LIVIVO - Search results -

Search results

Result 1 - 10 of total 15

Search options

Article ; Online: Efficacy, safety, and biomarker analyses of bintrafusp alfa, a bifunctional fusion protein targeting TGF-β and PD-L1, in patients with advanced non-small cell lung cancer.

Rajan, Arun / Abdul Sater, Houssein / Rahma, Osama / Agajanian, Richy / Lassoued, Wiem / Marté, Jennifer L / Tsai, Yo-Ting / Donahue, Renee N / Lamping, Elizabeth / Bailey, Shania / Weisman, Andrew / Walter-Rodriguez, Beatriz / Ito, Rena / Vugmeyster, Yulia / Sato, Masashi / Machl, Andreas / Schlom, Jeffrey / Gulley, James L

Journal for immunotherapy of cancer

2024 Volume 12, Issue 3

Abstract: Background: Bintrafusp alfa, a first-in-class bifunctional fusion protein targeting transforming growth factor-β (TGF-β) and programmed cell death ligand 1, has demonstrated encouraging efficacy as second-line treatment in patients with non-small cell ... ...

Abstract	Background: Bintrafusp alfa, a first-in-class bifunctional fusion protein targeting transforming growth factor-β (TGF-β) and programmed cell death ligand 1, has demonstrated encouraging efficacy as second-line treatment in patients with non-small cell lung cancer (NSCLC) in a dose expansion cohort of the phase 1, open-label clinical trial (NCT02517398). Here, we report the safety, efficacy, and biomarker analysis of bintrafusp alfa in a second expansion cohort of the same trial (biomarker cohort). Methods: Patients with stage IIIb/IV NSCLC who were either immune checkpoint inhibitor (ICI)-naïve (n=18) or ICI-experienced (n=23) were enrolled. The primary endpoint was the best overall response. Paired biopsies (n=9/41) and peripheral blood (n=14/41) pretreatment and on-treatment were studied to determine the immunological effects of treatment and for associations with clinical activity. Results: Per independent review committee assessment, objective responses were observed in the ICI-naïve group (overall response rate, 27.8%). No new or unexpected safety signals were identified. Circulating TGF-β levels were reduced (>97%; p<0.001) 2 weeks after initiation of treatment with bintrafusp alfa and remained reduced up to 12 weeks. Increases in lymphocytes and tumor-associated macrophages (TAMs) were observed in on-treatment biospies, with an increase in the M2 (tumor trophic TAMs)/M1 (inflammatory TAMs) ratio associated with poor outcomes. Specific peripheral immune analytes at baseline and early changes after treatment were associated with clinical response. Conclusions: Bintrafusp alfa was observed to have modest clinical activity and manageable safety, and was associated with notable immunologic changes involving modulation of the tumor immune microenvironment in patients with advanced NSCLC.
MeSH term(s)	Humans ; Carcinoma, Non-Small-Cell Lung/pathology ; Lung Neoplasms/pathology ; B7-H1 Antigen ; Immunologic Factors/therapeutic use ; Immunotherapy ; Tumor Microenvironment
Chemical Substances	B7-H1 Antigen ; Immunologic Factors
Language	English
Publishing date	2024-03-13
Publishing country	England
Document type	Clinical Trial, Phase I ; Journal Article
ZDB-ID	2719863-7
ISSN	2051-1426 ; 2051-1426
ISSN (online)	2051-1426
ISSN	2051-1426
DOI	10.1136/jitc-2023-008480
Database	MEDical Literature Analysis and Retrieval System OnLINE

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.

Article ; Online: Validity of 1% Hormonal Receptor Positivity Cutoff by the ASCO/College of American Pathologists Guidelines at the Georgia Cancer Center.

Kreidieh, Firas / Sadek, Ramses F / Zhang, Li Fang / Gopal, Aaron / Blaize, Jean-Pierre / Yashar, David / Patel, Reena / Patel, Hiral S / Tang, Shou-Ching / Abdul Sater, Houssein

JCO precision oncology

2022 Volume 6, Page(s) e2100201

Abstract: Purpose: Treatment of breast cancer (BC) with borderline or low (1%-9%) estrogen and progesterone expression remains controversial, with recent data disputing ASCO/College of American Pathologists 2010 guidelines that lowered the threshold of receptor ... ...

