in Metastatic Triple-Negative Breast Cancer.

Sun, Kai / Xu, Yitian / Zhang, Licheng / Niravath, Polly / Darcourt, Jorge / Patel, Tejal / Teh, Bin S / Farach, Andrew M / Guerrero, Carlo / Mathur, Sunil / Sultenfuss, Mark A / Gupta, Nakul / Schwartz, Mary R / Haley, Susan L / Nair, Sindhu / Li, Xiaoxian / Nguyen, Thi Truc Anh / Butner, Joseph D / Ensor, Joe /

Mejia, Jaime A / Mei, Zhuyong / Butler, E Brian / Chen, Shu-Hsia / Bernicker, Eric H / Chang, Jenny C

Clinical cancer research : an official journal of the American Association for Cancer Research

2022 Volume 28, Issue 20, Page(s) 4392–4401

Abstract: Purpose: A Phase 2 trial of stereotactic radiotherapy and in situ cytotoxic virus therapy in patients with metastatic triple-negative breast cancer (mTNBC) followed by pembrolizumab (STOMP) was designed to evaluate dual approach of enhancing single- ... ...

Abstract	Purpose: A Phase 2 trial of stereotactic radiotherapy and in situ cytotoxic virus therapy in patients with metastatic triple-negative breast cancer (mTNBC) followed by pembrolizumab (STOMP) was designed to evaluate dual approach of enhancing single-agent immune checkpoint blockade with adenovirus-mediated expression of herpes-simplex-virus thymidine-kinase (ADV/HSV-tk) plus valacyclovir gene therapy and stereotactic body radiotherapy (SBRT) in patients with mTNBC. Patients and methods: In this single-arm, open-label Phase 2 trial, patients with mTNBC were treated with ADV/HSV-tk [5 × 1011 virus particles (vp)] intratumoral injection, followed by SBRT to the injected tumor site, then pembrolizumab (200 mg, every 3 weeks). The primary endpoint was clinical benefit rate [CBR; complete response (CR), partial response (PR), or stable disease (SD) ≥ 24 weeks per RECIST version1.1 at non-irradiated site]. Secondary endpoints included duration on treatment (DoT), overall survival (OS), and safety. Exploratory endpoints included immune response to treatment assessed by correlative tissue and blood-based biomarkers. Results: Twenty-eight patients were enrolled and treated. CBR was seen in 6 patients (21.4%), including 2 CR (7.1%), 1 PR (3.6%), and 3 SD (10.7%). Patients with clinical benefit had durable responses, with median DoT of 9.6 months and OS of 14.7 months. The median OS was 6.6 months in the total population. The combination was well tolerated. Correlative studies with Cytometry by Time of Flight (CyTOF) and imaging mass cytometry (IMC) revealed a significant increase of CD8 T cells in responders and of myeloid cells in non-responders. Conclusions: The median OS increased by more than 2-fold in patients with clinical benefit. The therapy is a well-tolerated treatment in heavily pretreated patients with mTNBC. Early detection of increased effector and effector memory CD8 T cells and myeloids correlate with response and non-response, respectively.
MeSH term(s)	Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Genetic Therapy ; Humans ; Immune Checkpoint Inhibitors ; Radiosurgery ; Thymidine/therapeutic use ; Thymidine Kinase/genetics ; Triple Negative Breast Neoplasms/drug therapy ; Triple Negative Breast Neoplasms/genetics ; Valacyclovir/therapeutic use
Chemical Substances	Immune Checkpoint Inhibitors ; Thymidine Kinase (EC 2.7.1.21) ; Valacyclovir (MZ1IW7Q79D) ; Thymidine (VC2W18DGKR)
Language	English
Publishing date	2022-07-25
Publishing country	United States
Document type	Clinical Trial, Phase II ; Journal Article
ZDB-ID	1225457-5
ISSN	1557-3265 ; 1078-0432
ISSN (online)	1557-3265
ISSN	1078-0432
DOI	10.1158/1078-0432.CCR-22-0622
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 4223: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (2.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article: T Cell-Activating Mesenchymal Stem Cells as a Biotherapeutic for HCC.

