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Article: Expression of SARS-CoV-2-Related Surface Proteins in Non-Small-Cell Lung Cancer Patients and the Influence of Standard of Care Therapy.

Deben, Christophe / Le Compte, Maxim / Siozopoulou, Vasiliki / Lambrechts, Hilde / Hermans, Christophe / Lau, Ho Wa / Huizing, Manon / Lamote, Kevin / Hendriks, Jeroen M H / Van Dam, Peter / Pauwels, Patrick / Smits, Evelien L J / Peeters, Marc / Lardon, Filip

Cancers

2022 Volume 14, Issue 17

Abstract: ... membranous (m)ACE2 protein expression and soluble (s)ACE2 levels, with a particular focus on standard of care ...

Abstract	In this study, we aimed to study the expression of SARS-CoV-2-related surface proteins in non-small-cell lung cancer (NSCLC) cells and identify clinicopathological characteristics that are related to increased membranous (m)ACE2 protein expression and soluble (s)ACE2 levels, with a particular focus on standard of care (SOC) therapies. ACE2 (
Language	English
Publishing date	2022-08-23
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers14174074
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Article ; Online: Dendritic Cells as Vaccines: Key Regulators of Tolerance and Immunity.

Tel, Jurjen / Benitez-Ribas, Daniel / Janssen, Edith M / Smits, Evelien L J / Jacobs, Joannes F M

Mediators of inflammation

2016 Volume 2016, Page(s) 5789725

MeSH term(s)	Animals ; Dendritic Cells/immunology ; Humans ; Immunity/physiology ; Immunotherapy ; Vaccines/immunology
Chemical Substances	Vaccines
Language	English
Publishing date	2016
Publishing country	United States
Document type	Journal Article
ZDB-ID	1137605-3
ISSN	1466-1861 ; 0962-9351
ISSN (online)	1466-1861
ISSN	0962-9351
DOI	10.1155/2016/5789725
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Zs.A 3575: Show issues

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Article: The Search for an Interesting Partner to Combine with PD-L1 Blockade in Mesothelioma: Focus on TIM-3 and LAG-3.

Marcq, Elly / Van Audenaerde, Jonas R M / De Waele, Jorrit / Merlin, Céline / Pauwels, Patrick / van Meerbeeck, Jan P / Fisher, Scott A / Smits, Evelien L J

Cancers

2021 Volume 13, Issue 2

Abstract: Malignant pleural mesothelioma (MPM) is an aggressive cancer that is causally associated with previous asbestos exposure in most afflicted patients. The prognosis of patients remains dismal, with a median overall survival of only 9-12 months, due to the ... ...

Abstract	Malignant pleural mesothelioma (MPM) is an aggressive cancer that is causally associated with previous asbestos exposure in most afflicted patients. The prognosis of patients remains dismal, with a median overall survival of only 9-12 months, due to the limited effectiveness of any conventional anti-cancer treatment. New therapeutic strategies are needed to complement the limited armamentarium against MPM. We decided to focus on the combination of different immune checkpoint (IC) blocking antibodies (Abs). Programmed death-1 (PD-1), programmed death ligand-1 (PD-L1), T-cell immunoglobulin mucin-3 (TIM-3), and lymphocyte activation gene-3 (LAG-3) blocking Abs were tested as monotherapies, and as part of a combination strategy with a second IC inhibitor. We investigated their effect in vitro by examining the changes in the immune-related cytokine secretion profile of supernatant collected from treated allogeneic MPM-peripheral blood mononuclear cell (PBMC) co-cultures. Based on our in vitro results of cytokine secretion, and flow cytometry data that showed a significant upregulation of PD-L1 on PBMC after co-culture, we chose to further investigate the combinations of anti PD-L1 + anti TIM-3 versus anti PD-L1 + anti LAG-3 therapies in vivo in the AB1-HA BALB/cJ mesothelioma mouse model. PD-L1 monotherapy, as well as its combination with LAG-3 blockade, resulted in in-vivo delayed tumor growth and significant survival benefit.
Language	English
Publishing date	2021-01-14
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers13020282
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Article: Interferon α may be back on track to treat acute myeloid leukemia.