Abstract	Purpose: Treatment of breast cancer (BC) with borderline or low (1%-9%) estrogen and progesterone expression remains controversial, with recent data disputing ASCO/College of American Pathologists 2010 guidelines that lowered the threshold of receptor positivity from 10% to 1%. The objective of this retrospective study was to validate these guidelines at the Georgia Cancer Center with a high percentage of Black race. Methods: All female patients with invasive BC diagnosed between 2005 and 2010 at the Georgia Cancer Center were chart reviewed up to an 11-year follow-up with data cutoff at 2016. We used Cox regression to explore survival among three hormonal status (HS) groups (< 1%, 1%-9%, and ≥ 10%) adjusting for all known BC clinicopathologic variables. Fisher's exact test was used to evaluate response to endocrine therapy (ET). Results: Among 431 patients with mean age 59 years, 24.75% had HS < 1%, 17.5% HS 1%-9%, and 57.75% HS ≥ 10%. Race was 43.75% Black and 54% White. Disease stages were early (I-IIIA) in 84.4% and advanced (IIIB-IV) in 15.56%. Mortality in HS < 1% was significantly higher than that in HS ≥ 10% (hazard ratio [HR]: 1.8; 95% CI, 1.07 to 3.02), whereas no significant mortality difference between HS 1%-9% and HS ≥ 10% (HR: 1.05; 95% CI, 0.48 to 2.30) was observed. ET was protective, and treated patients had higher predicted survival than untreated patients in the 1%-9% group (HR: 0.10; 95% CI, 0.01 to 0.85). There was no significant mortality difference between ET-treated HS 1%-9% and ≥ 10% groups. Conclusion: One percent cutoff predicted superior survival on treatment with ET compared with the other groups, and HS as low as 1%-9% was equiprognostic to HS ≥ 10%. Whether other factors such as lymphovascular invasion, grade, and other parameters change the behavior of the 1%-9% HS group remains to be explored.
MeSH term(s)	Breast Neoplasms/drug therapy ; Female ; Georgia/epidemiology ; Humans ; Middle Aged ; Pathologists ; Proportional Hazards Models ; Retrospective Studies
Language	English
Publishing date	2022-02-24
Publishing country	United States
Document type	Journal Article
ISSN	2473-4284
ISSN (online)	2473-4284
DOI	10.1200/PO.21.00201
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: Dual PD-L1 and TGF-b blockade in patients with recurrent respiratory papillomatosis.

Robbins, Yvette / Friedman, Jay / Clavijo, Paul E / Sievers, Cem / Bai, Ke / Donahue, Renee N / Schlom, Jeffrey / Sinkoe, Andrew / Hinrichs, Christian S / Allen, Clint / Abdul Sater, Houssein / Gulley, James L / Norberg, Scott

Journal for immunotherapy of cancer

2021 Volume 9, Issue 8

Abstract: Background: Recurrent respiratory papillomatosis (RRP) is a human papillomavirus (HPV) driven neoplastic disorder of the upper aerodigestive tract that causes significant morbidity and can lead to fatal airway obstruction. Prior clinical study ... ...

