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Article: Combination Therapies for HPV-Associated Malignancies.

Smalley Rumfield, Claire / Schlom, Jeffrey / Jochems, Caroline

Journal of clinical & cellular immunology

2020 Volume 12, Issue 1

Abstract: Human papillomavirus (HPV)-associated malignancies cause almost all cases of cervical cancer in women, and a significant percentage of head and neck cancer, together totaling almost 5% of the global cancer burden, and representing an important public ... ...

Abstract	Human papillomavirus (HPV)-associated malignancies cause almost all cases of cervical cancer in women, and a significant percentage of head and neck cancer, together totaling almost 5% of the global cancer burden, and representing an important public health issue. The approval and use of two prophylactic HPV vaccines, Gardasil® and Cervarix®, have significantly decreased infections with HPV, but unfortunately, prophylactic vaccination does not treat established infections or malignancies resulting from HPV. Therefore, therapies for HPV-associated malignancies are necessary to improve the quality of life and survival in patients with these diseases. This review will detail new combinations of therapies in clinical development for HPV-associated malignancies.
Language	English
Publishing date	2020-12-28
Publishing country	United States
Document type	Journal Article
ZDB-ID	2684688-3
ISSN	2155-9899
ISSN	2155-9899
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Article ; Online: Immune correlates of clinical parameters in patients with HPV-associated malignancies treated with bintrafusp alfa.

Tsai, Yo-Ting / Strauss, Julius / Toney, Nicole J / Jochems, Caroline / Venzon, David J / Gulley, James L / Schlom, Jeffrey / Donahue, Renee N

Journal for immunotherapy of cancer

2022 Volume 10, Issue 4

Abstract: Purpose: Bintrafusp alfa is a bifunctional agent consisting of an anti-human PD-L1 antibody linked to two TGFβRII. It is designed to act both as a checkpoint inhibitor and to 'trap' TGFβ in the tumor microenvironment. Phase I and II clinical studies ... ...

Abstract	Purpose: Bintrafusp alfa is a bifunctional agent consisting of an anti-human PD-L1 antibody linked to two TGFβRII. It is designed to act both as a checkpoint inhibitor and to 'trap' TGFβ in the tumor microenvironment. Phase I and II clinical studies demonstrated clinical activity in patients with a range of human papillomavirus (HPV)-associated cancers. The purpose of the studies reported here was the interrogation of various aspects of the peripheral immunome in patients with HPV-associated cancers, both prior to and early in the treatment regimen of bintrafusp alfa to better understand the mode of action of the agent and to help define which patients are more likely to benefit from bintrafusp alfa treatment. Patients and methods: The peripheral immunome of patients (n=65) with HPV Results: Interrogation of the peripheral immunome prior to bintrafusp alfa treatment revealed several factors that associated with clinical response, including (1) higher levels of sCD27:sCD40L ratios, (2) lower levels of TGFβ1 and 12 additional factors associated with tumor mesenchymalization, and (3) higher CD8 Conclusions: These studies add insight into the mechanism of action of bintrafusp alfa and provide evidence that the interrogation of both cellular and soluble components of the peripheral immunome of patients with HPV-associated malignancies, either prior to or early in the therapeutic regimen, can provide information as to which patients are more likely to benefit with bintrafusp alfa therapy.
MeSH term(s)	Alphapapillomavirus ; CD8-Positive T-Lymphocytes/pathology ; Humans ; Immunologic Factors/therapeutic use ; Neoplasms/drug therapy ; Papillomaviridae ; Papillomavirus Infections/complications ; Papillomavirus Infections/drug therapy ; Papillomavirus Infections/pathology ; Tumor Microenvironment
Chemical Substances	Immunologic Factors
Language	English
Publishing date	2022-04-13
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-2022-004601
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Article: Therapeutic Vaccines for HPV-Associated Malignancies.

Smalley Rumfield, Claire / Roller, Nicholas / Pellom, Samuel Troy / Schlom, Jeffrey / Jochems, Caroline

ImmunoTargets and therapy

2020 Volume 9, Page(s) 167–200

Abstract: Human papillomavirus (HPV)-related malignancies are responsible for almost all cases of cervical cancer in women, and over 50% of all cases of head and neck carcinoma. Worldwide, HPV-positive malignancies account for 4.5% of the global cancer burden, or ... ...

