scholarly journals Virus-Based Immunotherapy of Glioblastoma

Cancers ◽  
2019 ◽  
Vol 11 (2) ◽  
pp. 186 ◽  
Author(s):  
Miika Martikainen ◽  
Magnus Essand
Keyword(s):  
Immune Responses ◽  
Oncolytic Virus ◽  
Early Stage ◽  
Primary Brain Tumor ◽  
Oncolytic Viruses ◽  
Preclinical Models ◽  
Adjuvant Effect ◽  
Cell Responses ◽  
Near Future ◽  
Stimulation Of

Glioblastoma (GBM) is the most common type of primary brain tumor in adults. Despite recent advances in cancer therapy, including the breakthrough of immunotherapy, the prognosis of GBM patients remains dismal. One of the new promising ways to therapeutically tackle the immunosuppressive GBM microenvironment is the use of engineered viruses that kill tumor cells via direct oncolysis and via stimulation of antitumor immune responses. In this review, we focus on recently published results of phase I/II clinical trials with different oncolytic viruses and the new interesting findings in preclinical models. From syngeneic preclinical GBM models, it seems evident that oncolytic virus-mediated destruction of GBM tissue coupled with strong adjuvant effect, provided by the robust stimulation of innate antiviral immune responses and adaptive anti-tumor T cell responses, can be harnessed as potent immunotherapy against GBM. Although clinical testing of oncolytic viruses against GBM is at an early stage, the promising results from these trials give hope for the effective treatment of GBM in the near future.

scholarly journals Acellular Pertussis Vaccines and Pertussis Resurgence: Revise or Replace?

mBio ◽  
2014 ◽  
Vol 5 (3) ◽  
Author(s):  
Clara Maria Ausiello ◽  
Antonio Cassone
Keyword(s):  
Immune Responses ◽  
Whooping Cough ◽  
Experimental Models ◽  
Adaptive Immune Responses ◽  
Content Type ◽  
Antigenic Composition ◽  
Cell Responses ◽  
Adaptive Immune ◽  
Antibody Levels ◽  
Stimulation Of

ABSTRACTThe resurgence of pertussis (whooping cough) in countries with high vaccination coverage is alarming and invites reconsideration of the use of current acellular pertussis (aP) vaccines, which have largely replaced the old, reactogenic, whole-cell pertussis (wP) vaccine. Some drawbacks of these vaccines in terms of limited antigenic composition and early waning of antibody levels could be anticipated by the results of in-trial or postlicensure human investigations of B- and T-cell responses in aP versus wP vaccine recipients or unvaccinated, infected children. Recent data in experimental models, including primates, suggest that generation of vaccines capable of a potent, though regulated, stimulation of innate immunity driving effective, persistent adaptive immune responses againstBordetella pertussisinfection should be privileged. Adjuvants that skew Th1/Th17 responses or new wP (detoxified or attenuated) vaccines should be explored. Nonetheless, the high merits of the current aP vaccines in persuading people to resume vaccination against pertussis should not be forgotten.

scholarly journals Rotavirus Inner Capsid VP6 Acts as an Adjuvant in Formulations with Particulate Antigens Only

Vaccines ◽  
2020 ◽  
Vol 8 (3) ◽  
pp. 365
Author(s):  
Suvi Heinimäki ◽  
Kirsi Tamminen ◽  
Vesa P. Hytönen ◽  
Maria Malm ◽  
Vesna Blazevic
Keyword(s):  
T Cell ◽  
Immune Responses ◽  
Influenza A ◽  
Matrix Protein ◽  
T Cell Responses ◽  
Extracellular Matrix Protein ◽  
Potential Candidate ◽  
Adjuvant Effect ◽  
Cell Responses ◽  
Mucosal Antibody