Abstract	Background: Recurrent respiratory papillomatosis (RRP) is a human papillomavirus (HPV) driven neoplastic disorder of the upper aerodigestive tract that causes significant morbidity and can lead to fatal airway obstruction. Prior clinical study demonstrated clinical benefit with the programmed death-ligand 1 (PD-L1) monoclonal antibody avelumab. Bintrafusp alpha is a bifunctional inhibitor of PD-L1 and transforming growth factor-beta (TGF-b) that has shown clinical activity in several cancer types. Methods: We conducted a phase II clinical trial evaluating bintrafusp alpha in adults with RRP. Papilloma samples before and after treatment with bintrafusp alpha were assessed for correlates of response with multiplex immunofluorescence as well as immunological and genomic analyses. Post hoc analyses of papilloma samples before and after treatment with avelumab were assessed for comparison. Results: Dual PD-L1/TGF-b inhibition failed to abrogate papilloma growth in most subjects and increased the frequency of clinically indicated interventions after treatment in four of eight subjects based on each subject's own historical control. TGF-b neutralization consistently decreased pSMAD3 and p21 and increased Ki67 expression within the basal layers of papillomas, indicating that TGF-b restrained proliferation. These alterations were not observed in papillomas treated with PD-L1 blockade alone. Dual PD-L1/TGF-b inhibition did not enhance anti-HPV immunity within papillomas beyond that observed with PD-L1 blockade. Genomic alterations in TGF-b superfamily genes were infrequent in papillomas and normal mucosa but present in a significant fraction of head and neck carcinomas. Conclusions: Intact TGF-b signaling restrains proliferation within papillomas, and the use of clinical agents that abrogate this pathway should be avoided in patients with RRP. Trial registration numbers: NCT03707587 and NCT02859454.
MeSH term(s)	Animals ; Antibodies, Monoclonal/therapeutic use ; Antibodies, Monoclonal, Humanized/therapeutic use ; Female ; Humans ; Immune Checkpoint Inhibitors/therapeutic use ; Immunologic Factors/therapeutic use ; Immunotherapy/methods ; Mice ; NIH 3T3 Cells ; Papilloma/drug therapy ; Papillomavirus Infections/drug therapy ; Respiratory Tract Infections/drug therapy ; Transforming Growth Factor beta/antagonists & inhibitors ; Tumor Microenvironment/immunology
Chemical Substances	Antibodies, Monoclonal ; Antibodies, Monoclonal, Humanized ; Immune Checkpoint Inhibitors ; Immunologic Factors ; Transforming Growth Factor beta ; avelumab (KXG2PJ551I)
Language	English
Publishing date	2021-08-30
Publishing country	England
Document type	Clinical Trial, Phase II ; Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2719863-7
ISSN	2051-1426 ; 2051-1426
ISSN (online)	2051-1426
ISSN	2051-1426
DOI	10.1136/jitc-2021-003113
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Combining a β3 adrenergic receptor agonist with alpha-lipoic acid reduces inflammation in male mice with diet-induced obesity.

Abdul Sater, Zahraa / Cero, Cheryl / Pierce, Anne E / Lea, Hannah J / Abdul Sater, Houssein / Zhu, Kenneth Y / Liu, Naili / Ma, Yinyan / Gavrilova, Oksana / Cypess, Aaron M

Obesity (Silver Spring, Md.)

2021 Volume 30, Issue 1, Page(s) 153–164

Abstract: Objectives: Beta-3 adrenergic receptors (β3-AR) stimulate lipolysis and thermogenesis in white and brown adipose tissue (WAT and BAT). Obesity increases oxidative stress and inflammation that attenuate AT β3-AR signaling. The objective of this study was ...

Abstract	Objectives: Beta-3 adrenergic receptors (β3-AR) stimulate lipolysis and thermogenesis in white and brown adipose tissue (WAT and BAT). Obesity increases oxidative stress and inflammation that attenuate AT β3-AR signaling. The objective of this study was to test the hypothesis that the combination of the β3-AR agonist CL-316,243 (CL) and the antioxidant alpha-lipoic acid (ALA) would lower inflammation in diet-induced obesity (DIO) and improve β3-AR function. Methods: A total of 40 DIO mice were separated into four groups: Control (per os and intraperitoneal [IP] vehicle); CL alone (0.01 mg/kg IP daily); ALA alone (250 mg/kg in drinking water); or ALA+CL combination, all for 5 weeks. Results: Food intake was similar in all groups; however, mice receiving ALA+CL showed improved body composition and inflammation as well as lower body weight (+1.7 g Control vs. -2.5 g ALA+CL [-7%]; p < 0.01) and percentage of body fat (-9%, p < 0.001). Systemic and epididymal WAT inflammation was lower with ALA+CL than all other groups, with enhanced recruitment of epididymal WAT anti-inflammatory CD206+ M2 macrophages. β3-AR signaling in WAT was enhanced in the combination-treatment group, with higher mRNA and protein levels of thermogenic uncoupling protein 1 and AT lipases. Conclusions: Chronic treatment with ALA and a β3-AR agonist reduces DIO-induced inflammation. AT immune modulation could be a therapeutic target in patients with obesity.
MeSH term(s)	Adipose Tissue, Brown/metabolism ; Adrenergic Agonists/metabolism ; Adrenergic Agonists/pharmacology ; Animals ; Diet, High-Fat/adverse effects ; Humans ; Inflammation/drug therapy ; Inflammation/metabolism ; Male ; Mice ; Mice, Obese ; Obesity/drug therapy ; Obesity/metabolism ; Thioctic Acid/metabolism ; Thioctic Acid/pharmacology ; Thioctic Acid/therapeutic use
Chemical Substances	Adrenergic Agonists ; Thioctic Acid (73Y7P0K73Y)
Language	English
Publishing date	2021-11-25
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Intramural
ZDB-ID	2230457-5
ISSN	1930-739X ; 1071-7323 ; 1930-7381
ISSN (online)	1930-739X
ISSN	1071-7323 ; 1930-7381
DOI	10.1002/oby.23309
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 4061: 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)
Zs.MG 87: Show issues

