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Article ; Online: Clinical and molecular effects of oral CCR4 antagonist RPT193 in atopic dermatitis: A Phase 1 study.

Bissonnette, Robert / DuBois, Janet / Facheris, Paola / Del Duca, Ester / Kim, Madeline / Correa Da Rosa, Joel / Trujillo, Damian L / Bose, Swaroop / Pagan, Angel D / Wustrow, David / Brockstedt, Dirk G / Wong, Brian / Kassner, Paul D / Jankicevic, Jasmina / Ho, William / Cheng, Laurence E / Guttman-Yassky, Emma

Allergy

2023 Volume 79, Issue 4, Page(s) 924–936

Abstract: Background: RPT193 is an orally administered small molecule antagonist of the human C-C motif chemokine receptor 4 (CCR4) that inhibits the migration and downstream activation of T-helper Type 2 (Th2) cells. We investigated single- and multiple- ... ...

Abstract	Background: RPT193 is an orally administered small molecule antagonist of the human C-C motif chemokine receptor 4 (CCR4) that inhibits the migration and downstream activation of T-helper Type 2 (Th2) cells. We investigated single- and multiple-ascending doses of RPT193 in healthy subjects, and multiple doses of RPT193 in subjects with moderate-to-severe atopic dermatitis (AD). Methods: This was a first-in-human randomized, placebo-controlled Phase 1a/1b monotherapy study (NCT04271514) to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and CCR4 surface receptor occupancy in eligible healthy subjects and subjects with moderate-to-severe AD. Clinical efficacy and skin biomarker effects of RPT193 monotherapy were assessed as exploratory endpoints in AD subjects. Results: In healthy (n = 72) and AD subjects (n = 31), once-daily RPT193 treatment was generally well tolerated, with no serious adverse events reported and all treatment-emergent adverse events reported as mild/moderate. In AD subjects, numerically greater improvements in clinical efficacy endpoints were observed with RPT193 monotherapy versus placebo up to the end of the treatment period (Day 29), with statistically significant improvement, compared to Day 29 and placebo, observed 2 weeks after the end of treatment (Day 43) on several endpoints (p < .05). Moreover, significant changes in the transcriptional profile were seen in skin biopsies of RPT193-treated versus placebo-treated subjects at Day 29, which were also significantly correlated with improvements in clinical efficacy measures. Conclusions: To our knowledge, this is the first clinical study with an oral CCR4 antagonist that showed clinical improvement coupled with modulation of the cutaneous transcriptomic profile in an inflammatory skin disease.
MeSH term(s)	Humans ; Dermatitis, Atopic/drug therapy ; Dermatitis, Atopic/pathology ; Skin/pathology ; Th2 Cells/pathology ; Treatment Outcome ; Double-Blind Method ; Severity of Illness Index ; Receptors, CCR4/therapeutic use
Chemical Substances	CCR4 protein, human ; Receptors, CCR4
Language	English
Publishing date	2023-11-20
Publishing country	Denmark
Document type	Randomized Controlled Trial ; Clinical Trial, Phase I ; Journal Article
ZDB-ID	391933-x
ISSN	1398-9995 ; 0105-4538
ISSN (online)	1398-9995
ISSN	0105-4538
DOI	10.1111/all.15949
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Article ; Online: EBV+ tumors exploit tumor cell-intrinsic and -extrinsic mechanisms to produce regulatory T cell-recruiting chemokines CCL17 and CCL22.

Jorapur, Aparna / Marshall, Lisa A / Jacobson, Scott / Xu, Mengshu / Marubayashi, Sachie / Zibinsky, Mikhail / Hu, Dennis X / Robles, Omar / Jackson, Jeffrey J / Baloche, Valentin / Busson, Pierre / Wustrow, David / Brockstedt, Dirk G / Talay, Oezcan / Kassner, Paul D / Cutler, Gene

PLoS pathogens

2022 Volume 18, Issue 1, Page(s) e1010200

Abstract: The Epstein-Barr Virus (EBV) is involved in the etiology of multiple hematologic and epithelial human cancers. EBV+ tumors employ multiple immune escape mechanisms, including the recruitment of immunosuppressive regulatory T cells (Treg). Here, we show ... ...