Smits, Evelien L J M / Anguille, Sébastien / Berneman, Zwi N

Oncoimmunology

2013 Volume 2, Issue 4, Page(s) e23619

Abstract: Our own experience and a thorough literature review suggest that interferon α (IFNα) should be reconsidered for the treatment of acute myeloid leukemia patients. Most likely, the success of such treatment depends on the achievement of high serum levels ... ...

Abstract	Our own experience and a thorough literature review suggest that interferon α (IFNα) should be reconsidered for the treatment of acute myeloid leukemia patients. Most likely, the success of such treatment depends on the achievement of high serum levels of IFNα for several months, which can be obtained by using pegylated IFNα.
Language	English
Publishing date	2013-04-07
Publishing country	United States
Document type	Journal Article
ZDB-ID	2645309-5
ISSN	2162-402X ; 2162-4011
ISSN (online)	2162-402X
ISSN	2162-4011
DOI	10.4161/onci.23619
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Article ; Online: A systematic review on poly(I:C) and poly-ICLC in glioblastoma: adjuvants coordinating the unlocking of immunotherapy.

De Waele, Jorrit / Verhezen, Tias / van der Heijden, Sanne / Berneman, Zwi N / Peeters, Marc / Lardon, Filip / Wouters, An / Smits, Evelien L J M

Journal of experimental & clinical cancer research : CR

2021 Volume 40, Issue 1, Page(s) 213

Abstract: Immunotherapy is currently under intensive investigation as a potential breakthrough treatment option for glioblastoma. Given the anatomical and immunological complexities surrounding glioblastoma, lymphocytes that infiltrate the brain to develop durable ...

Abstract	Immunotherapy is currently under intensive investigation as a potential breakthrough treatment option for glioblastoma. Given the anatomical and immunological complexities surrounding glioblastoma, lymphocytes that infiltrate the brain to develop durable immunity with memory will be key. Polyinosinic:polycytidylic acid, or poly(I:C), and its derivative poly-ICLC could serve as a priming or boosting therapy to unleash lymphocytes and other factors in the (immuno)therapeutic armory against glioblastoma. Here, we present a systematic review on the effects and efficacy of poly(I:C)/poly-ICLC for glioblastoma treatment, ranging from preclinical work on cellular and murine glioblastoma models to reported and ongoing clinical studies. MEDLINE was searched until 15 May 2021 to identify preclinical (glioblastoma cells, murine models) and clinical studies that investigated poly(I:C) or poly-ICLC in glioblastoma. A systematic review approach was conducted according to PRISMA guidelines. ClinicalTrials.gov was queried for ongoing clinical studies. Direct pro-tumorigenic effects of poly(I:C) on glioblastoma cells have not been described. On the contrary, poly(I:C) changes the immunological profile of glioblastoma cells and can also kill them directly. In murine glioblastoma models, poly(I:C) has shown therapeutic relevance as an adjuvant therapy to several treatment modalities, including vaccination and immune checkpoint blockade. Clinically, mostly as an adjuvant to dendritic cell or peptide vaccines, poly-ICLC has been demonstrated to be safe and capable of eliciting immunological activity to boost therapeutic responses. Poly-ICLC could be a valuable tool to enhance immunotherapeutic approaches for glioblastoma. We conclude by proposing several promising combination strategies that might advance glioblastoma immunotherapy and discuss key pre-clinical aspects to improve clinical translation.
MeSH term(s)	Animals ; Brain Neoplasms/drug therapy ; Brain Neoplasms/immunology ; Cancer Vaccines/therapeutic use ; Carboxymethylcellulose Sodium/analogs & derivatives ; Carboxymethylcellulose Sodium/therapeutic use ; Clinical Trials as Topic ; Glioblastoma/drug therapy ; Glioblastoma/immunology ; Humans ; Immune Checkpoint Inhibitors/therapeutic use ; Immunotherapy ; Mice ; Poly I-C/therapeutic use ; Polylysine/analogs & derivatives ; Polylysine/therapeutic use
Chemical Substances	Cancer Vaccines ; Immune Checkpoint Inhibitors ; Polylysine (25104-18-1) ; poly ICLC (7KYP9TKT70) ; Carboxymethylcellulose Sodium (K679OBS311) ; Poly I-C (O84C90HH2L)
Language	English
Publishing date	2021-06-25
Publishing country	England
Document type	Journal Article ; Review ; Systematic Review
ZDB-ID	803138-1
ISSN	1756-9966 ; 0392-9078
ISSN (online)	1756-9966
ISSN	0392-9078
DOI	10.1186/s13046-021-02017-2
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Zs.A 2065: Show issues