Abstract	Human papillomavirus (HPV)-related malignancies are responsible for almost all cases of cervical cancer in women, and over 50% of all cases of head and neck carcinoma. Worldwide, HPV-positive malignancies account for 4.5% of the global cancer burden, or over 600,000 cases per year. HPV infection is a pressing public health issue, as more than 80% of all individuals have been exposed to HPV by age 50, representing an important target for vaccine development to reduce the incidence of cancer and the economic cost of HPV-related health issues. The approval of Gardasil
Language	English
Publishing date	2020-10-07
Publishing country	New Zealand
Document type	Journal Article ; Review
ISSN	2253-1556
ISSN	2253-1556
DOI	10.2147/ITT.S273327
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Article ; Online: Immunomodulation to enhance the efficacy of an HPV therapeutic vaccine.

Smalley Rumfield, Claire / Pellom, Samuel T / Morillon Ii, Y Maurice / Schlom, Jeffrey / Jochems, Caroline

Journal for immunotherapy of cancer

2020 Volume 8, Issue 1

Abstract: Background: While prophylactic human papillomavirus (HPV) vaccines will certainly reduce the incidence of HPV-associated cancers, these malignancies remain a major health issue. PDS0101 is a liposomal-based HPV therapeutic vaccine consisting of the ... ...

Abstract	Background: While prophylactic human papillomavirus (HPV) vaccines will certainly reduce the incidence of HPV-associated cancers, these malignancies remain a major health issue. PDS0101 is a liposomal-based HPV therapeutic vaccine consisting of the immune activating cationic lipid R-DOTAP and HLA-unrestricted HPV16 peptides that has shown in vivo CD8+ T cell induction and safety in a phase I study. In this report, we have employed the PDS0101 vaccine with two immune modulators previously characterized in preclinical studies and which are currently in phase II clinical trials. Bintrafusp alfa (M7824) is a first-in-class bifunctional fusion protein composed of the extracellular domains of the transforming growth factor-β receptor type II (TGFβRII) fused to a human IgG Methods: We employed TC-1 carcinoma (expressing HPV16 E6 and E7 and devoid of PDL1 expression) in a syngeneic mouse model in monotherapy and combination therapy studies to analyze antitumor effects and changes in immune cell types in the spleen and the TME. Results: As a monotherapy, the PDS0101 vaccine generated HPV-specific T cells and antitumor activity in mice bearing HPV-expressing mEER oropharyngeal and TC-1 lung carcinomas. When used as a monotherapy in the TC-1 model, NHS-IL12 elicited antitumor effects as well as an increase in CD8+ T cells in the TME. When used as a monotherapy, bintrafusp alfa did not elicit antitumor effects or any increase in T cells in the TME. When all three agents were used in combination, maximum antitumor effects were observed, which correlated with increases in T cells and T-cell clonality in the TME. Conclusion: These studies provide the rationale for the potential clinical use of combinations of agents that can (1) induce tumor-associated T-cell responses, (2) potentiate immune responses in the TME and (3) reduce immunosuppressive entities in the TME.
MeSH term(s)	Animals ; B7-H1 Antigen/antagonists & inhibitors ; B7-H1 Antigen/immunology ; CD8-Positive T-Lymphocytes/drug effects ; CD8-Positive T-Lymphocytes/immunology ; Cancer Vaccines/administration & dosage ; Cancer Vaccines/immunology ; Carcinoma/immunology ; Carcinoma/pathology ; Carcinoma/therapy ; Carcinoma/virology ; Cell Line, Tumor/transplantation ; Disease Models, Animal ; Female ; Human papillomavirus 16/immunology ; Humans ; Immune Checkpoint Inhibitors/administration & dosage ; Immunoconjugates/administration & dosage ; Immunogenicity, Vaccine ; Immunoglobulin G/administration & dosage ; Immunotherapy, Active/methods ; Interleukin-12/administration & dosage ; Lymphocytes, Tumor-Infiltrating/drug effects ; Lymphocytes, Tumor-Infiltrating/immunology ; Mice ; Oncogene Proteins, Viral/immunology ; Papillomavirus E7 Proteins/immunology ; Papillomavirus Infections/immunology ; Papillomavirus Infections/pathology ; Papillomavirus Infections/therapy ; Papillomavirus Infections/virology ; Papillomavirus Vaccines/administration & dosage ; Papillomavirus Vaccines/immunology ; Recombinant Fusion Proteins/administration & dosage ; Repressor Proteins/immunology ; Tumor Microenvironment/drug effects ; Tumor Microenvironment/immunology ; Vaccines, Subunit/administration & dosage ; Vaccines, Subunit/immunology
Chemical Substances	B7-H1 Antigen ; Cancer Vaccines ; Cd274 protein, mouse ; E6 protein, Human papillomavirus type 16 ; Immune Checkpoint Inhibitors ; Immunoconjugates ; Immunoglobulin G ; NHS-IL12 immunocytokine ; Oncogene Proteins, Viral ; Papillomavirus E7 Proteins ; Papillomavirus Vaccines ; Recombinant Fusion Proteins ; Repressor Proteins ; Vaccines, Subunit ; oncogene protein E7, Human papillomavirus type 16 ; Interleukin-12 (187348-17-0)
Language	English
Publishing date	2020-05-15
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Intramural
ZDB-ID	2719863-7
ISSN	2051-1426 ; 2051-1426
ISSN (online)	2051-1426
ISSN	2051-1426
DOI	10.1136/jitc-2020-000612
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Article ; Online: Preclinical study of a novel therapeutic vaccine for recurrent respiratory papillomatosis.

