Multiple modulatory activities of Andrographis paniculata on immune responses and xenograft growth in esophageal cancer preclinical models

Phytomedicine ◽  
2019 ◽  
Vol 60 ◽  
pp. 152886 ◽  
Author(s):  
Grace Gar-Lee Yue ◽  
Lin Li ◽  
Julia Kin-Ming Lee ◽  
Hin-Fai Kwok ◽  
Eric Chun-Wai Wong ◽  
...  
Keyword(s):  
Esophageal Cancer ◽  
Immune Responses ◽  
Andrographis Paniculata ◽  
Preclinical Models ◽  
Xenograft Growth

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.

Autologous tumor lysate-pulsed dendritic cell vaccination therapy after resection of stage IIA (T2N0, T3N0) esophageal cancer: An analysis of immunological responses.

2018 ◽  
Vol 36 (5_suppl) ◽  
pp. 96-96
Author(s):  
Yasuyoshi Sato ◽  
Koichi Yagi ◽  
Kazuhiko Mori ◽  
Hirokazu Matsushita ◽  
Kazuhiro Kakimi ◽  
...  
Keyword(s):  
Esophageal Cancer ◽  
Dendritic Cell ◽  
Immune Responses ◽  
R0 Resection ◽  
Dendritic Cell Vaccination ◽  
Autologous Tumor ◽  
Tumor Lysate ◽  
Binding Prediction ◽  
Dc Vaccines ◽  
Vaccination Therapy

96 Background: Immunotherapy using active immunization of tumor associated antigens has been expected to improve the prognosis of malignant tumor patients. We conducted phase I trial to investigate safety and efficacy of autologous tumor lysate-pulsed dendritic cell (DC) vaccination therapy after resection for esophageal cancer. We already reported the clinical results for enrolled 11 patients. All patients completed the protocol therapy and no treatment-related adverse events more than grade 3 was observed (primary endpoint), and recurrence rate within 2 years was 18% (n = 2). In this study, we further analyzed the immune responses in vaccinated patients. Methods: Patients with stage IIA (T2N0 or T3N0, UICC TNM classification 6th edition) esophageal cancer after curative (R0) resection were eligible. Tumor lysate we used for DC vaccines potentially contains mutated proteins (neoantigens) derived from somatic mutations. Patients received DC vaccines (more than 5.0×106 cells) 6 times every 2 weeks. We evaluated neutrophil-to-lymphocyte ratio (NLR) in each patient from CRF data. We identified candidate neoantigens by next generation sequencing and MHC class I binding prediction algorism. We screened the immune responses against those neoantigens using HLA transgenic mice and healthy human PBMCs. Results: Absolute lymphocyte counts, absolute neutrophil counts and NLR were not specifically different between patients with or without recurrence. For specific immune responses, we observed the reactivity in 6 out of 59 candidate neoepitopes identified from two patients in HLA transgenic mouse system. Two out of 6 peptides displayed reactivity in human healthy PBMCs. Conclusions: We analyzed immune responses to predicted candidate neoantigens. We are now investigating immune landscape in the tumor using RNA sequencing data and its relevance to the antigen responses. Clinical trial information: UMIN000002837.

scholarly journals Molecular Repolarisation of Tumour-Associated Macrophages

Molecules ◽  
2018 ◽  
Vol 24 (1) ◽  
pp. 9 ◽  
Author(s):  
Floris van Dalen ◽  
Marleen van Stevendaal ◽  
Felix Fennemann ◽  
Martijn Verdoes ◽  
Olga Ilina
Keyword(s):  
Immune Responses ◽  
Immune Cells ◽  
Growth And Development ◽  
Tumour Microenvironment ◽  
Environmental Cues ◽  
Preclinical Models ◽  
Beneficial Effects ◽  
Macrophage Depletion ◽  
Cytotoxic Effector ◽  
Tumour Proliferation

The tumour microenvironment (TME) is composed of extracellular matrix and non-mutated cells supporting tumour growth and development. Tumour-associated macrophages (TAMs) are among the most abundant immune cells in the TME and are responsible for the onset of a smouldering inflammation. TAMs play a pivotal role in oncogenic processes as tumour proliferation, angiogenesis and metastasis, and they provide a barrier against the cytotoxic effector function of T lymphocytes and natural killer (NK) cells. However, TAMs are highly plastic cells that can adopt either pro- or anti-inflammatory roles in response to environmental cues. Consequently, TAMs represent an attractive target to recalibrate immune responses in the TME. Initial TAM-targeted strategies, such as macrophage depletion or disruption of TAM recruitment, have shown beneficial effects in preclinical models and clinical trials. Alternatively, reprogramming TAMs towards a proinflammatory and tumouricidal phenotype has become an attractive strategy in immunotherapy. This work summarises the molecular wheelwork of macrophage biology and presents an overview of molecular strategies to repolarise TAMs in immunotherapy.

scholarly journals Targeting the MHC Ligandome by Use of TCR-Like Antibodies

Antibodies ◽  
2019 ◽  
Vol 8 (2) ◽  
pp. 32 ◽  
Author(s):  
Lene Støkken Høydahl ◽  
Rahel Frick ◽  
Inger Sandlie ◽  
Geir Åge Løset
Keyword(s):  
Immune Responses ◽  
High Specificity ◽  
Infectious Agents ◽  
Presentation Of Self ◽  
Peptide Fragments ◽  
Preclinical Models ◽  
Mhc Molecules ◽  
Health And Disease ◽  
Targeting Peptide ◽  
Subsequent Activation