Novel adjuvants present a concern for adverse effects, generating a need for alternatives. Rotavirus inner capsid VP6 protein could be considered a potential candidate, due to its ability to self-assemble into highly immunogenic nanospheres and nanotubes. These nanostructures exhibit immunostimulatory properties, which resemble those of traditional adjuvants, promoting the uptake and immunogenicity of the co-administered antigens. We have previously elucidated an adjuvant effect of VP6 on co-delivered norovirus and coxsackievirus B1 virus-like particles, increasing humoral and cellular responses and sparing the dose of co-delivered antigens. This study explored an immunostimulatory effect of VP6 nanospheres on smaller antigens, P particles formed by protruding domain of a norovirus capsid protein and a short peptide, extracellular matrix protein (M2e) of influenza A virus. VP6 exhibited a notable improving impact on immune responses induced by P particles in immunized mice, including systemic and mucosal antibody and T cell responses. The adjuvant effect of VP6 nanospheres was comparable to the effect of alum, except for induction of superior mucosal and T cell responses when P particles were co-administered with VP6. However, unlike alum, VP6 did not influence M2e-specific immune responses, suggesting that the adjuvant effect of VP6 is dependent on the particulate nature of the co-administered antigen.

scholarly journals Advances and potential pitfalls of oncolytic viruses expressing immunomodulatory transgene therapy for malignant gliomas

2020 ◽  
Vol 11 (6) ◽  
Author(s):  
Qing Zhang ◽  
Fusheng Liu
Keyword(s):  
Immune Responses ◽  
Oncolytic Virus ◽  
Immune Cell ◽  
Hot Spot ◽  
Malignant Gliomas ◽  
Oncolytic Viruses ◽  
Potential Treatment ◽  
Normal Tissues ◽  
Clinical Benefits ◽  
Basic Studies

AbstractGlioblastoma (GBM) is an immunosuppressive, lethal brain tumor. Despite advances in molecular understanding and therapies, the clinical benefits have remained limited, and the life expectancy of patients with GBM has only been extended to ~15 months. Currently, genetically modified oncolytic viruses (OV) that express immunomodulatory transgenes constitute a research hot spot in the field of glioma treatment. An oncolytic virus is designed to selectively target, infect, and replicate in tumor cells while sparing normal tissues. Moreover, many studies have shown therapeutic advantages, and recent clinical trials have demonstrated the safety and efficacy of their usage. However, the therapeutic efficacy of oncolytic viruses alone is limited, while oncolytic viruses expressing immunomodulatory transgenes are more potent inducers of immunity and enhance immune cell-mediated antitumor immune responses in GBM. An increasing number of basic studies on oncolytic viruses encoding immunomodulatory transgene therapy for malignant gliomas have yielded beneficial outcomes. Oncolytic viruses that are armed with immunomodulatory transgenes remain promising as a therapy against malignant gliomas and will undoubtedly provide new insights into possible clinical uses or strategies. In this review, we summarize the research advances related to oncolytic viruses that express immunomodulatory transgenes, as well as potential treatment pitfalls in patients with malignant gliomas.

scholarly journals IMMUNE RESPONSES IN VITRO

1972 ◽  
Vol 135 (3) ◽  
pp. 675-697 ◽  
Author(s):  
Carl W. Pierce ◽  
Susan M. Solliday ◽  
Richard Asofsky
Keyword(s):  
Immune Responses ◽  
Suppressive Effect ◽  
Complete Suppression ◽  
Antigen Receptors ◽  
Cell Responses ◽  
Myeloma Proteins ◽  
Specific Receptors ◽  
Dose Dependent ◽  
Stimulation Of