Lee, Maxwell Y / Metenou, Simon / Brough, Douglas E / Sabzevari, Helen / Bai, Ke / Jochems, Caroline / Schlom, Jeffrey / Allen, Clint T

NPJ vaccines

2021 Volume 6, Issue 1, Page(s) 86

Abstract: Activation of antigen-specific T-lymphocyte responses may be needed to cure disorders caused by chronic infection with low-risk human papillomavirus (lrHPV). Safe and effective adjuvant therapies for such disorders are needed. The safety and efficacy of ... ...

Abstract	Activation of antigen-specific T-lymphocyte responses may be needed to cure disorders caused by chronic infection with low-risk human papillomavirus (lrHPV). Safe and effective adjuvant therapies for such disorders are needed. The safety and efficacy of a novel gorilla adenovirus vaccine expressing a protein designed to elicit immune responses directed against HPV6 and HPV11, PRGN-2012, was studied using in vitro stimulation of T lymphocytes from patients with recurrent respiratory papillomatosis, in vivo vaccination studies, and therapeutic studies in mice bearing tumors expressing lrHPV antigen. PRGN-2012 treatment induces lrHPV antigen-specific responses in patient T lymphocytes. Vaccination of wild-type mice induces E6-specific T-lymphocyte responses without toxicity. In vivo therapeutic vaccination of mice bearing established HPV6 E6 expressing tumors results in HPV6 E6-specific CD8+ T-lymphocyte immunity of sufficient magnitude to induce tumor growth delay. The clinical study of PRGN-2012 in patients with disorders caused by chronic infection with lrHPV is warranted.
Language	English
Publishing date	2021-06-18
Publishing country	England
Document type	Journal Article
ISSN	2059-0105
ISSN (online)	2059-0105
DOI	10.1038/s41541-021-00348-x
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Article ; Online: Dual targeting of TGF-β and PD-L1 via a bifunctional anti-PD-L1/TGF-βRII agent: status of preclinical and clinical advances.

Lind, Hanne / Gameiro, Sofia R / Jochems, Caroline / Donahue, Renee N / Strauss, Julius / Gulley, James L / Palena, Claudia / Schlom, Jeffrey

Journal for immunotherapy of cancer

2020 Volume 8, Issue 1

Abstract: Immunosuppressive entities in the tumor microenvironment (TME) remain a major impediment to immunotherapeutic approaches for a majority of patients with cancer. While the immunosuppressive role of transforming growth factor-β (TGF-β) in the TME is well ... ...