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Article ; Online: Humoral and Cellular Immune Responses against SARS-CoV-2 after Third Dose BNT162b2 following Double-Dose Vaccination with BNT162b2 versus ChAdOx1 in Patients with Cancer.

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

2022 Volume 29, Issue 3, Page(s) 635–646

Abstract: Purpose: Patients with cancer display reduced humoral responses after double-dose COVID-19 vaccination, whereas their cellular response is more comparable with that in healthy individuals. Recent studies demonstrated that a third vaccination dose boosts ...

Abstract	Purpose: Patients with cancer display reduced humoral responses after double-dose COVID-19 vaccination, whereas their cellular response is more comparable with that in healthy individuals. Recent studies demonstrated that a third vaccination dose boosts these immune responses, both in healthy people and patients with cancer. Because of the availability of many different COVID-19 vaccines, many people have been boosted with a different vaccine from the one used for double-dose vaccination. Data on such alternative vaccination schedules are scarce. This prospective study compares a third dose of BNT162b2 after double-dose BNT162b2 (homologous) versus ChAdOx1 (heterologous) vaccination in patients with cancer. Experimental design: A total of 442 subjects (315 patients and 127 healthy) received a third dose of BNT162b2 (230 homologous vs. 212 heterologous). Vaccine-induced adverse events (AE) were captured up to 7 days after vaccination. Humoral immunity was assessed by SARS-CoV-2 anti-S1 IgG antibody levels and SARS-CoV-2 50% neutralization titers (NT50) against Wuhan and BA.1 Omicron strains. Cellular immunity was examined by analyzing CD4+ and CD8+ T-cell responses against SARS-CoV-2-specific S1 and S2 peptides. Results: Local AEs were more common after heterologous boosting. SARS-CoV-2 anti-S1 IgG antibody levels did not differ significantly between homologous and heterologous boosted subjects [GMT 1,755.90 BAU/mL (95% CI, 1,276.95-2,414.48) vs. 1,495.82 BAU/mL (95% CI, 1,131.48-1,977.46)]. However, homologous-boosted subjects show significantly higher NT50 values against BA.1 Omicron. Subjects receiving heterologous boosting demonstrated increased spike-specific CD8+ T cells, including higher IFNγ and TNFα levels. Conclusions: In patients with cancer who received double-dose ChAdOx1, a third heterologous dose of BNT162b2 was able to close the gap in antibody response.
MeSH term(s)	Humans ; Antibodies, Viral ; BNT162 Vaccine ; COVID-19/prevention & control ; COVID-19 Vaccines ; Immunity, Cellular ; Immunoglobulin G ; Neoplasms/therapy ; Prospective Studies ; SARS-CoV-2 ; Vaccination
Chemical Substances	Antibodies, Viral ; BNT162 Vaccine ; COVID-19 Vaccines ; Immunoglobulin G
Language	English
Publishing date	2022-10-31
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1225457-5
ISSN	1557-3265 ; 1078-0432
ISSN (online)	1557-3265
ISSN	1078-0432
DOI	10.1158/1078-0432.CCR-22-2185
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Zs.A 4223: Show issues

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Article: Dendritic Cells and Programmed Death-1 Blockade: A Joint Venture to Combat Cancer.

