Bispecific antibody platforms for cancer immunotherapy

Lameris, Roeland; Bruin, Renée C.G. de; Schneiders, Famke L.; Henegouwen, Paul M.P. van Bergen en; Verheul, Henk M.W.; Gruijl, Tanja D. de; Vliet, Hans J. van der

doi:10.1016/j.critrevonc.2014.08.003

Cited by 77 publications

(51 citation statements)

References 113 publications

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“…Strategies to deliver drugs to specific cell types are needed. Some approaches, such as transporter-mediated drug uptake 43 , bi-specific antibodies 44 , and nanoparticle-mediated delivery 45 , require further clinical evaluation.…”

Section: Integrating Knowledge and Keeping Metabolism In Mind When Dementioning

confidence: 99%

Emerging concepts of T cell metabolism as a target of immunotherapy

2016

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Metabolism is the set of biochemical reactions that allows cells to acquire and utilize nutrients needed to sustain life. Accessing nutrients and meeting metabolic demands are necessary for cells to survive, proliferate, and to properly perform their intended functions. During an immune response leukocytes undergo major changes in growth and function that are tightly coupled to dynamic shifts in metabolic processes. Immunometabolism is an emerging field that investigates the interplay between immunological and metabolic processes. Interest in this field stems from the realization that incorrect metabolic remodeling underlies many aberrant immune responses, and that manipulating cellular metabolism can beneficially enhance or temper immunity.

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Section: Integrating Knowledge and Keeping Metabolism In Mind When Dementioning

confidence: 99%

Emerging concepts of T cell metabolism as a target of immunotherapy

2016

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“…Bi-specific antibodies are engineered proteins composed of two independently targeted Fab regions within an antibody, or two separate antibodies, targeted against distinct epitopes, connected by a linker protein [131, 132]. These proteins have been primarily explored as cancer therapies where the bi-specific antibody is used to simultaneously bind both a tumor cell and cytotoxic T cell [133, 134], or in the case of tri-functional antibodies, the protein can additionally bind a cell with a Fc receptor, such as a macrophage or dendritic cell [135]. The result of this association is to bring these cells into close proximity, so that the T cells can kill the tumor cells in a targeted fashion [131, 132].…”

Section: Targeting Metabolism Therapeuticallymentioning

confidence: 99%

Targeting T cell metabolism for therapy

O’Sullivan

Pearce

2015

Trends in Immunology

219

176

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In the past several years, a wealth of evidence has emerged illustrating how metabolism supports many aspects of T cell biology, as well as how metabolic changes drive T cell differentiation and fate. Here we outline developing principles in the regulation of T cell metabolism, and discuss how these processes are impacted in settings of inflammation and cancer. In this context we discuss how metabolic pathways might be manipulated for the treatment of human disease, including how metabolism may be targeted to prevent T cell dysfunction in inhospitable microenvironments, to generate more effective adoptive cellular immunotherapies in cancer, and to direct T cell differentiation and function towards non-pathogenic phenotypes in settings of autoimmunity.

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“…Several bi-specific antibody (BsAb) platforms have been developed to redirect T cell activity to TAAs. The fusion of two single chain variable fragments (ScFv) via a flexible linker peptide yields tandem ScFvs (TaFv), chimeras that provide the minimal protein sequence needed for antigenic recognition as well as the flexibility necessary to enable interaction with multiple targets (30). TaFv molecules can be designed to target any two antigens that may exist within close proximity to each other, and also may be utilized to target an antigenic peptide and simultaneously activate an immune response.…”

Section: Redirecting Resident T Cells To Tumor-associated Antigensmentioning

confidence: 99%

“…The latter approach has exhibited promising results: TaFv molecules have been engineered to include specificity to the TCR molecule CD3 as well as a TAA, termed bi-specific T cell engagers (BiTEs). BiTEs can redirect polyclonal T cells within the tumor to elicit a TAA-specific response, potentially activating multiple cycles of target cell killing (30). Most notably, a phase I clinical trial employing MT110, a CD3/EpCAM (epithelial cell adhesion molecule) BiTE for the treatment of solid tumors including lung, gastric, colorectal, breast, prostate, and ovarian cancers, was recently completed (NCT00635596).…”

Section: Redirecting Resident T Cells To Tumor-associated Antigensmentioning

confidence: 99%

The Evolution of T-cell Therapies for Solid Malignancies

Fousek

Ahmed

2015

Clinical Cancer Research

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Primary resistant, recurrent and relapsed solid tumors are often non-responsive to conventional anti-neoplastic therapies. Moreover, in responsive tumors, the therapeutic to toxic range of these interventions remains quite narrow, such that side effects of therapy are substantial. Targeted therapies, such as adoptive T cell transfer, not only spare normal tissues but also use alternative killing mechanisms to which the tumor cells are usually not immune. Adoptive T cell transfer for solid tumors faces unique challenges because of the inherent heterogeneity of tumor parenchyma, the complexity of the tumor microenvironment, and tumor occurrence in areas with limited therapeutic accessibility. In this review, we examine the recent evolution of various T cell-based immunotherapeutics, the mechanisms of action behind their antitumor activity, their increasing complexity, and the prospect of building on previous successes in the treatment of solid tumors.

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Bispecific antibody platforms for cancer immunotherapy

Cited by 77 publications

References 113 publications

Emerging concepts of T cell metabolism as a target of immunotherapy

Emerging concepts of T cell metabolism as a target of immunotherapy

Targeting T cell metabolism for therapy

The Evolution of T-cell Therapies for Solid Malignancies

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