Szoor, Arpad / Vaidya, Abishek / Velasquez, Mireya Paulina / Mei, Zhuyong / Galvan, Daniel L / Torres, David / Gee, Adrian / Heczey, Andras / Gottschalk, Stephen

Molecular therapy oncolytics

2017 Volume 6, Page(s) 69–79

Abstract: The outcome for advanced stage hepatocellular carcinoma (HCC) remains poor, highlighting the need for novel therapies. Genetically modified mesenchymal stem cells (MSCs) are actively being explored as cancer therapeutics due to their inherent ability to ... ...

Abstract	The outcome for advanced stage hepatocellular carcinoma (HCC) remains poor, highlighting the need for novel therapies. Genetically modified mesenchymal stem cells (MSCs) are actively being explored as cancer therapeutics due to their inherent ability to migrate to tumor sites. We reasoned that MSCs can be genetically modified to redirect T cells to Glypican-3 (GPC3)
Language	English
Publishing date	2017-07-28
Publishing country	United States
Document type	Journal Article
ISSN	2372-7705
ISSN	2372-7705
DOI	10.1016/j.omto.2017.07.002
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article ; Online: Mesenchymal stromal cell secretomes are modulated by suspension time, delivery vehicle, passage through catheter, and exposure to adjuvants.

Parsha, Kaushik / Mir, Osman / Satani, Nikunj / Yang, Bing / Guerrero, Waldo / Mei, Zhuyong / Cai, Chunyan / Chen, Peng R / Gee, Adrian / Hanley, Patrick J / Aronowski, Jaroslaw / Savitz, Sean I

Cytotherapy

2017 Volume 19, Issue 1, Page(s) 36–46

Abstract: Background aims: Extensive animal data indicate that mesenchymal stromal cells (MSCs) improve outcome in stroke models. Intra-arterial (IA) injection is a promising route of delivery for MSCs. Therapeutic effect of MSCs in stroke is likely based on the ... ...

Abstract	Background aims: Extensive animal data indicate that mesenchymal stromal cells (MSCs) improve outcome in stroke models. Intra-arterial (IA) injection is a promising route of delivery for MSCs. Therapeutic effect of MSCs in stroke is likely based on the broad repertoire of secreted trophic and immunomodulatory cytokines produced by MSCs. We determined the differential effects of exposing MSCs to different types of clinically relevant vehicles, and/or different additives and passage through a catheter relevant to IA injections. Methods: MSCs derived from human bone marrow were tested in the following vehicles: 5% albumin (ALB), 6% Hextend (HEX) and 40% dextran (DEX). Each solution was tested (i) alone, (ii) with low-dose heparin, (iii) with 10% Omnipaque, or (iv) a combination of heparin and Omnipaque. Cells in vehicles were collected directly or passed through an IA catheter, and MSC viability and cytokine release profiles were assessed. Results: Cell viability remained above 90% under all tested conditions with albumin being the highest at 97%. Viability was slightly reduced after catheter passage or exposure to heparin or Omnipaque. Catheter passage had little effect on MSC cytokine secretion. ALB led to increased release of angiogenic factors such as vascular endothelial growth factor compared with other vehicles, while HEX and DEX led to suppression of pro-inflammatory cytokines such as interleukin-6. However, when these three vehicles were subjected to catheter passage and/or exposure to additives, the cytokine release profile varied depending on the combination of conditions to which MSCs were exposed. Discussion: Exposure of MSCs to certain types of vehicles or additives changes the profile of cytokine secretion. The activation phenotype of MSCs may therefore be affected by the vehicles used for these cells or the exposure to the adjuvants used in their administration.
Language	English
Publishing date	2017-01
Publishing country	England
Document type	Journal Article
ZDB-ID	2039821-9
ISSN	1477-2566 ; 1465-3249
ISSN (online)	1477-2566
ISSN	1465-3249
DOI	10.1016/j.jcyt.2016.10.006
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Cologne/Königswinter

Zs.A 5601: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (2.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾

Article ; Online: Clinical and immunological responses after CD30-specific chimeric antigen receptor-redirected lymphocytes.