Abstract	Immunosuppressive entities in the tumor microenvironment (TME) remain a major impediment to immunotherapeutic approaches for a majority of patients with cancer. While the immunosuppressive role of transforming growth factor-β (TGF-β) in the TME is well known, clinical studies to date with anti-TGF-β agents have led to limited success. The bifunctional agent bintrafusp alfa (previously designated M7824) has been developed in an attempt to address this issue. Bintrafusp alfa consists of an IgG
MeSH term(s)	Animals ; B7-H1 Antigen/metabolism ; Humans ; Immunotherapy/methods ; Mice ; Receptor, Transforming Growth Factor-beta Type II/metabolism ; Transforming Growth Factor beta/metabolism
Chemical Substances	B7-H1 Antigen ; CD274 protein, human ; Transforming Growth Factor beta ; Receptor, Transforming Growth Factor-beta Type II (EC 2.7.11.30) ; TGFBR2 protein, human (EC 2.7.11.30)
Language	English
Publishing date	2020-04-07
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Intramural ; Review
ZDB-ID	2719863-7
ISSN	2051-1426 ; 2051-1426
ISSN (online)	2051-1426
ISSN	2051-1426
DOI	10.1136/jitc-2019-000433
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Article ; Online: Tumor-infiltrating immune cells and prognosis: the potential link between conventional cancer therapy and immunity.

Jochems, Caroline / Schlom, Jeffrey

Experimental biology and medicine (Maywood, N.J.)

2011 Volume 236, Issue 5, Page(s) 567–579

Abstract: Numerous studies have now documented a link between the immune infiltrate in several human carcinoma types and prognosis and response to therapy. The most comprehensive of these studies were in colorectal cancer with similar conclusions by numerous ... ...

Abstract	Numerous studies have now documented a link between the immune infiltrate in several human carcinoma types and prognosis and response to therapy. The most comprehensive of these studies were in colorectal cancer with similar conclusions by numerous groups. Analyses of immune infiltrate of several other carcinoma types also showed general correlations between immune infiltrate and prognosis, but with some conflicting results. This review will attempt to summarize the current state of this field and point out what factors may be responsible for some of the conflicting findings. Nonetheless, the breadth of reports drawing similar conclusions for some cancer cell types leads one to more seriously consider the link between immune cell infiltrate and tumor prognosis and/or response to therapy, and the potential for combining conventional cancer therapy with active immunotherapy employing therapeutic cancer vaccines.
MeSH term(s)	Humans ; Immunity/immunology ; Lymphocytes, Tumor-Infiltrating/immunology ; Neoplasms/diagnosis ; Neoplasms/immunology ; Neoplasms/therapy ; Prognosis
Language	English
Publishing date	2011-04-12
Publishing country	Switzerland
Document type	Journal Article ; Research Support, N.I.H., Intramural ; Review
ZDB-ID	4015-0
ISSN	1535-3699 ; 1525-1373 ; 0037-9727
ISSN (online)	1535-3699 ; 1525-1373
ISSN	0037-9727
DOI	10.1258/ebm.2011.011007
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Article ; Online: An IL-15 superagonist/IL-15Rα fusion complex protects and rescues NK cell-cytotoxic function from TGF-β1-mediated immunosuppression.

Fujii, Rika / Jochems, Caroline / Tritsch, Sarah R / Wong, Hing C / Schlom, Jeffrey / Hodge, James W

Cancer immunology, immunotherapy : CII

2018 Volume 67, Issue 4, Page(s) 675–689

Abstract: Natural killer (NK) cells are innate cytotoxic lymphocytes that play a fundamental role in the immunosurveillance of cancers. NK cells of cancer patients exhibit impaired function mediated by immunosuppressive factors released from the tumor ... ...