Order via subito

Details ▾

Article ; Online: Therapy of Established Tumors with Rationally Designed Multiple Agents Targeting Diverse Immune-Tumor Interactions: Engage, Expand, Enable.

Fabian, Kellsye P / Malamas, Anthony S / Padget, Michelle R / Solocinski, Kristen / Wolfson, Benjamin / Fujii, Rika / Abdul Sater, Houssein / Schlom, Jeffrey / Hodge, James W

Cancer immunology research

2020 Volume 9, Issue 2, Page(s) 239–252

Abstract: Immunotherapy of immunologically cold solid tumors may require multiple agents to engage immune effector cells, expand effector populations and activities, and enable immune responses in the tumor microenvironment (TME). To target these distinct ... ...

Abstract	Immunotherapy of immunologically cold solid tumors may require multiple agents to engage immune effector cells, expand effector populations and activities, and enable immune responses in the tumor microenvironment (TME). To target these distinct phenomena, we strategically chose five clinical-stage immuno-oncology agents, namely, (i) a tumor antigen-targeting adenovirus-based vaccine (Ad-CEA) and an IL15 superagonist (N-803) to activate tumor-specific T cells, (ii) OX40 and GITR agonists to expand and enhance the activated effector populations, and (iii) an IDO inhibitor (IDOi) to enable effector-cell activity in the TME. Flow cytometry, T-cell receptor (TCR) sequencing, and RNA-sequencing (RNA-seq) analyses showed that in the CEA-transgenic murine colon carcinoma (MC38-CEA) tumor model, Ad-CEA + N-803 combination therapy resulted in immune-mediated antitumor effects and promoted the expression of costimulatory molecules on immune subsets, OX40 and GITR, and the inhibitory molecule IDO. Treatment with Ad-CEA + N-803 + OX40 + GITR + IDOi, termed the pentatherapy regimen, resulted in the greatest inhibition of tumor growth and protection from tumor rechallenge without toxicity. Monotherapy with any of the agents had little to no antitumor activity, whereas combining two, three, or four agents had minimal antitumor effects. Immune analyses demonstrated that the pentatherapy combination induced CD4
MeSH term(s)	Animals ; CD8-Positive T-Lymphocytes/immunology ; Cancer Vaccines/immunology ; Cell Line, Tumor ; Colonic Neoplasms/immunology ; Colonic Neoplasms/therapy ; Disease Models, Animal ; Female ; Humans ; Immunotherapy/methods ; Lymphocyte Activation ; Mice ; Mice, Inbred C57BL ; T-Lymphocytes, Regulatory/immunology ; Tumor Microenvironment/immunology
Chemical Substances	Cancer Vaccines
Language	English
Publishing date	2020-12-22
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Intramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2732489-8
ISSN	2326-6074 ; 2326-6066
ISSN (online)	2326-6074
ISSN	2326-6066
DOI	10.1158/2326-6066.CIR-20-0638
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 7022: 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: Phase I study of a multitargeted recombinant Ad5 PSA/MUC-1/brachyury-based immunotherapy vaccine in patients with metastatic castration-resistant prostate cancer (mCRPC).

Bilusic, Marijo / McMahon, Sheri / Madan, Ravi A / Karzai, Fatima / Tsai, Yo-Ting / Donahue, Renee N / Palena, Claudia / Jochems, Caroline / Marté, Jennifer L / Floudas, Charalampos / Strauss, Julius / Redman, Jason / Abdul Sater, Houssein / Rabizadeh, Shahrooz / Soon-Shiong, Patrick / Schlom, Jeffrey / Gulley, James L

Journal for immunotherapy of cancer

2021 Volume 9, Issue 3

Abstract: Background: Antitumor vaccines targeting tumor-associated antigens (TAAs) can generate antitumor immune response. A novel vaccine platform using adenovirus 5 (Ad5) vectors [E1-, E2b-] targeting three TAAs-prostate-specific antigen (PSA), brachyury, and ... ...