Abstract	The Epstein-Barr Virus (EBV) is involved in the etiology of multiple hematologic and epithelial human cancers. EBV+ tumors employ multiple immune escape mechanisms, including the recruitment of immunosuppressive regulatory T cells (Treg). Here, we show some EBV+ tumor cells express high levels of the chemokines CCL17 and CCL22 both in vitro and in vivo and that this expression mirrors the expression levels of expression of the EBV LMP1 gene in vitro. Patient samples from lymphoblastic (Hodgkin lymphoma) and epithelial (nasopharyngeal carcinoma; NPC) EBV+ tumors revealed CCL17 and CCL22 expression of both tumor cell-intrinsic and -extrinsic origin, depending on tumor type. NPCs grown as mouse xenografts likewise showed both mechanisms of chemokine production. Single cell RNA-sequencing revealed in vivo tumor cell-intrinsic CCL17 and CCL22 expression combined with expression from infiltrating classical resident and migratory dendritic cells in a CT26 colon cancer mouse tumor engineered to express LMP1. These data suggest that EBV-driven tumors employ dual mechanisms for CCL17 and CCL22 production. Importantly, both in vitro and in vivo Treg migration was effectively blocked by a novel, small molecule antagonist of CCR4, CCR4-351. Antagonism of the CCR4 receptor may thus be an effective means of activating the immune response against a wide spectrum of EBV+ tumors.
MeSH term(s)	Animals ; Chemokine CCL17/immunology ; Chemokine CCL22/immunology ; Epstein-Barr Virus Infections/complications ; Epstein-Barr Virus Infections/immunology ; Herpesvirus 4, Human ; Heterografts ; Hodgkin Disease/immunology ; Hodgkin Disease/virology ; Humans ; Mice ; Nasopharyngeal Carcinoma/immunology ; Nasopharyngeal Carcinoma/virology ; Nasopharyngeal Neoplasms/immunology ; Nasopharyngeal Neoplasms/virology ; Neoplasms/immunology ; Neoplasms/virology ; T-Lymphocytes, Regulatory/immunology
Chemical Substances	Chemokine CCL17 ; Chemokine CCL22
Language	English
Publishing date	2022-01-13
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2205412-1
ISSN	1553-7374 ; 1553-7374
ISSN (online)	1553-7374
ISSN	1553-7374
DOI	10.1371/journal.ppat.1010200
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Article ; Online: Promises and challenges for the development of Listeria monocytogenes-based immunotherapies.

Brockstedt, Dirk G / Dubensky, Thomas W

Expert review of vaccines

2008 Volume 7, Issue 7, Page(s) 1069–1084

Abstract: Active immunotherapy has shown great promise in preclinical models for the treatment of infectious and malignant disease. Yet, these promising results have not translated into approved therapies. One of the major deficits of active immunotherapies tested ...

Abstract	Active immunotherapy has shown great promise in preclinical models for the treatment of infectious and malignant disease. Yet, these promising results have not translated into approved therapies. One of the major deficits of active immunotherapies tested to date in advanced clinical studies has been their inability to stimulate both arms of the immune system appropriately. The interest in using recombinant bacteria as vaccine vectors for active immunotherapy derives in part from their ability to stimulate multiple innate immune pathways and, at the same time, to deliver antigen for presentation to the adaptive immune system. This review will focus on the development of live-attenuated and killed strains of the intracellular bacterium Listeria monocytogenes for treatment of chronic infections and cancer. Early clinical trials intended to demonstrate safety as well as proof of concept have recently been initiated in several indications. Advances in molecular engineering as well as successes and challenges for clinical development of L. monocytogenes-based vaccines will be discussed.
MeSH term(s)	Bacterial Infections/immunology ; Bacterial Infections/therapy ; Bacterial Vaccines/genetics ; Bacterial Vaccines/immunology ; Cancer Vaccines/genetics ; Cancer Vaccines/immunology ; Humans ; Immunotherapy/methods ; Listeria monocytogenes/genetics ; Listeria monocytogenes/immunology ; Neoplasms/immunology ; Neoplasms/therapy
Chemical Substances	Bacterial Vaccines ; Cancer Vaccines
Language	English
Publishing date	2008-09
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2181284-6
ISSN	1744-8395 ; 1476-0584
ISSN (online)	1744-8395
ISSN	1476-0584
DOI	10.1586/14760584.7.7.1069
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Article ; Online: Clinical development of Listeria monocytogenes-based immunotherapies.