Abstract	Natural killer (NK) cells are innate cytotoxic lymphocytes that play a fundamental role in the immunosurveillance of cancers. NK cells of cancer patients exhibit impaired function mediated by immunosuppressive factors released from the tumor microenvironment (TME), such as transforming growth factor (TGF)-β1. An interleukin (IL)-15 superagonist/IL-15 receptor α fusion complex (IL-15SA/IL-15RA; ALT-803) activates the IL-15 receptor on CD8 T cells and NK cells, and has shown significant anti-tumor activity in several in vivo studies. This in vitro study investigated the efficacy of IL-15SA/IL-15RA on TGF-β1-induced suppression of NK cell-cytotoxic function. IL-15SA/IL-15RA inhibited TGF-β1 from decreasing NK cell lysis of four of four tumor cell lines (H460, LNCap, MCF7, MDA-MB-231). IL-15SA/IL-15RA rescued healthy donor and cancer patient NK cell-cytotoxicity, which had previously been suppressed by culture with TGF-β1. TGF-β1 downregulated expression of NK cell-activating markers and cytotoxic granules, such as CD226, NKG2D, NKp30, granzyme B, and perforin. Smad2/3 signaling was responsible for this TGF-β1-induced downregulation of NK cell-activating markers and cytotoxic granules. IL-15SA/IL-15RA blocked Smad2/3-induced transcription, resulting in the rescue of NK cell-cytotoxic function from TGF-β1-induced suppression. These findings suggest that in addition to increasing NK cell function via promoting the IL-15 signaling pathway, IL-15SA/IL-15RA can function as an inhibitor of TGF-β1 signaling, providing a potential remedy for NK cell dysfunction in the immunosuppressive tumor microenvironment.
MeSH term(s)	Antibodies, Monoclonal/administration & dosage ; Antibody-Dependent Cell Cytotoxicity ; Cytotoxicity, Immunologic/immunology ; Humans ; Immunosuppression ; Interleukin-15/immunology ; Killer Cells, Natural/drug effects ; Killer Cells, Natural/immunology ; Lymphocyte Activation ; Neoplasms/immunology ; Neoplasms/therapy ; Receptors, Interleukin-15/immunology ; Recombinant Fusion Proteins/immunology ; Transforming Growth Factor beta1/pharmacology ; Tumor Cells, Cultured
Chemical Substances	Antibodies, Monoclonal ; IL15 protein, human ; IL15RA protein, human ; Interleukin-15 ; Receptors, Interleukin-15 ; Recombinant Fusion Proteins ; TGFB1 protein, human ; Transforming Growth Factor beta1
Language	English
Publishing date	2018-02-01
Publishing country	Germany
Document type	Journal Article
ZDB-ID	195342-4
ISSN	1432-0851 ; 0340-7004
ISSN (online)	1432-0851
ISSN	0340-7004
DOI	10.1007/s00262-018-2121-4
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Article ; Online: A Phase I Single-Arm Study of Biweekly NHS-IL12 in Patients With Metastatic Solid Tumors.

Gatti-Mays, Margaret E / Tschernia, Nicholas P / Strauss, Julius / Madan, Ravi A / Karzai, Fatima H / Bilusic, Marijo / Redman, Jason / Sater, Houssein Abdul / Floudas, Charalampos S / Toney, Nicole J / Donahue, Renee N / Jochems, Caroline / Marté, Jennifer L / Francis, Deneise / McMahon, Sheri / Lamping, Elizabeth / Cordes, Lisa / Schlom, Jeffrey / Gulley, James L

The oncologist

2023 Volume 28, Issue 4, Page(s) 364–e217

Abstract: Background: NHS-IL12 is a first-in-class, recombinant fusion protein composed of the human monoclonal antibody NHS76 (binds exposed DNA/histones at sites of intratumoral necrosis) fused to 2 IL-12 heterodimers. The maximum tolerated dose (MTD) and ... ...

Abstract	Background: NHS-IL12 is a first-in-class, recombinant fusion protein composed of the human monoclonal antibody NHS76 (binds exposed DNA/histones at sites of intratumoral necrosis) fused to 2 IL-12 heterodimers. The maximum tolerated dose (MTD) and recommended phase II dose (RP2D) of NHS-IL12 monotherapy given subcutaneously (SC) every 4 weeks was previously reported. The study was expanded to include a high-exposure cohort with NHS-IL12 SC every 2 weeks (q2w). Methods: This single-arm, phase I trial evaluated NHS-IL12 12 µg/kg SC q2w or 16.8µg/kg SC q2w in patients with metastatic solid tumors. The primary endpoint was safety. Results: Using a 3+3 design, 13 patients with advanced cancer were enrolled and 12 were dose-limiting toxicity (DLT) evaluable. There was 1 DLT (Grade 3 aspartate transaminase/alanine transaminase [AST/ALT] elevation). Other grade 3 toxicities included: flu-like symptoms 1/13 (8%), decreased absolute lymphocyte count (ALC) 1/13 (8%), decreased white blood cell count (WBC) 1/13 (8%), but most adverse events reported were low grade and self-limiting grade. Fifty percent of evaluable patients (6/12) experienced stable disease (SD) with 42% (5/12) developing progressive disease (PD) at the first restaging. Conclusion: Biweekly NHS-IL12 was well tolerated in this small phase I study. Additional studies incorporating NHS-IL12 with other immunomodulating agents are underway. (ClinicalTrials.gov Identifier: NCT01417546).
MeSH term(s)	Humans ; State Medicine ; Interleukin-12/therapeutic use ; Neoplasms/drug therapy ; Neoplasms/pathology ; Neoplasms, Second Primary ; Recombinant Fusion Proteins/therapeutic use
Chemical Substances	Interleukin-12 (187348-17-0) ; Recombinant Fusion Proteins
Language	English
Publishing date	2023-01-13
Publishing country	England
Document type	Clinical Trial, Phase I ; Journal Article ; Research Support, N.I.H., Intramural
ZDB-ID	1409038-7
ISSN	1549-490X ; 1083-7159
ISSN (online)	1549-490X
ISSN	1083-7159
DOI	10.1093/oncolo/oyac244
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Article ; Online: Characterization of recombinant gorilla adenovirus HPV therapeutic vaccine PRGN-2009.