Abstract	Background: Antitumor vaccines targeting tumor-associated antigens (TAAs) can generate antitumor immune response. A novel vaccine platform using adenovirus 5 (Ad5) vectors [E1-, E2b-] targeting three TAAs-prostate-specific antigen (PSA), brachyury, and MUC-1-has been developed. Both brachyury and the C-terminus of MUC-1 are overexpressed in metastatic castration-resistant prostate cancer (mCRPC) and have been shown to play an important role in resistance to chemotherapy, epithelial-mesenchymal transition, and metastasis. The transgenes for PSA, brachyury, and MUC-1 all contain epitope modifications for the expression of CD8+ T-cell enhancer agonist epitopes. We report here the first-in-human trial of this vaccine platform. Methods: Patients with mCRPC were given concurrently three vaccines targeting PSA, brachyury, and MUC-1 at 5×10 Results: Eighteen patients with mCRPC were enrolled between July 2018 and September 2019 and received at least one vaccination. Median PSA was 25.58 ng/mL (range, 0.65-1006 ng/mL). The vaccine was tolerable and safe, and no grade >3 treatment-related adverse events or dose-limiting toxicities (DLTs) were observed. One patient had a partial response, while five patients had confirmed PSA decline and five had stable disease for >6 months. Median progression-free survival was 22 weeks (95% CI: 19.1 to 34). Seventeen (100%) of 17 patients mounted T-cell responses to at least one TAA, whereras 8 (47%) of 17 patients mounted immune responses to all three TAAs. Multifunctional T-cell responses to PSA, MUC-1, and brachyury were also detected after vaccination in the majority of the patients. Conclusions: Ad5 PSA/MUC-1/brachyury vaccine is well tolerated. The primary end points were met and there were no DLTs. The recommended phase II dose is 5×10 Trial registration number: NCT03481816.
MeSH term(s)	Adenoviridae/genetics ; Adenoviridae/immunology ; Aged ; Aged, 80 and over ; Cancer Vaccines/adverse effects ; Cancer Vaccines/genetics ; Cancer Vaccines/immunology ; Cancer Vaccines/therapeutic use ; Fetal Proteins/genetics ; Fetal Proteins/immunology ; Genetic Vectors ; Humans ; Kallikreins/genetics ; Kallikreins/immunology ; Male ; Middle Aged ; Mucin-1/genetics ; Mucin-1/immunology ; Progression-Free Survival ; Prostate-Specific Antigen/genetics ; Prostate-Specific Antigen/immunology ; Prostatic Neoplasms, Castration-Resistant/genetics ; Prostatic Neoplasms, Castration-Resistant/immunology ; Prostatic Neoplasms, Castration-Resistant/therapy ; T-Box Domain Proteins/genetics ; T-Box Domain Proteins/immunology ; Time Factors ; Vaccination ; Vaccine Efficacy ; Vaccines, Combined/adverse effects ; Vaccines, Combined/genetics ; Vaccines, Combined/immunology ; Vaccines, Combined/therapeutic use ; Viral Vaccines
Chemical Substances	Cancer Vaccines ; Fetal Proteins ; MUC1 protein, human ; Mucin-1 ; T-Box Domain Proteins ; Vaccines, Combined ; Viral Vaccines ; KLK3 protein, human (EC 3.4.21.-) ; Kallikreins (EC 3.4.21.-) ; Prostate-Specific Antigen (EC 3.4.21.77) ; Brachyury protein (EQ43SC3GDB)
Language	English
Publishing date	2021-03-24
Publishing country	England
Document type	Clinical Trial, Phase I ; Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2719863-7
ISSN	2051-1426 ; 2051-1426
ISSN (online)	2051-1426
ISSN	2051-1426
DOI	10.1136/jitc-2021-002374
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Chimeric antigen receptor engineered NK cellular immunotherapy overcomes the selection of T-cell escape variant cancer cells.