Ramos, Carlos A / Ballard, Brandon / Zhang, Huimin / Dakhova, Olga / Gee, Adrian P / Mei, Zhuyong / Bilgi, Mrinalini / Wu, Meng-Fen / Liu, Hao / Grilley, Bambi / Bollard, Catherine M / Chang, Bill H / Rooney, Cliona M / Brenner, Malcolm K / Heslop, Helen E / Dotti, Gianpietro / Savoldo, Barbara

The Journal of clinical investigation

2017 Volume 127, Issue 9, Page(s) 3462–3471

Abstract: Background: Targeting CD30 with monoclonal antibodies in Hodgkin lymphoma (HL) and anaplastic large cell lymphoma (ALCL) has had profound clinical success. However, adverse events, mainly mediated by the toxin component of the conjugated antibodies, ... ...

Abstract	Background: Targeting CD30 with monoclonal antibodies in Hodgkin lymphoma (HL) and anaplastic large cell lymphoma (ALCL) has had profound clinical success. However, adverse events, mainly mediated by the toxin component of the conjugated antibodies, cause treatment discontinuation in many patients. Targeting CD30 with T cells expressing a CD30-specific chimeric antigen receptor (CAR) may reduce the side effects and augment antitumor activity. Methods: We conducted a phase I dose escalation study in which 9 patients with relapsed/refractory HL or ALCL were infused with autologous T cells that were gene-modified with a retroviral vector to express the CD30-specific CAR (CD30.CAR-Ts) encoding the CD28 costimulatory endodomain. Three dose levels, from 0.2 × 108 to 2 × 108 CD30.CAR-Ts/m2, were infused without a conditioning regimen. All other therapy for malignancy was discontinued at least 4 weeks before CD30.CAR-T infusion. Seven patients had previously experienced disease progression while being treated with brentuximab. Results: No toxicities attributable to CD30.CAR-Ts were observed. Of 7 patients with relapsed HL, 1 entered complete response (CR) lasting more than 2.5 years after the second infusion of CD30.CAR-Ts, 1 remained in continued CR for almost 2 years, and 3 had transient stable disease. Of 2 patients with ALCL, 1 had a CR that persisted 9 months after the fourth infusion of CD30.CAR-Ts. CD30.CAR-T expansion in peripheral blood peaked 1 week after infusion, and CD30.CAR-Ts remained detectable for over 6 weeks. Although CD30 may also be expressed by normal activated T cells, no patients developed impaired virus-specific immunity. Conclusion: CD30.CAR-Ts are safe and can lead to clinical responses in patients with HL and ALCL, indicating that further assessment of this therapy is warranted. Trial registration: ClinicalTrials.gov NCT01316146. Funding: National Cancer Institute (3P50CA126752, R01CA131027 and P30CA125123), National Heart, Lung, and Blood Institute (R01HL114564), and Leukemia and Lymphoma Society (LLSTR 6227-08).
MeSH term(s)	Adult ; Antineoplastic Agents/chemistry ; CD28 Antigens/chemistry ; Disease Progression ; Dose-Response Relationship, Drug ; Female ; Hodgkin Disease/immunology ; Hodgkin Disease/therapy ; Humans ; Immunoconjugates/administration & dosage ; Immunoconjugates/therapeutic use ; Immunophenotyping ; Ki-1 Antigen/metabolism ; Lymphoma, Large-Cell, Anaplastic/immunology ; Lymphoma, Large-Cell, Anaplastic/therapy ; Male ; Middle Aged ; Molecular Targeted Therapy ; Neoplasm Recurrence, Local ; Receptors, Antigen, T-Cell/chemistry ; T-Lymphocytes/cytology ; Transplantation Conditioning ; Treatment Outcome ; Young Adult
Chemical Substances	Antineoplastic Agents ; CD28 Antigens ; Immunoconjugates ; Ki-1 Antigen ; Receptors, Antigen, T-Cell ; brentuximab vedotin (7XL5ISS668)
Language	English
Publishing date	2017-08-14
Publishing country	United States
Document type	Clinical Trial, Phase I ; Journal Article
ZDB-ID	3067-3
ISSN	1558-8238 ; 0021-9738
ISSN (online)	1558-8238
ISSN	0021-9738
DOI	10.1172/JCI94306
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Ua VI Zs.184: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: CAR T Cells Administered in Combination with Lymphodepletion and PD-1 Inhibition to Patients with Neuroblastoma.