Le, Dung T / Dubenksy, Thomas W / Brockstedt, Dirk G

Seminars in oncology

2012 Volume 39, Issue 3, Page(s) 311–322

Abstract: Active immunotherapy targeting dendritic cells (DCs) has shown great promise in preclinical models and in human clinical trials for the treatment of malignant disease. Sipuleucel-T (Provenge, Dendreon, Seattle, WA), which consists of antigen-loaded ... ...

Abstract	Active immunotherapy targeting dendritic cells (DCs) has shown great promise in preclinical models and in human clinical trials for the treatment of malignant disease. Sipuleucel-T (Provenge, Dendreon, Seattle, WA), which consists of antigen-loaded dendritic cells (DCs), recently became the first targeted therapeutic cancer vaccine to be approved by the US Food and Drug Administration (FDA). However, ex vivo therapies such as Provenge have practical limitations and elicit an immune response with limited scope. By contrast, live-attenuated Listeria monocytogenes (Lm) naturally targets DCs in vivo and stimulates both innate and adaptive cellular immunity. Lm-based vaccines engineered to express cancer antigens have demonstrated striking efficacy in several animal models and have resulted in encouraging anecdotal survival benefit in early human clinical trials. Two different Lm-based vaccine platforms have advanced into phase II clinical trials in cervical and pancreatic cancer. Future Lm-based clinical vaccine candidates are expected to feature polyvalent antigen expression and to be used in combination with other immunotherapies or conventional therapies such as radiotherapy and chemotherapy to augment efficacy.
MeSH term(s)	Animals ; Antigens, Neoplasm/genetics ; Antigens, Neoplasm/immunology ; Cancer Vaccines/genetics ; Cancer Vaccines/immunology ; Clinical Trials as Topic ; Dendritic Cells/immunology ; Dendritic Cells/microbiology ; Genetic Vectors/genetics ; Genetic Vectors/immunology ; Humans ; Immunotherapy/methods ; Listeria monocytogenes/genetics ; Listeria monocytogenes/immunology ; Lymphocyte Activation/immunology ; T-Lymphocytes/immunology
Chemical Substances	Antigens, Neoplasm ; Cancer Vaccines
Language	English
Publishing date	2012-05-17
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	189220-4
ISSN	1532-8708 ; 0093-7754
ISSN (online)	1532-8708
ISSN	0093-7754
DOI	10.1053/j.seminoncol.2012.02.008
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Article: Radiation therapy combined with

Lim, Joanne Yh / Brockstedt, Dirk G / Lord, Edith M / Gerber, Scott A

Oncoimmunology

2014 Volume 3, Page(s) e29028

Abstract: Conceptually, the immune system may profoundly influence the efficacy of radiation therapy. Compelling evidence has recently emerged revealing the capacity of local radiation therapy (RT) to induce antitumor immune responses and sparked interest in ... ...

Abstract	Conceptually, the immune system may profoundly influence the efficacy of radiation therapy. Compelling evidence has recently emerged revealing the capacity of local radiation therapy (RT) to induce antitumor immune responses and sparked interest in combining RT with immunotherapy to promote tumor-specific immunity. A
Language	English
Publishing date	2014-06-03
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2645309-5
ISSN	2162-402X ; 2162-4011
ISSN (online)	2162-402X
ISSN	2162-4011
DOI	10.4161/onci.29028
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Article ; Online: Single-Cell Immune Competency Signatures Associate with Survival in Phase II GVAX and CRS-207 Randomized Studies in Patients with Metastatic Pancreatic Cancer.

