scholarly journals Antitumor Peptide-Based Vaccine in the Limelight

Vaccines ◽  
2022 ◽  
Vol 10 (1) ◽  
pp. 70
Author(s):  
Takumi Kumai ◽  
Hidekiyo Yamaki ◽  
Michihisa Kono ◽  
Ryusuke Hayashi ◽  
Risa Wakisaka ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Immune Cells ◽  
Immune Checkpoint ◽  
Tumor Antigens ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Blockade ◽  
Recent Experimental Data ◽  
Proof Of Concept ◽  
Cell Responses ◽  
Tumor Reduction

The success of the immune checkpoint blockade has provided a proof of concept that immune cells are capable of attacking tumors in the clinic. However, clinical benefit is only observed in less than 20% of the patients due to the non-specific activation of immune cells by the immune checkpoint blockade. Developing tumor-specific immune responses is a challenging task that can be achieved by targeting tumor antigens to generate tumor-specific T-cell responses. The recent advancements in peptide-based immunotherapy have encouraged clinicians and patients who are struggling with cancer that is otherwise non-treatable with current therapeutics. By selecting appropriate epitopes from tumor antigens with suitable adjuvants, peptides can elicit robust antitumor responses in both mice and humans. Although recent experimental data and clinical trials suggest the potency of tumor reduction by peptide-based vaccines, earlier clinical trials based on the inadequate hypothesis have misled that peptide vaccines are not efficient in eliminating tumor cells. In this review, we highlighted the recent evidence that supports the rationale of peptide-based antitumor vaccines. We also discussed the strategies to select the optimal epitope for vaccines and the mechanism of how adjuvants increase the efficacy of this promising approach to treat cancer.

scholarly journals A TLR4 agonist improves immune checkpoint blockade treatment by increasing the ratio of effector to regulatory cells within the tumor microenvironment

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
A. Farias ◽  
A. Soto ◽  
F. Puttur ◽  
C. J. Goldin ◽  
S. Sosa ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Tumor Growth ◽  
Therapeutic Effect ◽  
Immune Cells ◽  
Immune Checkpoint ◽  
Combined Treatment ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Blockade ◽  
Regulatory Cells ◽  
Ifn Γ

AbstractBrucella lumazine synthase (BLS) is a homodecameric protein that activates dendritic cells via toll like receptor 4, inducing the secretion of pro-inflammatory cytokines and chemokines. We have previously shown that BLS has a therapeutic effect in B16 melanoma-bearing mice only when administered at early stages of tumor growth. In this work, we study the mechanisms underlying the therapeutic effect of BLS, by analyzing the tumor microenvironment. Administration of BLS at early stages of tumor growth induces high levels of serum IFN-γ, as well as an increment of hematopoietic immune cells within the tumor. Moreover, BLS-treatment increases the ratio of effector to regulatory cells. However, all treated mice eventually succumb to the tumors. Therefore, we combined BLS administration with anti-PD-1 treatment. Combined treatment increases the outcome of both monotherapies. In conclusion, we show that the absence of the therapeutic effect at late stages of tumor growth correlates with low levels of serum IFN-γ and lower infiltration of immune cells in the tumor, both of which are essential to delay tumor growth. Furthermore, the combined treatment of BLS and PD-1 blockade shows that BLS could be exploited as an essential immunomodulator in combination therapy with an immune checkpoint blockade to treat skin cancer.

scholarly journals Targeting Metabolism to Control Immune Responses in Cancer and Improve Checkpoint Blockade Immunotherapy

Cancers ◽  
2021 ◽  
Vol 13 (23) ◽  
pp. 5912
Author(s):  
Angèle Luby ◽  
Marie-Clotilde Alves-Guerra
Keyword(s):  
Cancer Immunotherapy ◽  
Immune Cells ◽  
Immune Checkpoint ◽  
Metabolic Pathways ◽  
Cancer Metabolism ◽  
Metabolic Stress ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Blockade ◽  
New Therapeutic Approaches ◽  
Immunosuppressive Tumor Microenvironment