Pellom, Samuel T / Smalley Rumfield, Claire / Morillon, Y Maurice / Roller, Nicholas / Poppe, Lisa K / Brough, Douglas E / Sabzevari, Helen / Schlom, Jeffrey / Jochems, Caroline

JCI insight

2021 Volume 6, Issue 7

Abstract: There are approximately 44,000 cases of human papillomavirus-associated (HPV-associated) cancer each year in the United States, most commonly caused by HPV types 16 and 18. Prophylactic vaccines successfully prevent healthy people from acquiring HPV ... ...

Abstract	There are approximately 44,000 cases of human papillomavirus-associated (HPV-associated) cancer each year in the United States, most commonly caused by HPV types 16 and 18. Prophylactic vaccines successfully prevent healthy people from acquiring HPV infections via HPV-specific antibodies. In order to treat established HPV-associated malignancies, however, new therapies are necessary. Multiple recombinant gorilla adenovirus HPV vaccine constructs were evaluated in NSG-β2m-/- peripheral blood mononuclear cell-humanized mice bearing SiHa, a human HPV16+ cervical tumor, and/or in the syngeneic HPV16+ TC-1 model. PRGN-2009 is a therapeutic gorilla adenovirus HPV vaccine containing multiple cytotoxic T cell epitopes of the viral oncoproteins HPV 16/18 E6 and E7, including T cell enhancer agonist epitopes. PRGN-2009 treatment reduced tumor volume and increased CD8+ and CD4+ T cells in the tumor microenvironment of humanized mice bearing the human cervical tumor SiHa. PRGN-2009 monotherapy in the syngeneic TC-1 model also reduced tumor volumes and weights, generated high levels of HPV16 E6-specific T cells, and increased multifunctional CD8+ and CD4+ T cells in the tumor microenvironment. These studies provide the first evaluation to our knowledge of a therapeutic gorilla adenovirus HPV vaccine, PRGN-2009, showing promising preclinical antitumor efficacy and induction of HPV-specific T cells, along with the rationale for its evaluation in clinical trials.
MeSH term(s)	Adenoviruses, Simian/genetics ; Animals ; CD8-Positive T-Lymphocytes ; Cancer Vaccines/genetics ; Cancer Vaccines/pharmacology ; Cell Line, Tumor ; Epitopes ; Female ; Human papillomavirus 16/immunology ; Humans ; Mice, Inbred C57BL ; Neutrophils ; Oncogene Proteins, Viral/immunology ; Papillomavirus Vaccines/genetics ; Papillomavirus Vaccines/pharmacology ; Repressor Proteins/immunology ; T-Lymphocytes/drug effects ; T-Lymphocytes/immunology ; Tumor Microenvironment/drug effects ; Uterine Cervical Neoplasms/drug therapy ; Uterine Cervical Neoplasms/immunology ; Uterine Cervical Neoplasms/virology ; Vaccines, Synthetic/genetics ; Vaccines, Synthetic/pharmacology ; Xenograft Model Antitumor Assays ; Mice
Chemical Substances	Cancer Vaccines ; E6 protein, Human papillomavirus type 16 ; Epitopes ; Oncogene Proteins, Viral ; Papillomavirus Vaccines ; Repressor Proteins ; Vaccines, Synthetic
Language	English
Publishing date	2021-04-08
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Intramural ; Research Support, Non-U.S. Gov't
ISSN	2379-3708
ISSN (online)	2379-3708
DOI	10.1172/jci.insight.141912
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