Versteven, Maarten / Van den Bergh, Johan M J / Marcq, Elly / Smits, Evelien L J / Van Tendeloo, Viggo F I / Hobo, Willemijn / Lion, Eva

Frontiers in immunology

2018 Volume 9, Page(s) 394

Abstract: Two decades of clinical cancer research with dendritic cell (DC)-based vaccination have proved that this type of personalized medicine is safe and has the capacity to improve survival, but monotherapy is unlikely to cure the cancer. Designed to empower ... ...

Abstract	Two decades of clinical cancer research with dendritic cell (DC)-based vaccination have proved that this type of personalized medicine is safe and has the capacity to improve survival, but monotherapy is unlikely to cure the cancer. Designed to empower the patient's antitumor immunity, huge research efforts are set to improve the efficacy of next-generation DC vaccines and to find synergistic combinations with existing cancer therapies. Immune checkpoint approaches, aiming to breach immune suppression and evasion to reinforce antitumor immunity, have been a revelation in the immunotherapy field. Early success of therapeutic antibodies blocking the programmed death-1 (PD-1) pathway has sparked the development of novel inhibitors and combination therapies. Hence, merging immunoregulatory tumor-specific DC strategies with PD-1-targeted approaches is a promising path to explore. In this review, we focus on the role of PD-1-signaling in DC-mediated antitumor immunity. In the quest of exploiting the full potential of DC therapy, different strategies to leverage DC immunopotency by impeding PD-1-mediated immune regulation are discussed, including the most advanced research on targeted therapeutic antibodies, lessons learned from chemotherapy-induced immune activation, and more recent developments with soluble molecules and gene-silencing techniques. An overview of DC/PD-1 immunotherapy combinations that are currently under preclinical and clinical investigation substantiates the clinical potential of such combination strategies.
MeSH term(s)	Animals ; Antibodies, Monoclonal/therapeutic use ; Cancer Vaccines/immunology ; Combined Modality Therapy ; Dendritic Cells/immunology ; Dendritic Cells/transplantation ; Drug Evaluation, Preclinical ; Humans ; Immunotherapy/methods ; Neoplasms/immunology ; Neoplasms/therapy ; Programmed Cell Death 1 Receptor/immunology
Chemical Substances	Antibodies, Monoclonal ; Cancer Vaccines ; PDCD1 protein, human ; Programmed Cell Death 1 Receptor
Language	English
Publishing date	2018-03-01
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2606827-8
ISSN	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2018.00394
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Article ; Online: Natural killer cells and their therapeutic role in pancreatic cancer: A systematic review.

Van Audenaerde, Jonas R M / Roeyen, Geert / Darcy, Phillip K / Kershaw, Michael H / Peeters, M / Smits, Evelien L J

Pharmacology & therapeutics

2018 Volume 189, Page(s) 31–44

Abstract: Pancreatic cancer is among the three deadliest cancers worldwide with the lowest 5-year survival of all cancers. Despite all efforts, therapeutic improvements have barely been made over the last decade. Even recent highly promising targeted and ... ...