Over the past decade, advances in cancer immunotherapy through PD1–PDL1 and CTLA4 immune checkpoint blockade have revolutionized the management of cancer treatment. However, these treatments are inefficient for many cancers, and unfortunately, few patients respond to these treatments. Indeed, altered metabolic pathways in the tumor play a pivotal role in tumor growth and immune response. Thus, the immunosuppressive tumor microenvironment (TME) reprograms the behavior of immune cells by altering their cellular machinery and nutrient availability to limit antitumor functions. Today, thanks to a better understanding of cancer metabolism, immunometabolism and immune checkpoint evasion, the development of new therapeutic approaches targeting the energy metabolism of cancer or immune cells greatly improve the efficacy of immunotherapy in different cancer models. Herein, we highlight the changes in metabolic pathways that regulate the differentiation of pro- and antitumor immune cells and how TME-induced metabolic stress impedes their antitumor activity. Finally, we propose some drug strategies to target these pathways in the context of cancer immunotherapy.

scholarly journals Endocrine-related adverse events following ipilimumab in patients with advanced melanoma: a comprehensive retrospective review from a single institution

2014 ◽  
Vol 21 (2) ◽  
pp. 371-381 ◽  
Author(s):  
Mabel Ryder ◽  
Margaret Callahan ◽  
Michael A Postow ◽  
Jedd Wolchok ◽  
James A Fagin
Keyword(s):  
Clinical Trials ◽  
Adverse Events ◽  
Immune Checkpoint ◽  
Cytotoxic T Lymphocyte ◽  
Hormone Replacement ◽  
Symptomatic Relief ◽  
Hormone Secretion ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Blockade ◽  
Increased Risk

Novel immune checkpoint blockade with ipilimumab, an antibody blocking the cytotoxic T-lymphocyte antigen 4 (CTLA4), is revolutionizing cancer therapy. However, ipilimumab induces symptomatic, sometimes severe, endocrine immune-related adverse events (irAEs) that are inconsistently recognized and reported. The objective of this review was to comprehensively characterize the incidence, presentation, and management of endocrinopathies following ipilimumab therapy in a single center that is highly specialized in immune checkpoint blockade. We carried out a retrospective analysis of endocrine irAEs in melanoma patients receiving ipilimumab therapy in clinical trials between 2007 and 2013. A total of 256 patients were included in this analysis. We reviewed pituitary-, thyroid-, and adrenal-related hormone test results, as well as radiographic studies and the clinical histories of patients, to identify and characterize cases of hypophysitis, hypothyroidism, thyroiditis, and adrenal dysfunction. Following ipilimumab therapy, the overall incidence of hypophysitis was 8% and that of hypothyroidism/thyroiditis 6%. Primary adrenal dysfunction was rare. Therapy with a combination of ipilimumab and nivolumab, an anti-programmed cell death 1 (PDCD1, also called PD1) receptor antibody, was associated with a 22% incidence of either thyroiditis or hypothyroidism and a 9% incidence of hypophysitis. Symptomatic relief, in particular, for hypophysitis, was achieved in all patients with hormone replacement, although endogenous hormone secretion rarely recovered. In summary, we observed that CTLA4 blockade alone, and in particular in combination with PD1 blockade, is associated with an increased risk of symptomatic, sometimes severe, hypophysitis as well as thyroid dysfunction. Prompt initiation with hormone replacement reverses symptoms. Evaluation and reporting of endocrine irAEs in clinical trials should be done using standardized diagnostic criteria and terminology.

scholarly journals Beyond Ipilimumab: a review of immunotherapeutic approaches in clinical trials in Melanoma

2020 ◽  
Author(s):  
Gary Middleton
Keyword(s):  
Clinical Trials ◽  
Monoclonal Antibodies ◽  
Combination Therapy ◽  
Phase I ◽  
Immune Checkpoint ◽  
Standard Of Care ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Blockade ◽  
Novel Agents ◽  
Randomised Trials

Abstract In this first in a series of ‘Trials Watch’ articles we briefly review a highly selected set of clinical trials that are currently recruiting or about to open to recruitment in melanoma, the disease first transformed by the introduction of immune checkpoint blockade inhibitors (ICI). We place equal emphasis on phase I/II studies investigating the activity of biologically compelling novel immunotherapeutics, and on randomised trials of ICI with and without novel agents, as these latter studies optimise the standard of care use of ICI, and determine whether novel agents become part of the approved therapeutic armamentarium. We do not consider here combination therapy with other checkpoint antagonists or agonists besides combination of anti-PD-1/PD-L1 monoclonal antibodies (mAbs) with anti-CTLA4 mAbs, as these will be reviewed in a subsequent article in this series. A glossary of agents to be discussed is found at the end of this article.