Nair, Nitya / Chen, Shih-Yu / Lemmens, Ed / Chang, Serena / Le, Dung T / Jaffee, Elizabeth M / Murphy, Aimee / Whiting, Chan / Müller, Thomas / Brockstedt, Dirk G

Cancer immunology research

2020 Volume 8, Issue 5, Page(s) 609–617

Abstract: The identification of biomarkers for patient stratification is fundamental to precision medicine efforts in oncology. Here, we identified two baseline, circulating immune cell subsets associated with overall survival in patients with metastatic ... ...

Abstract	The identification of biomarkers for patient stratification is fundamental to precision medicine efforts in oncology. Here, we identified two baseline, circulating immune cell subsets associated with overall survival in patients with metastatic pancreatic cancer who were enrolled in two phase II randomized studies of GVAX pancreas and CRS-207 immunotherapy. Single-cell mass cytometry was used to simultaneously measure 38 cell surface or intracellular markers in peripheral blood mononuclear cells obtained from a phase IIa patient subcohort (
MeSH term(s)	Aged ; Aged, 80 and over ; Bacterial Vaccines/therapeutic use ; Biomarkers, Tumor/blood ; Biomarkers, Tumor/immunology ; Cancer Vaccines/therapeutic use ; Female ; Flow Cytometry/methods ; GPI-Linked Proteins/immunology ; Humans ; Immunotherapy/methods ; Leukocytes, Mononuclear/drug effects ; Leukocytes, Mononuclear/immunology ; Leukocytes, Mononuclear/pathology ; Listeria monocytogenes/immunology ; Male ; Mass Spectrometry/methods ; Middle Aged ; Neoplasm Metastasis ; Pancreatic Neoplasms/drug therapy ; Pancreatic Neoplasms/immunology ; Pancreatic Neoplasms/mortality ; Prospective Studies ; Retrospective Studies ; Single-Cell Analysis ; Survival Rate ; Treatment Outcome
Chemical Substances	Bacterial Vaccines ; Biomarkers, Tumor ; Cancer Vaccines ; GPI-Linked Proteins ; GVAX vaccine ; mesothelin (J27WDC343N)
Language	English
Publishing date	2020-03-04
Publishing country	United States
Document type	Clinical Trial, Phase II ; Journal Article ; Multicenter Study ; Randomized Controlled Trial ; Research Support, N.I.H., Extramural ; 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-19-0650
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Article ; Online: Killed but metabolically active vaccines.

Dubensky, Thomas W / Skoble, Justin / Lauer, Peter / Brockstedt, Dirk G

Current opinion in biotechnology

2012 Volume 23, Issue 6, Page(s) 917–923

Abstract: Beginning in the 20th century and continuing into the new millennia, vaccines against numerous diseases have had an unquestioned principal role of both enhancing the quality of life and increasing life expectancy (Rappuoli R, Mandl CW, Black S, De ... ...