Lee, Maxwell Y / Robbins, Yvette / Sievers, Cem / Friedman, Jay / Abdul Sater, Houssein / Clavijo, Paul E / Judd, Nancy / Tsong, Edward / Silvin, Chris / Soon-Shiong, Patrick / Padget, Michelle R / Schlom, Jeffrey / Hodge, James / Hinrichs, Christian / Allen, Clint

Journal for immunotherapy of cancer

2021 Volume 9, Issue 3

Abstract: Background: As heterogeneous tumors develop in the face of intact immunity, tumor cells harboring genomic or expression defects that favor evasion from T-cell detection or elimination are selected. For patients with such tumors, T cell-based ... ...

Abstract	Background: As heterogeneous tumors develop in the face of intact immunity, tumor cells harboring genomic or expression defects that favor evasion from T-cell detection or elimination are selected. For patients with such tumors, T cell-based immunotherapy alone infrequently results in durable tumor control. Methods: Here, we developed experimental models to study mechanisms of T-cell escape and demonstrated that resistance to T-cell killing can be overcome by the addition of natural killer (NK) cells engineered to express a chimeric antigen receptor (CAR) targeting programmed death ligand-1 (PD-L1). Results: In engineered models of tumor heterogeneity, PD-L1 CAR-engineered NK cells (PD-L1 t-haNKs) prevented the clonal selection of T cell-resistant tumor cells observed with T-cell treatment alone in multiple models. Treatment of heterogenous cancer cell populations with T cells resulted in interferon gamma (IFN-γ) release and subsequent upregulation of PD-L1 on tumor cells that escaped T-cell killing through defects in antigen processing and presentation, priming escape cell populations for PD-L1 dependent killing by PD-L1 t-haNKs in vitro and in vivo. Conclusions: These results describe the underlying mechanisms governing synergistic antitumor activity between T cell-based immunotherapy that results in IFN-γ production, upregulation of PD-L1 on T-cell escape cells, and the use of PD-L1 CAR-engineered NK cells to target and eliminate resistant tumor cell populations.
MeSH term(s)	Animals ; B7-H1 Antigen/genetics ; B7-H1 Antigen/metabolism ; CRISPR-Cas Systems ; Cell Line, Tumor ; Databases, Genetic ; Gene Editing ; HLA Antigens/metabolism ; Head and Neck Neoplasms/genetics ; Head and Neck Neoplasms/immunology ; Head and Neck Neoplasms/metabolism ; Head and Neck Neoplasms/therapy ; Humans ; Immunotherapy, Adoptive ; Interferon-gamma/metabolism ; Killer Cells, Natural/immunology ; Killer Cells, Natural/metabolism ; Killer Cells, Natural/transplantation ; Lymphocyte Activation ; Lymphocytes, Tumor-Infiltrating/immunology ; Lymphocytes, Tumor-Infiltrating/metabolism ; Mice, Inbred NOD ; Mice, SCID ; Receptors, Chimeric Antigen/genetics ; Receptors, Chimeric Antigen/immunology ; Squamous Cell Carcinoma of Head and Neck/genetics ; Squamous Cell Carcinoma of Head and Neck/immunology ; Squamous Cell Carcinoma of Head and Neck/metabolism ; Squamous Cell Carcinoma of Head and Neck/therapy ; T-Lymphocytes/immunology ; T-Lymphocytes/metabolism ; T-Lymphocytes/transplantation ; Tumor Burden ; Tumor Escape ; Tumor Microenvironment ; Xenograft Model Antitumor Assays ; Mice
Chemical Substances	B7-H1 Antigen ; CD274 protein, human ; HLA Antigens ; IFNG protein, human ; Receptors, Chimeric Antigen ; Interferon-gamma (82115-62-6)
Language	English
Publishing date	2021-03-16
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, N.I.H., Intramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2719863-7
ISSN	2051-1426 ; 2051-1426
ISSN (online)	2051-1426
ISSN	2051-1426
DOI	10.1136/jitc-2020-002128
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: A Randomized Phase II Trial of mFOLFOX6 + Bevacizumab Alone or with AdCEA Vaccine + Avelumab Immunotherapy for Untreated Metastatic Colorectal Cancer.