The suppressive effects of monospecific goat anti-mouse globulins on primary immunoglobulin class-specific plaque-forming cell responses in mouse spleen cell cultures were investigated. Anti-µ suppressed responses in all immunoglobulin classes, whereas anti-γ1 and anti-γ2 suppressed the γ1 and γ2 responses but not γM or γA responses, and anti-γA suppressed only γA responses. The mechanism of action of the anti-µ was studied in detail because of its suppression of responses in all immunoglobulin classes. The anti-µ was specific for µ-chain determinants; its activity was dose dependent, but was not mediated by killing cells with surface µ-chain determinants. Free γM but not γG myeloma proteins in solution effectively competed with µ-bearing cells for the anti-µ. An excess of anti-µ was necessary in the cultures for 48 hr to insure complete suppression of 5-day responses. However, after removal of excess anti-µ at 48 hr, responses could be stimulated by newly added antigen in cultures where incubation was prolonged to 7 days. Anti-µ was most effective when added at the initiation of cultures and had no suppressive effect when added at 48 hr. Excess antigen did not effectively compete with anti-µ for antigen receptors. Precursors of antibody-forming cells were shown to be the cell population where the suppressive activity of anti-µ was mediated. The experiments suggest that anti-µ combines with µ-chain determinants in antigen-specific receptors on the surfaces of antibody-forming cell precursors, prevents effective stimulation by antigen and subsequent antibody production. To explain suppression of responses in all Ig classes by anti-µ, several models were proposed. It is not possible to determine from the data whether stimulation of precursor cells with γG or γA receptors requires concommitant stimulation of separate cells with only γM receptors, or whether cells bearing γM receptors are precommitted to or differentiate into cells capable of synthesis of other Ig classes, or whether receptors of γM and another Ig class are present on some virgin precursors or the second Ig receptor appears after antigenic stimulation.

scholarly journals Combining Oncolytic Viruses and Small Molecule Therapeutics: Mutual Benefits

Cancers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 3386
Author(s):  
Bart Spiesschaert ◽  
Katharina Angerer ◽  
John Park ◽  
Guido Wollmann
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Tumor Cells ◽  
Small Molecule ◽  
Antiviral Immunity ◽  
Oncolytic Viruses ◽  
Antitumor Immune Response ◽  
Antiviral Responses ◽  
Small Molecule Therapeutics ◽  
Immunosuppressive Factors

The focus of treating cancer with oncolytic viruses (OVs) has increasingly shifted towards achieving efficacy through the induction and augmentation of an antitumor immune response. However, innate antiviral responses can limit the activity of many OVs within the tumor and several immunosuppressive factors can hamper any subsequent antitumor immune responses. In recent decades, numerous small molecule compounds that either inhibit the immunosuppressive features of tumor cells or antagonize antiviral immunity have been developed and tested for. Here we comprehensively review small molecule compounds that can achieve therapeutic synergy with OVs. We also elaborate on the mechanisms by which these treatments elicit anti-tumor effects as monotherapies and how these complement OV treatment.

scholarly journals Prospects of immune checkpoint blockade and vaccine-based immunotherapy for glioblastoma

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Stefanie Tietze ◽  
Susanne Michen ◽  
Gabriele Schackert ◽  
Achim Temme
Keyword(s):  
Immune Checkpoint ◽  
Checkpoint Inhibitors ◽  
Primary Brain Tumor ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Blockade ◽  
Oncolytic Viruses ◽  
Therapeutic Vaccines ◽  
Dismal Prognosis ◽  
Tumor Parenchyma ◽  
Immunosuppressive Microenvironment

Abstract Glioblastoma multiforme (GBM) is the most prevalent primary brain tumor endowed with a dismal prognosis. Nowadays, immunotherapy in a particular immune checkpoint blockade and therapeutic vaccines are being extensively pursued. Yet, several characteristics of GBM may impact such immunotherapeutic approaches. This includes tumor heterogeneity, the relatively low mutational load of primary GBM, insufficient delivery of antibodies to tumor parenchyma and the unique immunosuppressive microenvironment of GBM. Moreover, standard treatment of GBM, comprising temozolomide chemotherapy, radiotherapy and in most instances the application of glucocorticoids for management of brain edema, results in a further increased immunosuppression. This review will provide a brief introduction to the principles of vaccine-based immunotherapy and give an overview of the current clinical studies, which employed immune checkpoint inhibitors, oncolytic viruses-based vaccination, cell-based and peptide-based vaccines. Recent experiences as well as the latest developments are reviewed. Overcoming obstacles, which limit the induction and long-term immune response against GBM when using vaccination approaches, are necessary for the implementation of effective immunotherapy of GBM.