Abstract	Pancreatic cancer is among the three deadliest cancers worldwide with the lowest 5-year survival of all cancers. Despite all efforts, therapeutic improvements have barely been made over the last decade. Even recent highly promising targeted and immunotherapeutic approaches did not live up to their expectations. Therefore, other horizons have to be explored. Natural Killer (NK) cells are gaining more and more interest as a highly attractive target for cancer immunotherapies, both as pharmaceutical target and for cell therapies. In this systematic review we summarise the pathophysiological adaptions of NK cells in pancreatic cancer and highlight possible (future) therapeutic NK cell-related targets. Furthermore, an extensive overview of recent therapeutic approaches with an effect on NK cells is given, including cytokine-based, viro- and bacteriotherapy and cell therapy. We also discuss ongoing clinical trials that might influence NK cells. In conclusion, although several issues regarding NK cells in pancreatic cancer remain unsolved and need further investigation, extensive evidence is already provided that support NK cell oriented approaches in pancreatic cancer.
MeSH term(s)	Animals ; Cell- and Tissue-Based Therapy ; Humans ; Immunologic Factors/therapeutic use ; Killer Cells, Natural/immunology ; Pancreatic Neoplasms/immunology ; Pancreatic Neoplasms/therapy
Chemical Substances	Immunologic Factors
Language	English
Publishing date	2018-04-13
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Systematic Review
ZDB-ID	194735-7
ISSN	1879-016X ; 0163-7258
ISSN (online)	1879-016X
ISSN	0163-7258
DOI	10.1016/j.pharmthera.2018.04.003
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Zs.A 1183: Show issues

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Article ; Online: Interleukin-15: new kid on the block for antitumor combination therapy.

Van den Bergh, Johan M J / Van Tendeloo, Viggo F I / Smits, Evelien L J M

Cytokine & growth factor reviews

2015 Volume 26, Issue 1, Page(s) 15–24

Abstract: Interleukin (IL)-15 is one of the most promising molecules to be used in antitumor immune therapy, as it is able to stimulate the main killer cells of both the innate and adaptive immune system. Although this cytokine can be used as a stand-alone ... ...

Abstract	Interleukin (IL)-15 is one of the most promising molecules to be used in antitumor immune therapy, as it is able to stimulate the main killer cells of both the innate and adaptive immune system. Although this cytokine can be used as a stand-alone immunotherapeutic agent, IL-15 will probably be most efficient in combination with other strategies to overcome high tumor burden, immune suppression of the tumor microenvironment and/or the short half-life of IL-15. In this review, we will discuss the combination strategies with IL-15 that have been tested to date in different animal tumor models, which include chemotherapy, other immunostimulatory cytokines, targeted therapy, adoptive cell transfer and gene therapy. In addition, we give an overview of IL-15 combination therapies that are currently tested in clinical studies to treat patients with hematological or advanced solid tumors.
MeSH term(s)	Adoptive Transfer ; Animals ; Combined Modality Therapy ; Cytokines/therapeutic use ; Genetic Therapy ; Half-Life ; Hematologic Neoplasms/therapy ; Humans ; Immunotherapy ; Interleukin-15/therapeutic use ; Neoplasms/therapy
Chemical Substances	Cytokines ; Interleukin-15
Language	English
Publishing date	2015-02
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1330534-7
ISSN	1879-0305 ; 1359-6101
ISSN (online)	1879-0305
ISSN	1359-6101
DOI	10.1016/j.cytogfr.2014.09.001
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Zs.A 2653: Show issues

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Article ; Online: Interleukin-15 stimulates natural killer cell-mediated killing of both human pancreatic cancer and stellate cells.

Van Audenaerde, Jonas R M / De Waele, Jorrit / Marcq, Elly / Van Loenhout, Jinthe / Lion, Eva / Van den Bergh, Johan M J / Jesenofsky, Ralf / Masamune, Atsushi / Roeyen, Geert / Pauwels, Patrick / Lardon, Filip / Peeters, Marc / Smits, Evelien L J

Oncotarget

2017 Volume 8, Issue 34, Page(s) 56968–56979

Abstract: Pancreatic ductal adenocarcinoma (PDAC) is the ... ...

Abstract	Pancreatic ductal adenocarcinoma (PDAC) is the 4
Language	English
Publishing date	2017-08-22
Publishing country	United States
Document type	Journal Article
ZDB-ID	2560162-3
ISSN	1949-2553 ; 1949-2553
ISSN (online)	1949-2553
ISSN	1949-2553
DOI	10.18632/oncotarget.18185
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