Redman, Jason M / Tsai, Yo-Ting / Weinberg, Benjamin A / Donahue, Renee N / Gandhy, Shruti / Gatti-Mays, Margaret E / Abdul Sater, Houssein / Bilusic, Marijo / Cordes, Lisa M / Steinberg, Seth M / Marte, Jennifer L / Jochems, Caroline / Kim, Sunnie S / Marshall, John L / McMahon, Sheri / Redmond, Erica / Schlom, Jeffrey / Gulley, James L / Strauss, Julius

The oncologist

2022 Volume 27, Issue 3, Page(s) 198–209

Abstract: Background: FOLFOX plus bevacizumab is a standard of care (SOC) for first-line treatment of microsatellite-stable metastatic colorectal cancer (MSS mCRC). This study randomized patients to SOC or SOC plus avelumab (anti-PD-L1) plus CEA-targeted vaccine.! ...

Abstract	Background: FOLFOX plus bevacizumab is a standard of care (SOC) for first-line treatment of microsatellite-stable metastatic colorectal cancer (MSS mCRC). This study randomized patients to SOC or SOC plus avelumab (anti-PD-L1) plus CEA-targeted vaccine. Methods: Patients with untreated MSS mCRC enrolled to a lead-in arm assessing safety of SOC + immuno-oncology agents (IO). Next, patients were randomized to SOC or SOC + IO. The primary endpoint was progression-free survival (PFS). Multiple immune parameters were analyzed. Results: Six patients enrolled to safety lead-in, 10 randomized to SOC, and 10 to SOC + IO. There was no difference in median PFS comparing SOC versus SOC + IO (8.8 months (95% CI: 3.3-17.0 months) versus 10.1 months (95% CI: 3.6-16.1 months), respectively; hazard ratio 1.061 [P = .91; 95% CI: 0.380-2.966]). The objective response rate was 50% in both arms. Of patients analyzed, most (8/11) who received SOC + IO developed multifunctional CD4+/CD8+ T-cell responses to cascade antigens MUC1 and/or brachyury, compared to 1/8 who received SOC alone (P = .020). We detected post-treatment changes in immune parameters that were distinct to the SOC and SOC + IO treatment arms. Accrual closed after an unplanned analysis predicted a low likelihood of meeting the primary endpoint. Conclusions: SOC + IO generated multifunctional MUC1- and brachyury-specific CD4+/CD8+ T cells despite concurrent chemotherapy. Although a tumor-directed immune response is necessary for T-cell-mediated antitumor activity, it was not sufficient to improve PFS. Adding agents that increase the number and function of effector cells may be required for clinical benefit.
MeSH term(s)	Antibodies, Monoclonal, Humanized/therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/adverse effects ; Bevacizumab/therapeutic use ; Colorectal Neoplasms/drug therapy ; Colorectal Neoplasms/pathology ; Humans ; Immunotherapy ; Vaccines/therapeutic use
Chemical Substances	Antibodies, Monoclonal, Humanized ; Vaccines ; Bevacizumab (2S9ZZM9Q9V) ; avelumab (KXG2PJ551I)
Language	English
Publishing date	2022-03-11
Publishing country	England
Document type	Clinical Trial, Phase II ; Journal Article ; Randomized Controlled Trial ; Research Support, N.I.H., Intramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1409038-7
ISSN	1549-490X ; 1083-7159
ISSN (online)	1549-490X
ISSN	1083-7159
DOI	10.1093/oncolo/oyab046
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 4845: 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)
Zs.MO 494: Show issues

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article: Lung cancer trends: smoking, obesity, and sex assessed in the Staten Island University's lung cancer patients.

Gupta, Shilpi / Hassan, Samer / Bhatt, Vijaya R / Abdul Sater, Houssein / Dilawari, Asma

International journal of general medicine

2014 Volume 7, Page(s) 333–337

Abstract: Introduction: The incidence of lung cancer in the United States decreased by 1.8% from 1991 to 2005 while it increased by 0.5% in females. We assessed whether nonsmokers afflicted with lung cancer at Staten Island University Hospital are ... ...