Monoclonal antibodies (mAbs) are valuable as research reagents, in diagnosis and in therapy. Their high specificity, the ease in production, favorable biophysical properties and the opportunity to engineer different properties make mAbs a versatile class of biologics. mAbs targeting peptide–major histocompatibility molecule (pMHC) complexes are often referred to as “TCR-like” mAbs, as pMHC complexes are generally recognized by T-cell receptors (TCRs). Presentation of self- and non-self-derived peptide fragments on MHC molecules and subsequent activation of T cells dictate immune responses in health and disease. This includes responses to infectious agents or cancer but also aberrant responses against harmless self-peptides in autoimmune diseases. The ability of TCR-like mAbs to target specific peptides presented on MHC allows for their use to study peptide presentation or for diagnosis and therapy. This extends the scope of conventional mAbs, which are generally limited to cell-surface or soluble antigens. Herein, we review the strategies used to generate TCR-like mAbs and provide a structural comparison with the analogous TCR in pMHC binding. We further discuss their applications as research tools and therapeutic reagents in preclinical models as well as challenges and limitations associated with their use.

A small-molecule SUMOylation inhibitor activates antitumor immune responses and potentiates immune therapies in preclinical models

2021 ◽  
Vol 13 (611) ◽  
Author(s):  
Eric S. Lightcap ◽  
Pengfei Yu ◽  
Stephen Grossman ◽  
Keli Song ◽  
Mithun Khattar ◽  
...  
Keyword(s):  
Immune Responses ◽  
Small Molecule ◽  
Preclinical Models ◽  
Immune Therapies

scholarly journals The adjuvant value of Andrographis paniculata in metastatic esophageal cancer treatment – from preclinical perspectives

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Lin Li ◽  
Grace Gar-Lee Yue ◽  
Julia Kin-Ming Lee ◽  
Eric Chun-Wai Wong ◽  
Kwok-Pui Fung ◽  
...  
Keyword(s):  
Esophageal Cancer ◽  
Cancer Treatment ◽  
Andrographis Paniculata

The anti-metastatic activity of a chinese herb Andrographis paniculata in esophageal cancer - a preclinical study

Planta Medica ◽  
2012 ◽  
Vol 78 (11) ◽  
Author(s):  
GGL Yue ◽  
JKM Lee ◽  
JYW Chan ◽  
K Pui Fung ◽  
PWY Chiu ◽  
...  
Keyword(s):  
Esophageal Cancer ◽  
Chinese Herb ◽  
Preclinical Study ◽  
Andrographis Paniculata ◽  
Metastatic Activity

scholarly journals Optimized polyepitope neoantigen DNA vaccines elicit neoantigen-specific immune responses in preclinical models and in clinical translation

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Lijin Li ◽  
Xiuli Zhang ◽  
Xiaoli Wang ◽  
Samuel W. Kim ◽  
John M. Herndon ◽  
...  
Keyword(s):  
Immune Responses ◽  
Neuroendocrine Tumor ◽  
Dna Vaccine ◽  
Dna Vaccines ◽  
Pancreatic Neuroendocrine Tumor ◽  
Clinical Translation ◽  
Mutant Form ◽  
Preclinical Models ◽  
Vaccine Platform

Abstract Background Preclinical studies and early clinical trials have shown that targeting cancer neoantigens is a promising approach towards the development of personalized cancer immunotherapies. DNA vaccines can be rapidly and efficiently manufactured and can integrate multiple neoantigens simultaneously. We therefore sought to optimize the design of polyepitope DNA vaccines and test optimized polyepitope neoantigen DNA vaccines in preclinical models and in clinical translation. Methods We developed and optimized a DNA vaccine platform to target multiple neoantigens. The polyepitope DNA vaccine platform was first optimized using model antigens in vitro and in vivo. We then identified neoantigens in preclinical breast cancer models through genome sequencing and in silico neoantigen prediction pipelines. Optimized polyepitope neoantigen DNA vaccines specific for the murine breast tumor E0771 and 4T1 were designed and their immunogenicity was tested in vivo. We also tested an optimized polyepitope neoantigen DNA vaccine in a patient with metastatic pancreatic neuroendocrine tumor. Results Our data support an optimized polyepitope neoantigen DNA vaccine design encoding long (≥20-mer) epitopes with a mutant form of ubiquitin (Ubmut) fused to the N-terminus for antigen processing and presentation. Optimized polyepitope neoantigen DNA vaccines were immunogenic and generated robust neoantigen-specific immune responses in mice. The magnitude of immune responses generated by optimized polyepitope neoantigen DNA vaccines was similar to that of synthetic long peptide vaccines specific for the same neoantigens. When combined with immune checkpoint blockade therapy, optimized polyepitope neoantigen DNA vaccines were capable of inducing antitumor immunity in preclinical models. Immune monitoring data suggest that optimized polyepitope neoantigen DNA vaccines are capable of inducing neoantigen-specific T cell responses in a patient with metastatic pancreatic neuroendocrine tumor. Conclusions We have developed and optimized a novel polyepitope neoantigen DNA vaccine platform that can target multiple neoantigens and induce antitumor immune responses in preclinical models and neoantigen-specific responses in clinical translation.

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