scholarly journals Advances in Targeting Cutaneous Melanoma

Cancers ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 2090
Author(s):  
Dimitri Kasakovski ◽  
Marina Skrygan ◽  
Thilo Gambichler ◽  
Laura Susok
Keyword(s):  
Cutaneous Melanoma ◽  
Clinical Investigation ◽  
Early Stage ◽  
Treatment Options ◽  
Treatment Resistance ◽  
Immune Checkpoint Blockade ◽  
Oncolytic Viruses ◽  
Cancer Site ◽  
Western World ◽  
Pharmacological Agents

To date, the skin remains the most common cancer site among Caucasians in the western world. The complex, layered structure of human skin harbors a heterogenous population of specialized cells. Each cell type residing in the skin potentially gives rise to a variety of cancers, including non-melanoma skin cancer, sarcoma, and cutaneous melanoma. Cutaneous melanoma is known to exacerbate and metastasize if not detected at an early stage, with mutant melanomas tending to acquire treatment resistance over time. The intricacy of melanoma thus necessitates diverse and patient-centered targeted treatment options. In addition to classical treatment through surgical intervention and radio- or chemotherapy, several systemic and intratumoral immunomodulators, pharmacological agents (e.g., targeted therapies), and oncolytic viruses are trialed or have been recently approved. Moreover, utilizing combinations of immune checkpoint blockade with targeted, oncolytic, or anti-angiogenic approaches for patients with advanced disease progression are promising approaches currently under pre-clinical and clinical investigation. In this review, we summarize the current ‘state-of-the-art’ as well as discuss emerging agents and regimens in cutaneous melanoma treatment.

scholarly journals Experts’ opinion on the detection and management of prediabetes in Lebanon

2021 ◽  
Vol 104 (3) ◽  
pp. 003685042110294
Author(s):  
Emile Andari ◽  
Paola Atallah ◽  
Sami Azar ◽  
Akram Echtay ◽  
Selim Jambart ◽  
...  
Keyword(s):  
Risk Factors ◽  
Preliminary Report ◽  
Early Stage ◽  
National Guidelines ◽  
Lifestyle Modifications ◽  
Multiple Tests ◽  
Lebanese Population ◽  
To Come ◽  
Near Future

Given that the complications of type 2 diabetes can start at an early stage, early detection and appropriate management of prediabetes are essential. We aimed to develop an expert opinion on prediabetes in Lebanon to pave the way for national guidelines tailored for the Lebanese population in the near future. A panel of seven diabetes experts conducted a thorough literature review and discussed their opinions and experiences before coming up with a set of preliminary recommendations for the detection and management of prediabetes in Lebanon. Lebanese physicians employ multiple tests for the diagnosis of prediabetes and no national cut-off values exist. The panel agreed that prediabetes screening should be focused on patients exceeding 45 years of age with otherwise no risk factors and on adults with risk factors. The panel reached that fasting plasma glucose (FPG) and HbA1c should be used for prediabetes diagnosis in Lebanon. FPG values of 100–125 mg/dL or HbA1c values of 5.7%–6.4% were agreed upon as indicative of prediabetes. For the management of prediabetes, a three-step approach constituting lifestyle modifications, pharmacological treatment and bariatric surgery is recommended. There should be more focus on research on prediabetes in Lebanon. This preliminary report will be further discussed with the Lebanese Society of Endocrinology, Diabetes and Lipids in 2021 in order to come up with the first Lebanese national guidelines for the detection and management of prediabetes in Lebanon.

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