Abstract	Introduction: The incidence of lung cancer in the United States decreased by 1.8% from 1991 to 2005 while it increased by 0.5% in females. We assessed whether nonsmokers afflicted with lung cancer at Staten Island University Hospital are disproportionately female in comparison to national averages. We also evaluated different factors including race, histology, and body mass index (BMI) in correlation with smoking history. Methods: A retrospective chart review was conducted from 2005 to 2011 on 857 patients. Patients were divided into two groups according to their smoking status: current or ever-smokers, and former or never-smokers. A chi-square test for categorical data and multivariate logistic regression analyses was used to study the relation between BMI and the other clinical and demographic data. Results: Forty-nine percent of patients were men and 51% were women with a mean age at diagnosis of 67.8 years. Current smokers were most common (50.2%) followed by ever-smokers (18.2%), former smokers (15.8%) and never-smokers (15.6%). Forty eight percent had stage IV lung cancer upon presentation. Never-smokers with lung cancer were 24 times more likely to be females. However, the proportion of female former smokers (31.6%) was lower than the proportion of male former smokers (68.4%) (P=0.001). There was no significant association between American Joint Committee on Cancer (AJCC) stage, sex, race, and histological type in the two smoking groups. Current/ever-smokers tended to be younger at age of diagnosis (P=0.0003). BMI was lower in the current/ever-smokers (26.8 kg/m(2)) versus former/never-smokers (28.8) in males (P=0.0005). BMI was significantly higher in males (30.26) versus females (25.25) in the never-smoker category (P=0.004). Current smokers, compared to others, had a lower BMI in males (26.4 versus 28.3; P=0.0001) and females (25.5 versus 26.9; P=0.013) but the mean BMI for all groups was in the overweight/obese range. Conclusion: Our population of lung cancer patients although demographically distinct, reflects a similar proportion of afflicted nonsmokers to the national population. Smoking is a major risk factor for lung cancer, but there is also a possible direct correlation with BMI that would support obesity as a potential risk factor for lung cancer.
Language	English
Publishing date	2014-07-02
Publishing country	New Zealand
Document type	Journal Article
ZDB-ID	2452220-X
ISSN	1178-7074
ISSN	1178-7074
DOI	10.2147/IJGM.S55806
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Tumor control via targeting PD-L1 with chimeric antigen receptor modified NK cells.

Robbins, Yvette / Greene, Sarah / Friedman, Jay / Clavijo, Paul E / Van Waes, Carter / Fabian, Kellsye P / Padget, Michelle R / Abdul Sater, Houssein / Lee, John H / Soon-Shiong, Patrick / Gulley, James / Schlom, Jeffrey / Hodge, James W / Allen, Clint T

eLife

2020 Volume 9

Abstract: Failed T cell-based immunotherapies in the presence of genomic alterations in antigen presentations pathways may be overcome by NK cell-based immunotherapy. This approach may still be limited by the presence of immunosuppressive myeloid populations. Here, ...

Abstract	Failed T cell-based immunotherapies in the presence of genomic alterations in antigen presentations pathways may be overcome by NK cell-based immunotherapy. This approach may still be limited by the presence of immunosuppressive myeloid populations. Here, we demonstrate that NK cells (haNKs) engineered to express a PD-L1 chimeric antigen receptor (CAR) haNKs killed a panel of human and murine head and neck cancer cells at low effector-to-target ratios in a PD-L1-dependent fashion. Treatment of syngeneic tumors resulted in CD8 and PD-L1-dependent tumor rejection or growth inhibition and a reduction in myeloid cells endogenously expressing high levels of PD-L1. Treatment of xenograft tumors resulted in PD-L1-dependent tumor growth inhibition. PD-L1 CAR haNKs reduced levels of macrophages and other myeloid cells endogenously expressing high PD-L1 in peripheral blood from patients with head and neck cancer. The clinical study of PD-L1 CAR haNKs is warranted.
MeSH term(s)	Animals ; B7-H1 Antigen/metabolism ; Cell Line ; Cell Line, Tumor ; Humans ; Killer Cells, Natural/physiology ; Mice ; Mice, Inbred C57BL ; Mice, Inbred NOD ; Receptors, Chimeric Antigen/metabolism ; Squamous Cell Carcinoma of Head and Neck/metabolism
Chemical Substances	B7-H1 Antigen ; CD274 protein, human ; Cd274 protein, mouse ; Receptors, Chimeric Antigen
Language	English
Publishing date	2020-07-07
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Intramural
ZDB-ID	2687154-3
ISSN	2050-084X ; 2050-084X
ISSN (online)	2050-084X
ISSN	2050-084X
DOI	10.7554/eLife.54854
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

To top

More links

Kategorien

Order via subito

More links

Kategorien

Order via subito

Inter-library loan at ZB MED

More links

Kategorien

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

Order via subito

More links

Kategorien

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito

More links

Kategorien

Order via subito