Abstract	Beginning in the 20th century and continuing into the new millennia, vaccines against numerous diseases have had an unquestioned principal role of both enhancing the quality of life and increasing life expectancy (Rappuoli R, Mandl CW, Black S, De Gregorio E: Vaccines for the twenty-first century society. Nat Rev Immunol 2011, 11:865-872). Despite this success and the development of sophisticated new vaccine technologies, there remain multiple infectious diseases including tuberculosis, malaria and AIDS that await an effective prophylactic vaccine. In addition, there have been recent clinical successes among individuals with cancer using vaccine treatment strategies-so-called therapeutic vaccines-that stimulate tumor specific immunity and increase survival (Kantoff PW, Higano CS, Shore ND, Berger ER, Small EJ, Penson DF, Redfern CH, Ferrari AC, Dreicer R, Sims RB, et al.: Sipuleucel-T immunotherapy for castration-resistant prostate cancer. New Engl J Med 2010, 363:411-422). Here we summarize a new class of vaccines termed Killed But Metabolically Active (KBMA). KBMA vaccines are whole pathogenic or attenuated organisms killed through photochemical inactivation and cannot cause disease, yet retain sufficient metabolic activity to initiate a potent immune response. KBMA vaccines have two broad applications. First, recombinant KBMA vaccines encoding selected antigens relevant to infectious disease or cancer can be used to elicit a desired immune response. In the second application, KBMA vaccines can be derived from attenuated forms of a targeted pathogen, allowing for the presentation of the entire antigenic repertoire to the immune system, of particular importance when the correlates of protection are unknown.
MeSH term(s)	Animals ; Cancer Vaccines/immunology ; Clinical Trials as Topic ; DNA Repair ; Ficusin ; Humans ; Leishmania/immunology ; Listeria monocytogenes/genetics ; Listeria monocytogenes/immunology ; Ultraviolet Rays ; Vaccines, Attenuated/immunology ; Vaccines, Inactivated/immunology ; Vaccines, Inactivated/radiation effects ; Vaccines, Inactivated/supply & distribution ; Vaccines, Synthetic/genetics ; Vaccines, Synthetic/immunology
Chemical Substances	Cancer Vaccines ; Vaccines, Attenuated ; Vaccines, Inactivated ; Vaccines, Synthetic ; Ficusin (KTZ7ZCN2EX)
Language	English
Publishing date	2012-12
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	1052045-4
ISSN	1879-0429 ; 0958-1669
ISSN (online)	1879-0429
ISSN	0958-1669
DOI	10.1016/j.copbio.2012.04.005
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Article ; Online: A Potent and Effective Suicidal

Hanson, William G / Benanti, Erin L / Lemmens, Edward E / Liu, Weiqun / Skoble, Justin / Leong, Meredith L / Rae, Chris S / Fassò, Marcella / Brockstedt, Dirk G / Chen, Chen / Portnoy, Daniel A / Dubensky, Thomas W / Lauer, Peter

Infection and immunity

2019 Volume 87, Issue 8

Abstract: ... Live- ... ...

Abstract	Live-attenuated
MeSH term(s)	Animals ; Bacterial Vaccines/immunology ; Female ; Immunotherapy ; Listeria monocytogenes/immunology ; Listeria monocytogenes/pathogenicity ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; T-Lymphocytes/immunology ; Vaccines, Attenuated/immunology ; Virulence
Chemical Substances	Bacterial Vaccines ; Vaccines, Attenuated
Language	English
Publishing date	2019-07-23
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	218698-6
ISSN	1098-5522 ; 0019-9567
ISSN (online)	1098-5522
ISSN	0019-9567
DOI	10.1128/IAI.00144-19
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Article ; Online: Tumors establish resistance to immunotherapy by regulating T

Marshall, Lisa A / Marubayashi, Sachie / Jorapur, Aparna / Jacobson, Scott / Zibinsky, Mikhail / Robles, Omar / Hu, Dennis Xiaozhou / Jackson, Jeffrey J / Pookot, Deepa / Sanchez, Jerick / Brovarney, Martin / Wadsworth, Angela / Chian, David / Wustrow, David / Kassner, Paul D / Cutler, Gene / Wong, Brian / Brockstedt, Dirk G / Talay, Oezcan

Journal for immunotherapy of cancer

2020 Volume 8, Issue 2

Abstract: Background: Checkpoint inhibitors (CPIs) such as anti-PD(L)-1 and anti-CTLA-4 antibodies have resulted in unprecedented rates of antitumor responses and extension of survival of patients with a variety of cancers. But some patients fail to respond or ... ...

Abstract	Background: Checkpoint inhibitors (CPIs) such as anti-PD(L)-1 and anti-CTLA-4 antibodies have resulted in unprecedented rates of antitumor responses and extension of survival of patients with a variety of cancers. But some patients fail to respond or initially respond but later relapse as they develop resistance to immune therapy. One of the tumor-extrinsic mechanisms for resistance to immune therapy is the accumulation of regulatory T cells (T Methods: We developed in vitro and in vivo models to assess T Results: Using a selective and highly potent, novel small molecule inhibitor of CCR4, we demonstrate that migration of CCR4 Conclusion: Taken together, we demonstrate that CCR4-dependent T Statement of significance: CPI upregulates CCL17 and CCL22 expression in tumors and increases T
MeSH term(s)	Animals ; Female ; Humans ; Immunotherapy/methods ; Mice ; Neoplasms/immunology ; Neoplasms/therapy ; Receptors, CCR4/immunology ; T-Lymphocytes, Regulatory/immunology ; Xenograft Model Antitumor Assays
Chemical Substances	CCR4 protein, human ; Ccr4 protein, mouse ; Receptors, CCR4
Language	English
Publishing date	2020-11-26
Publishing country	England
Document type	Journal Article ; 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-2020-000764
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Article ; Online: Clinical Response of Live-Attenuated,