scholarly journals CCL17/CCL22 Predict the Survival and Response to Immune Checkpoint Blockade Therapy of Patients with HNSCC

2021 ◽  
Author(s):  
Wenkai Zhou ◽  
Xu Zhang ◽  
Yin Long ◽  
Xiaohu Lin ◽  
Yu Zhang ◽  
...  
Keyword(s):  
T Cells ◽  
Immune Cells ◽  
Immune Checkpoint ◽  
Predictive Biomarker ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Blockade ◽  
High Expression ◽  
New Strategy ◽  
And Function ◽  
Collaborative Activities

Abstract Background: Head and neck squamous cell carcinoma (HNSCC) was considered as an immunosuppressive disease. Cross-talk between cancer cells and immune cells is modulated in part by chemokines CC ligands (CCL). However, the prognostic value and function of CCL in HNSCC have not been clarified. Methods: To identify the key members of CCL family, CCL17 and CCL22 were selected through co-expression analysis. We further evaluated the correlation between the expression of CCL17/CCL22 and cancer immune infiltration through TIMER and scRNA-seq data. TIDE database was used to evaluate whether these molecules can be used as targets for immunotherapy.Results: The results indicated high expression of CCL17 and CCL22 were associated with a better prognosis. CCL17/CCL22 might regulate the T cells activation and were positively correlated with the CD4+ T cells infiltration levels. CCL17/CCL22 can also act as a predictive biomarker for the response to immune checkpoint blockade in HNSCC patients.Conclusions: High expression of CCL17/CCL22 may predict a better response of immune checkpoint blockade therapy in HNSCC. These findings may elucidate the roles played by CCL17/CCL22 in HNSCC progression and identify a new strategy in promoting collaborative activities in the context of immunotherapy.

scholarly journals Synergy between Toxoplasma gondii type I ΔGRA17 immunotherapy and PD-L1 checkpoint inhibition triggers the regression of targeted and distal tumors

2021 ◽  
Vol 9 (11) ◽  
pp. e002970
Author(s):  
Yu-Chao Zhu ◽  
Hany M Elsheikha ◽  
Jian-Hua Wang ◽  
Shuai Fang ◽  
Jun-Jun He ◽  
...  
Keyword(s):  
Immune Response ◽  
Toxoplasma Gondii ◽  
Tumor Growth ◽  
Immune Cells ◽  
Immune Checkpoint ◽  
Immune Cell ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Blockade ◽  
Complete Regression ◽  
Type I

BackgroundIn this study, we hypothesize that the ability of the protozoan Toxoplasma gondii to modulate immune response within the tumor might improve the therapeutic effect of immune checkpoint blockade. We examined the synergetic therapeutic activity of attenuated T. gondii RH ΔGRA17 strain and programmed death ligand-1 (PD-L1) treatment on both targeted and distal tumors in mice.MethodsThe effects of administration of T. gondii RH ΔGRA17 strain on the tumor volume and survival rate of mice bearing flank B16-F10, MC38, or LLC tumors were studied. We characterized the effects of ΔGRA17 on tumor biomarkers’ expression, PD-L1 expression, immune cells infiltrating the tumors, and expression of immune-related genes by using immunohistochemistry, immunofluorescence, flow cytometry, NanoString platform, and real-time quantitative PCR, respectively. The role of immune cells in the efficacy of ΔGRA17 plus PD-L1 blockade therapy was determined via depletion of immune cell subtypes.ResultsTreatment with T. gondii ΔGRA17 tachyzoites and anti-PD-L1 therapy significantly extended the survival of mice and suppressed tumor growth in preclinical mouse models of melanoma, Lewis lung carcinoma, and colon adenocarcinoma. Attenuation of the tumor growth was detected in the injected and distant tumors, which was associated with upregulation of innate and adaptive immune pathways. Complete regression of tumors was underpinned by late interferon-gamma-producing CD8+ cytotoxic T cells.ConclusionThe results from these models indicate that intratumoral injection of ΔGRA17 induced a systemic effect, improved mouse immune response, and sensitized immunologically ‘cold’ tumors and rendered them sensitive to immune checkpoint blockade therapy.

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