Online citations, reference lists, and bibliographies.
Please confirm you are human
(Sign Up for free to never see this)
← Back to Search

Pilot And Feasibility Trial Evaluating Immuno-Gene Therapy Of Malignant Mesothelioma Using Intrapleural Delivery Of Adenovirus-IFNα Combined With Chemotherapy

D. Sterman, E. Alley, J. Stevenson, J. Friedberg, S. Metzger, A. Recio, Edmund K. Moon, A. Haas, A. Vachani, S. Katz, J. Sun, D. Heitjan, W. Hwang, L. Litzky, J. Yearley, K. S. Tan, E. Papasavvas, P. Kennedy, L. Montaner, K. Cengel, C. Simone, M. Culligan, C. Langer, S. Albelda
Published 2016 · Medicine

Save to my Library
Download PDF
Analyze on Scholarcy
Share
Purpose: “In situ vaccination” using immunogene therapy has the ability to induce polyclonal antitumor responses directed by the patient's immune system. Experimental Design: Patients with unresectable malignant pleural mesothelioma (MPM) received two intrapleural doses of a replication-defective adenoviral vector containing the human IFNα2b gene (Ad.IFN) concomitant with a 14-day course of celecoxib followed by chemotherapy. Primary outcomes were safety, toxicity, and objective response rate; secondary outcomes included progression-free and overall survival. Biocorrelates on blood and tumor were measured. Results: Forty subjects were treated: 18 received first-line pemetrexed-based chemotherapy, 22 received second-line chemotherapy with pemetrexed (n = 7) or gemcitabine (n = 15). Treatment was generally well tolerated. The overall response rate was 25%, and the disease control rate was 88%. Median overall survival (MOS) for all patients with epithelial histology was 21 months versus 7 months for patients with nonepithelial histology. MOS in the first-line cohort was 12.5 months, whereas MOS for the second-line cohort was 21.5 months, with 32% of patients alive at 2 years. No biologic parameters were found to correlate with response, including numbers of activated blood T cells or NK cells, regulatory T cells in blood, peak levels of IFNα in blood or pleural fluid, induction of antitumor antibodies, nor an immune-gene signature in pretreatment biopsies. Conclusions: The combination of intrapleural Ad.IFN, celecoxib, and chemotherapy proved safe in patients with MPM. OS rate was significantly higher than historical controls in the second-line group. Results of this study support proceeding with a multicenter randomized clinical trial of chemo-immunogene therapy versus standard chemotherapy alone. Clin Cancer Res; 22(15); 3791–800. ©2016 AACR.
This paper references
10.1634/theoncologist.2010-0129
Therapeutic cancer vaccines in prostate cancer: the paradox of improved survival without changes in time to progression.
R. Madan (2010)
10.1038/nrc1613
Immunotherapy and chemotherapy — a practical partnership
R. Lake (2005)
Pleural treatment with recombinant gamma-interferon in early stage malignant pleural mesothelioma
C Boutin (1994)
10.1165/rcmb.2010-0026RT
Gene therapy for mesothelioma and lung cancer.
A. Vachani (2010)
10.1016/j.juro.2013.03.030
Phase I trial of intravesical recombinant adenovirus mediated interferon-α2b formulated in Syn3 for Bacillus Calmette-Guérin failures in nonmuscle invasive bladder cancer.
C. Dinney (2013)
10.1200/JCO.2012.44.3762
Predictive gene signature in MAGE-A3 antigen-specific cancer immunotherapy.
Fernando Ulloa-Montoya (2013)
Multifaceted roles of PGE 2 in in fl ammation and cancer
M Nakanishi (2013)
10.1007/s00262-005-0089-3
NK cell activation by dendritic cell vaccine: a mechanism of action for clinical activity
T. Osada (2005)
10.1016/J.BIOCHI.2007.04.006
Interferon-α and cancer : Mechanisms of action and new perspectives of clinical use
M. Ferrantini (2007)
10.1038/mt.2010.159
Chemotherapy delivered after viral immunogene therapy augments antitumor efficacy via multiple immune-mediated mechanisms.
Z. Fridlender (2010)
10.1164/rccm.201103-0554CR
A trial of intrapleural adenoviral-mediated Interferon-α2b gene transfer for malignant pleural mesothelioma.
