A novel biologic platform elicits profound T cell costimulatory activity and antitumor immunity in mice

AbstractCombination immunotherapies utilizing complementary modalities that target distinct tumor attributes or immunosuppressive mechanisms, or engage different arms of the antitumor immune response, can elicit greater therapeutic efficacy than the component monotherapies. Increasing the number of agents included in a therapeutic cocktail can further increase efficacy, however, this approach poses numerous challenges for clinical translation. Here, a novel platform to simplify combination immunotherapy by covalently linking immunotherapeutic agonists to the costimulatory receptors CD134 and CD137 into a single heterodimeric drug, “OrthomAb”, is shown. This reagent not only retains costimulatory T cell activity, but also elicits unique T cell functions that are not programmed by either individual agonist, and preferentially expands effector T cells over Tregs. Finally, in an aggressive melanoma model OrthomAb elicits bett er therapeutic efficacy compared to the unlinked agonists. This demonstration that two drugs can be combined into one provides a framework for distilling complex combination drug cocktails into simpler delivery platforms.
Source: Cancer Immunology, Immunotherapy - Category: Cancer & Oncology Source Type: research

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Conditions:   Melanoma;   Non-Small Cell Lung Cancer Intervention:   Drug: Single Arm Sponsors:   Cytosite Biopharma Inc.;   Massachusetts General Hospital;   University of Alabama at Birmingham Not yet recruiting
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
Abstract The complexity of the immune response and diversity of targets challenges conventional conceptual frameworks used in selecting and monitoring treatment with immune check-point inhibitors. The limitations of anatomic imaging in assessing response have been recognized. Varying patterns of response have been recognized. These patterns have different implications for the continuation and duration of therapy. Evidence supporting the role of 18F-fluorodeoxyglucose Positron Emission Tomography/Computed Tomography as a prognostic biomarker and in characterizing response is presented. An added benefit of this appr...
Source: Clinical Lung Cancer - Category: Cancer & Oncology Authors: Tags: PET Clin Source Type: research
ConclusionsImmune checkpoint inhibition can trigger inflammation in virtually any organ in the body, leading to diverse clinical manifestations. To our knowledge, this is the first case report of eosinophilic enteritis due to ipilimumab plus nivolumab.
Source: Journal for Immunotherapy of Cancer - Category: Cancer & Oncology Source Type: research
ConclusionsAnalysis of the spatially constrained distribution of CD8+ and CD163+ cells, representative of the opposite circuits of antitumor vs protumor immunity, respectively, may assist in identifying melanoma patients with improved response and better outcome upon treatment with MAPK inhibitors. These data underline the role of endogenous immune microenvironment in predisposing metastatic melanoma patients to benefit from therapies targeting driver-oncogenic pathways.
Source: Journal for Immunotherapy of Cancer - Category: Cancer & Oncology Source Type: research
AbstractAlthough immune checkpoint inhibitors (ICIs) have transformed the treatment landscape for patients with many advanced malignancies, only 15 –60% of patients respond, leaving a broad swath of patients who do not derive benefit. Identifying biomarkers to optimally identify patients who will benefit from ICIs is a major research focus for the oncology community. Thus far, predictive biomarker research has focused on tumor signatures such as microsatellite instability, programmed death-ligand 1 (PD-L1) expression and tumor mutational burden; clinical biomarkers have been far less studied. One potential clinical b...
Source: Journal for Immunotherapy of Cancer - Category: Cancer & Oncology Source Type: research
This article is protected by copyright. All rights reserved. PMID: 31729751 [PubMed - as supplied by publisher]
Source: European Journal of Immunology - Category: Allergy & Immunology Authors: Tags: Eur J Immunol Source Type: research
We examined publication bias and excess significance bias. 63 articles corresponding to 247 meta-analyses were eligible. Nine meta-analyses were classified to have convincing evidence, and 75 were classified as suggestive evidence. The clinical benefit of immunotherapy was supported by convincing evidence in the following settings: anti-PD-1/PD-L1 monoclonal antibody (mAb) therapy for treating advanced melanoma and non-small cell lung cancer (NSCLC), the combination of rituximab and chemotherapy for treating chronic lymphocytic leukemia and B-cell non-Hodgkin’s lymphoma, adoptive cell immunotherapy for NSCLC, and...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
Domenico Mallardo, MD, Istituto Nazionale Tumori " Fondazione Pascale " in Naples, discusses results from his trial – designed to evaluate anti-CTLA4 agents in patients with melanoma who relapsed on treatment with ipilimumab (Yervoy), which was presented at the 34th Annual Meeting&Pre-Conference Programs of the Society for Immunotherapy of Cancer (SITC 2019).
Source: CancerNetwork - Category: Cancer & Oncology Authors: Source Type: news
AbstractImmune checkpoint blockers (ICB) have revolutionized cancer therapy. However, complete response is observed in a minority of patients and most patients develop immune-related adverse events (irAEs). These include colitis, which can be treated with anti-tumor necrosis factor (TNF) antibodies such as Infliximab. In a recent issue of the Journal for ImmunoTherapy of Cancer, Badran et al. reported that co-administering Infliximab together with ICB to five cancer patients prevents colitis recurrence, with four of them exhibiting overall disease stability. The basis for this treatment strategy stemmed from our pre-clinic...
Source: Journal for Immunotherapy of Cancer - Category: Cancer & Oncology Source Type: research
ConclusionsThe tolerability of the combined checkpoint blockade in UM may possibly be better than in trials on cutaneous melanoma. This study implies that combined checkpoint blockade represents the hitherto most effective treatment option available for metastatic UM available outside of clinical trials.
Source: Journal for Immunotherapy of Cancer - Category: Cancer & Oncology Source Type: research
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