Hassan, Raffit / Alley, Evan / Kindler, Hedy / Antonia, Scott / Jahan, Thierry / Honarmand, Somayeh / Nair, Nitya / Whiting, Chan C / Enstrom, Amanda / Lemmens, Ed / Tsujikawa, Takahiro / Kumar, Sushil / Choe, Gina / Thomas, Anish / McDougall, Katherine / Murphy, Aimee L / Jaffee, Elizabeth / Coussens, Lisa M / Brockstedt, Dirk G

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

2019 Volume 25, Issue 19, Page(s) 5787–5798

Abstract: Purpose: Malignant pleural mesothelioma (MPM) is an aggressive cancer associated with poor prognosis. CRS-207 is a live-attenuated : Patients and methods: Patients with unresectable MPM, ECOG 0 or 1, and adequate organ and pulmonary function were ... ...

Abstract	Purpose: Malignant pleural mesothelioma (MPM) is an aggressive cancer associated with poor prognosis. CRS-207 is a live-attenuated Patients and methods: Patients with unresectable MPM, ECOG 0 or 1, and adequate organ and pulmonary function were enrolled in this multicenter, open-label phase Ib study. They received two priming infusions of 1 × 10 Results: Of 35 evaluable patients, 89% (31/35) had disease control with one complete response (3%), 19 partial responses (54%), and 10 stable disease (29%). The estimated median duration of response was 5.0 months (95% CI, 3.9-11.5). The median PFS and OS were 7.5 (95% CI, 7.0-9.9) and 14.7 (95% CI, 11.2-21.9) months, respectively. Tumor size reduction was observed post-CRS-207 infusion prior to chemotherapy in 11 of 35 (31%) patients. No unexpected treatment-related serious adverse events or deaths were observed. IHC analysis of pre- and post-CRS-207 treatment tumor biopsies revealed possible reinvigoration and proliferation of T cells, increased infiltration of dendritic and natural killer cells, increased CD8:T Conclusions: Combination of CRS-207 and chemotherapy induced significant changes in the local tumor microenvironment and objective tumor responses in a majority of treated patients.
MeSH term(s)	Aged ; Aged, 80 and over ; Antineoplastic Combined Chemotherapy Protocols/adverse effects ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Cisplatin/administration & dosage ; Combined Modality Therapy ; Female ; GPI-Linked Proteins/immunology ; GPI-Linked Proteins/metabolism ; Humans ; Listeria monocytogenes/immunology ; Lung Neoplasms/immunology ; Lung Neoplasms/pathology ; Lung Neoplasms/therapy ; Male ; Mesothelin ; Mesothelioma/immunology ; Mesothelioma/pathology ; Mesothelioma/therapy ; Mesothelioma, Malignant ; Middle Aged ; Pemetrexed/administration & dosage ; Pleural Neoplasms/immunology ; Pleural Neoplasms/pathology ; Pleural Neoplasms/therapy ; Survival Rate ; Tumor Microenvironment
Chemical Substances	GPI-Linked Proteins ; Pemetrexed (04Q9AIZ7NO) ; Mesothelin (J27WDC343N) ; Cisplatin (Q20Q21Q62J)
Language	English
Publishing date	2019-07-01
Publishing country	United States
Document type	Clinical Trial, Phase I ; Journal Article ; Multicenter Study ; Research Support, N.I.H., Extramural ; Research Support, N.I.H., Intramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	1225457-5
ISSN	1557-3265 ; 1078-0432
ISSN (online)	1557-3265
ISSN	1078-0432
DOI	10.1158/1078-0432.CCR-19-0070
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