Heczey, Andras / Louis, Chrystal U / Savoldo, Barbara / Dakhova, Olga / Durett, April / Grilley, Bambi / Liu, Hao / Wu, Mengfeng F / Mei, Zhuyong / Gee, Adrian / Mehta, Birju / Zhang, Huimin / Mahmood, Nadia / Tashiro, Haruko / Heslop, Helen E / Dotti, Gianpietro / Rooney, Cliona M / Brenner, Malcolm K

Molecular therapy : the journal of the American Society of Gene Therapy

2017 Volume 25, Issue 9, Page(s) 2214–2224

Abstract: Targeting disialoganglioside (GD2) on neuroblastoma (NB) with T cells expressing a first-generation chimeric antigen receptor (CAR) was safe, but the cells had poor expansion and long-term persistence. We developed a third-generation GD2-CAR (GD2-CAR3) ... ...

Abstract	Targeting disialoganglioside (GD2) on neuroblastoma (NB) with T cells expressing a first-generation chimeric antigen receptor (CAR) was safe, but the cells had poor expansion and long-term persistence. We developed a third-generation GD2-CAR (GD2-CAR3) and hypothesized that GD2-CAR3 T cells (CARTs) would be safe and effective. This phase 1 study enrolled relapsed or refractory NB patients in three cohorts. Cohort 1 received CART alone, cohort 2 received CARTs plus cyclophosphamide and fludarabine (Cy/Flu), and cohort 3 was treated with CARTs, Cy/Flu, and a programmed death-1 (PD-1) inhibitor. Eleven patients were treated with CARTs. The infusions were safe, and no dose-limiting toxicities occurred. CARTs were detectable in cohort 1, but the lymphodepletion induced by Cy/Flu increased circulating levels of the homeostatic cytokine interleukin (IL)-15 (p = 0.003) and increased CART expansion by up to 3 logs (p = 0.03). PD-1 inhibition did not further enhance expansion or persistence. Antitumor responses at 6 weeks were modest. We observed a striking expansion of CD45/CD33/CD11b/CD163
MeSH term(s)	Adolescent ; Antineoplastic Agents, Immunological/administration & dosage ; Antineoplastic Agents, Immunological/adverse effects ; Antineoplastic Agents, Immunological/therapeutic use ; Child ; Child, Preschool ; Cohort Studies ; Combined Modality Therapy ; Cytokines/blood ; Female ; Humans ; Immunotherapy, Adoptive/adverse effects ; Immunotherapy, Adoptive/methods ; Lymphocyte Count ; Lymphocyte Depletion ; Male ; Molecular Targeted Therapy ; Myeloid Cells/metabolism ; Neuroblastoma/immunology ; Neuroblastoma/mortality ; Neuroblastoma/pathology ; Neuroblastoma/therapy ; Programmed Cell Death 1 Receptor/antagonists & inhibitors ; Receptors, Antigen, T-Cell/genetics ; Receptors, Antigen, T-Cell/metabolism ; Recombinant Fusion Proteins ; T-Lymphocytes/immunology ; T-Lymphocytes/metabolism ; Transplantation Conditioning ; Treatment Outcome ; Young Adult
Chemical Substances	Antineoplastic Agents, Immunological ; Cytokines ; PDCD1 protein, human ; Programmed Cell Death 1 Receptor ; Receptors, Antigen, T-Cell ; Recombinant Fusion Proteins
Language	English
Publishing date	2017-06-09
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2010592-7
ISSN	1525-0024 ; 1525-0016
ISSN (online)	1525-0024
ISSN	1525-0016
DOI	10.1016/j.ymthe.2017.05.012
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Cologne/Königswinter