D. Sterman (2011)
10.4161/onci.26218
Immunological effects of the TGFβ-blocking antibody GC1008 in malignant pleural mesothelioma patients
J. Stevenson (2013)
10.1002/1097-0142(19941101)74:9<2460::AID-CNCR2820740912>3.0.CO;2-N
Intrapleural treatment with recombinant gamma‐interferon in early stage malignant pleural mesothelioma
C. Boutin (1994)
10.1158/1078-0432.CCR-07-0403
A Phase I Clinical Trial of Single-Dose Intrapleural IFN-β Gene Transfer for Malignant Pleural Mesothelioma and Metastatic Pleural Effusions: High Rate of Antitumor Immune Responses
D. Sterman (2007)
10.1158/1078-0432.CCR-14-1298
Cisplatin-Induced Antitumor Immunomodulation: A Review of Preclinical and Clinical Evidence
A. D. de Biasi (2014)
10.1634/theoncologist.2014-0122
Current issues in malignant pleural mesothelioma evaluation and management.
J. Ai (2014)
Immunological effects of anti-transforming growth factor-beta (TGF-beta) antibody GC1008 in cancer patients with malignant pleural mesothelioma (MPM)
J P Stevenson (2013)
10.1155/2010/380697
Vaccines against Human Carcinomas: Strategies to Improve Antitumor Immune Responses
C. Palena (2010)
10.1158/1078-0432.CCR-05-1178
Cycloxygenase-2 Inhibition Augments the Efficacy of a Cancer Vaccine
A. Haas (2006)
10.1038/bjc.2014.478
Factors associated with survival in a large series of patients with malignant pleural mesothelioma in New South Wales
A. Linton (2014)
10.1200/JCO.2013.49.2157
Prediction of response to anticancer immunotherapy using gene signatures.
E. Wang (2013)
10.1089/hum.2013.235
Adenovirus-based vaccines for fighting infectious diseases and cancer: progress in the field.
Dragomira Majhen (2014)
10.1038/mt.2009.309
A phase I trial of repeated intrapleural adenoviral-mediated interferon-beta gene transfer for mesothelioma and metastatic pleural effusions.
D. Sterman (2010)
10.1007/s00262-011-1172-6
An immune-active tumor microenvironment favors clinical response to ipilimumab
R. Ji (2011)
10.1016/j.immuni.2008.02.020
Human effector and memory CD8+ T cell responses to smallpox and yellow fever vaccines.
Joseph D. Miller (2008)
10.1016/j.lungcan.2011.08.011
Second-line chemotherapy in malignant pleural mesothelioma: results of a retrospective multicenter survey.
P. Zucali (2012)
10.1093/jnci/djq310
Improved Endpoints for Cancer Immunotherapy Trials
A. Hoos (2010)
10.1093/ANNONC/MDH059
Modified RECIST criteria for assessment of response in malignant pleural mesothelioma.
M. Byrne (2004)
Interferon-alpha and cancer: mechanisms of action and new perspectives of clinical use.
M. Ferrantini (2007)
10.1038/mt.2009.309
A Phase I Trial of Repeated Intrapleural Adenoviral-mediated Interferon-β Gene Transfer for Mesothelioma and Metastatic Pleural Effusions.
D. Sterman (2010)
10.1200/JCO.2014.56.2736
Pooled Analysis of Long-Term Survival Data From Phase II and Phase III Trials of Ipilimumab in Unresectable or Metastatic Melanoma.
D. Schadendorf (2015)
10.1158/2326-6066.CIR-13-0020
Increased Frequency of ICOS+ CD4 T Cells as a Pharmacodynamic Biomarker for Anti-CTLA-4 Therapy
D. Ng Tang (2013)
Immunological effects of anti - transforming growth factor - beta ( TGF - beta ) antibodyGC 1008 in cancer patients withmalignant pleuralmesothelioma ( MPM )
JP Stevenson (2013)
Second-line chemotherapy in malignant pleural mesothemioma: Results of a retrospective multicenter survey. Lung Cancer 2012;75:360–67
PA Zucali (2012)
10.1038/nrclinonc.2014.111
Therapeutic vaccines for cancer: an overview of clinical trials
I. Melero (2014)
10.1016/S1470-2045(13)70381-4
Tremelimumab for patients with chemotherapy-resistant advanced malignant mesothelioma: an open-label, single-arm, phase 2 trial.
L. Calabrò (2013)
10.1007/s00281-012-0342-8
Multifaceted roles of PGE2 in inflammation and cancer
M. Nakanishi (2012)
10.1007/978-1-349-86135-4_11
Immunological Aspects of Cancer Chemotherapy
K. Calman (1980)
10.1111/j.1399-0039.2009.01275.x
Chemoimmunotherapy: an emerging strategy for the treatment of malignant mesothelioma.
M. McCoy (2009)
10.1089/jir.2011.0077
Interferon-α as antiviral and antitumor vaccine adjuvants: mechanisms of action and response signature.
E. Aricò (2012)



This paper is referenced by
10.1016/j.lungcan.2018.07.007
Current efforts in research of pleural mesothelioma-An analysis of the ClinicalTrials.gov registry.
Krisztian Süveg (2018)
10.1038/s41467-018-06890-y
Targeting IFNα to tumor by anti-PD-L1 creates feedforward antitumor responses to overcome checkpoint blockade resistance
Y. Liang (2018)
10.1183/16000617.0063-2016
Malignant pleural mesothelioma: an update on investigation, diagnosis and treatment
A. Bibby (2016)
10.2217/imt-2017-0026
Overcoming barriers of car T-cell therapy in patients with mesothelin-expressing cancers.
Mark H. O’Hara (2017)
MALIGNANT PLEURAL MESOTHELIOMA : SPOTLIGHT ON RECENT ADVANCES IN DIAGNOSIS AND TREATMENT
Aline N. Zouk (2017)
10.21037/atm.2017.03.81
Novel immunotherapy clinical trials in malignant pleural mesothelioma.
Z. Tano (2017)
10.1039/C8RA02580K
Delivery of interleukin-22 binding protein (IL-22BP) gene by cationic micelle for colon cancer gene therapy
Ke Men (2018)
10.1016/J.RMR.2017.07.025
Immunothérapie anti-tumorale dans le mésothéliome pleural malin
A. Scherpereel (2018)
10.3390/cancers9090115
Chimeric Antigen Receptor (CAR) T Cell Therapy for Malignant Pleural Mesothelioma (MPM)
Astero Klampatsa (2017)
10.21037/jtd.2018.05.73
Combining immunotherapy with radiation therapy in thoracic oncology.
S. Badiyan (2018)
10.1038/srep36829
Intrapleural Adenoviral-mediated Endothelial Cell Protein C Receptor Gene Transfer Suppresses the Progression of Malignant Pleural Mesothelioma in a Mouse Model
S. Keshava (2016)
10.1080/2162402X.2019.1638211
Phenotypic and functional analysis of malignant mesothelioma tumor-infiltrating lymphocytes
Astero Klampatsa (2019)
10.3390/cancers12051139
Expanding the Spectrum of Adenoviral Vectors for Cancer Therapy
J. Gao (2020)
10.1007/s13346-020-00724-5
Cyclodextrins in drug delivery: applications in gene and combination therapy
Rebecca M. Haley (2020)
10.1055/s-0039-1693406
Malignant Mesothelioma: Has Anything Changed?
Roger Y Kim (2019)
10.1016/j.ymthe.2018.02.015
Phase I Study of Intrapleural Gene-Mediated Cytotoxic Immunotherapy in Patients with Malignant Pleural Effusion.
C. Aggarwal (2018)
10.2147/IJN.S186344
Pemetrexed-loaded nanoparticles targeted to malignant pleural mesothelioma cells: an in vitro study
E. Cova (2019)
10.7759/cureus.4102
First-ever Abscopal Effect after Palliative Radiotherapy and Immuno-gene Therapy for Malignant Pleural Mesothelioma
A. Barsky (2019)
10.1007/978-3-030-28891-4_5
Regional Gene Therapy for Cancer
L. Cherkassky (2020)
10.2147/IJN.S237536
The Safety and Exploration of the Pharmacokinetics of Intrapleural Liposomal Curcumin
A. Hocking (2020)
10.1016/j.rmed.2017.11.015
Progress and challenges in Mesothelioma: From bench to bedside.
K. Blyth (2018)
10.1097/MCP.0000000000000489
Updates in the diagnosis and treatment of malignant pleural mesothelioma
D. Katzman (2018)
10.1016/S1877-1203(16)30135-5
Traitement du mésothéliome pleural malin en 2016
A. Scherpereel (2016)
10.1111/resp.12822
If they don't degrade can indwelling pleural catheters evolve?
J. Akulian (2016)
10.1089/hum.2016.152
Genetic Modification of the Lung Directed Toward Treatment of Human Disease.
D. Sondhi (2017)
10.1016/S1470-2045(18)30100-1
Novel therapies for malignant pleural mesothelioma.
A. Scherpereel (2018)
10.3389/fonc.2017.00179
Oncolytic Viral Therapy for Mesothelioma
D. Pease (2017)
10.1038/nrc.2017.42
Novel insights into mesothelioma biology and implications for therapy
T. Yap (2017)
10.1164/rccm.201807-1415ST
Management of Malignant Pleural Effusions. An Official ATS/STS/STR Clinical Practice Guideline
D. Feller-Kopman (2018)
10.1155/2020/2950751
Malignant Pleural Effusion: Diagnosis and Management
L. Ferreiro (2020)
10.1007/s13665-017-0179-7
Chemotherapy for Malignant Pleural Mesothelioma: Past, Present and Future
A. Scherpereel (2017)
10.21037/tlcr.2017.04.01
Immunotherapy and radiation therapy for malignant pleural mesothelioma.
E. Alley (2017)
See more
Semantic Scholar Logo Some data provided by SemanticScholar