Related Papers
Journal for ImmunoTherapy of Cancer
BT7480, a novel fully synthetic Bicycle tumor-targeted immune cell agonist™ (Bicycle TICA™) induces tumor localized CD137 agonism
2021 •
Drasti Kanakia
BackgroundCD137 (4-1BB) is an immune costimulatory receptor with high therapeutic potential in cancer. We are creating tumor target-dependent CD137 agonists using a novel chemical approach based on fully synthetic constrained bicyclic peptide (Bicycle®) technology. Nectin-4 is overexpressed in multiple human cancers that may benefit from CD137 agonism. To this end, we have developed BT7480, a novel, first-in-class, Nectin-4/CD137 Bicycle tumor-targeted immune cell agonist™ (Bicycle TICA™).MethodsNectin-4 and CD137 co-expression analyses in primary human cancer samples was performed. Chemical conjugation of two CD137 Bicycles to a Nectin-4 Bicycle led to BT7480, which was then evaluated using a suite of in vitro and in vivo assays to characterize its pharmacology and mechanism of action.ResultsTranscriptional profiling revealed that Nectin-4 and CD137 were co-expressed in a variety of human cancers with high unmet need and spatial proteomic imaging found CD137-expressing immune cells...
Clinical Cancer Research
Boosting Cancer Immunotherapy with Anti-CD137 Antibody Therapy
2015 •
Cariad Chester
Tumor antigen-targeting monoclonal antibody-based immunotherapy: Orchestrating combined strategies for the development of long-term antitumor immunity
Henri-Alexandre MICHAUD, Nathalie Bonnefoy
Current Drug Targets
Targeted Cancer Immunotherapy Using Ligands of the Tumor Necrosis Factor Super-Family
2009 •
Wijnand Helfrich
Oncoimmunology
Trial Watch: Immunomodulatory monoclonal antibodies for oncological indications
2015 •
Jérôme Galon
Immunomodulatory monoclonal antibodies (mAbs) differ from their tumor-targeting counterparts because they exert therapeutic effects by directly interacting with soluble or (most often) cellular components of the immune system. Besides holding promise for the treatment of autoimmune and inflammatory disorders, immunomodulatory mAbs have recently been shown to constitute a potent therapeutic weapon against neoplastic conditions. One class of immunomodulatory mAbs operates by inhibiting safeguard systems that are frequently harnessed by cancer cells to establish immunological tolerance, the so-called "immune checkpoints." No less than 3 checkpoint-blocking mAbs have been approved worldwide for use in oncological indications, 2 of which during the past 12 months. These molecules not only mediate single-agent clinical activity in patients affected by specific neoplasms, but also significantly boost the efficacy of several anticancer chemo-, radio- or immunotherapies. Here, we s...
Oncoimmunology
Trial Watch: Immunostimulatory monoclonal antibodies in cancer therapy
2014 •
Alexander Eggermont, Jérôme Galon
Immunostimulatory monoclonal antibodies (mAbs) exert antineoplastic effects by eliciting a novel or reinstating a pre-existing antitumor immune response. Most often, immunostimulatory mAbs activate T lymphocytes or natural killer (NK) cells by inhibiting immunosuppressive receptors, such as cytotoxic T lymphocyte-associated protein 4 (CTLA4) or programmed cell death 1 (PDCD1, best known as PD-1), or by engaging co-stimulatory receptors, like CD40, tumor necrosis factor receptor superfamily, member 4 (TNFRSF4, best known as OX40) or TNFRSF18 (best known as GITR). The CTLA4-targeting mAb ipilimumab has been approved by the US Food and Drug Administration for use in patients with unresectable or metastatic melanoma in 2011. The therapeutic profile of ipilimumab other CTLA4-blocking mAbs, such as tremelimumab, is currently being assessed in subjects affected by a large panel of solid neoplasms. In the last few years, promising clinical results have also been obtained with nivolumab, a P...
Antibody Therapeutics
Next-generation cytokines for cancer immunotherapy
diyuan xue, Yang Fu
Most studies focus on the first and second signals of T cell activation. However, the roles of cytokines in immunotherapy are not fully understood, and cytokines have not been widely used in patient care. Clinical application of cytokines is limited due to their short half-life in vivo, severe toxicity at therapeutic doses, and overall lack of efficacy. Several modifications have been engineered to extend their half-life and increase tumor targeting, including polyethylene glycol conjugation, fusion to tumor-targeting antibodies, and alteration of cytokine/cell receptor-binding affinity. These modifications demonstrate an improvement in either increased antitumor efficacy or reduced toxicity. However, these cytokine engineering strategies may still be improved further, as each strategy poses advantages and disadvantages in the delicate balance of targeting tumor cells, tumor-infiltrating lymphocytes, and peripheral immune cells. This review focuses on selected cytokines, including i...
Cancer Immunology, Immunotherapy
Armed antibodies for cancer treatment: a promising tool in a changing era
2014 •
Mario Santinami
Cancer Research
Antitumor Immunity: Easy as 1, 2, 3 with Monoclonal Bispecific Trifunctional Antibodies?
2013 •
John Maher
Clinical Cancer Research
Therapeutic Antitumor Efficacy of Anti-CD137 Agonistic Monoclonal Antibody in Mouse Models of Myeloma
2008 •
Carlos Alfaro