Zs.A 5640: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (2.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾

Article ; Online: Phase 1 clinical trial of adoptive immunotherapy using "off-the-shelf" activated natural killer cells in patients with refractory and relapsed acute myeloid leukemia.

Boyiadzis, Michael / Agha, Mounzer / Redner, Robert L / Sehgal, Alison / Im, Annie / Hou, Jing-Zhou / Farah, Rafic / Dorritie, Kathleen A / Raptis, Anastasios / Lim, Seah H / Wang, Hong / Lapteva, Natalia / Mei, Zhuyong / Butterfield, Lisa H / Rooney, Cliona M / Whiteside, Theresa L

Cytotherapy

2017 Volume 19, Issue 10, Page(s) 1225–1232

Abstract: Background aims: Activated NK cells (aNK) generated by expansion of a human interleukin-2-dependent NK cell line (NK-92) were shown to mediate strong anti-leukemia activity. This phase 1 study evaluated feasibility, safety, and activity of aNK cells ... ...

Abstract	Background aims: Activated NK cells (aNK) generated by expansion of a human interleukin-2-dependent NK cell line (NK-92) were shown to mediate strong anti-leukemia activity. This phase 1 study evaluated feasibility, safety, and activity of aNK cells adoptively transferred to patients with refractory/relapsed acute myeloid leukemia (AML). In addition, effects of these aNK cells on the patient's immune system were evaluated. Methods: Two cell-dose levels (1 × 10 Results: Seven patients with refractory/relapsed AML were treated with a total of 20 aNK cell infusions. None of the 7 patients experienced dose-limiting toxicities during the aNK cell administration or during 21 days of the post-infusion observation period. No grade 3-4 toxicities (probable or definite) related to aNK cell infusions occurred. Activity was transient in 3 of 7 patients. No significant changes in the patient's lymphocyte counts, subsets frequency, phenotype or activity were observed post-infusion. Cell dose-dependent effects in the plasma levels of several cytokines were observed. Discussion: The trial demonstrated the safety and feasibility of adoptive cell therapy with "off-the-shelf" aNK cells in patients with refractory/relapsed AML. These data provide the foundation for future combination immunotherapy trials and for the optimization of aNK cell based therapies in patients with AML.
MeSH term(s)	Aged ; Aged, 80 and over ; Cell Transplantation/adverse effects ; Cell Transplantation/methods ; Cytokines/blood ; Female ; Humans ; Immunotherapy, Adoptive/adverse effects ; Immunotherapy, Adoptive/methods ; Interleukin-2/pharmacology ; Killer Cells, Natural/drug effects ; Killer Cells, Natural/immunology ; Killer Cells, Natural/transplantation ; Leukemia, Myeloid, Acute/pathology ; Leukemia, Myeloid, Acute/therapy ; Male ; Middle Aged ; Treatment Outcome
Chemical Substances	Cytokines ; Interleukin-2
Language	English
Publishing date	2017-08-30
Publishing country	England
Document type	Clinical Trial, Phase I ; Journal Article
ZDB-ID	2039821-9
ISSN	1477-2566 ; 1465-3249
ISSN (online)	1477-2566
ISSN	1465-3249
DOI	10.1016/j.jcyt.2017.07.008
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Cologne/Königswinter

Zs.A 5601: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (2.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾

To top

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Inter-library loan at ZB MED

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito

Inter-library loan at ZB MED

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito