Trispecific killer engager 161519 enhances natural killer cell function and provides anti-tumor activity against CD19-positive cancers

Cheng, Ying; Zheng, Xiaodong; Wang, Xuefu; Chen, Yongyan; Wei, Haiming; Sun, Rui; Tian, Zhigang; Sun, Haoyu

doi:10.20892/j.issn.2095-3941.2020.0399

Cited by 30 publications

(16 citation statements)

References 38 publications

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“…“Armed” NK cells show stronger cytolytic activity than unarmed NK cells. In a preclinical B-cell lymphoma model of human peripheral blood mononuclear cell-reconstituted xenograft mice, 161519 TriKE treatment increased tumor growth inhibition and overall survival compared to CD16×CD19 BiKE treatment ( 38 ). Moreover, 1615133 (CD16×IL-15×CD133) TriKE provides IL-15 signaling, which supports the proliferation and survival of NK cells, inducing selective elimination of CSC of 16133 BiKE ( 39 ).…”

Section: Functional Mechanisms Of Bsabmentioning

confidence: 99%

Development of Bispecific Antibody for Cancer Immunotherapy: Focus on T Cell Engaging Antibody

et al. 2022

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In the era of immunotherapeutic control of cancers, many advances in biotechnology, especially in Ab engineering, have provided multiple new candidates as therapeutic immuno-oncology modalities. Bispecific Abs (BsAbs) that recognize 2 different antigens in one molecule are promising drug candidates and have inspired an upsurge in research in both academia and the pharmaceutical industry. Among several BsAbs, T cell engaging BsAb (TCEB), a new class of therapeutic agents designed to simultaneously bind to T cells and tumor cells via tumor cell specific antigens in immunotherapy, is the most promising BsAb. Herein, we are providing an overview of the current status of the development of TCEBs. The diverse formats and characteristics of TCEBs, in addition to the functional mechanisms of BsAbs are discussed. Several aspects of a new TCEB-Blinatumomab-are reviewed, including the current clinical data, challenges of patient treatment, drawbacks regarding toxicities, and resistance of TCEB therapy. Development of the next generation of TCEBs is also discussed in addition to the comparison of TCEB with current chimeric antigen receptor-T therapy.

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Section: Functional Mechanisms Of Bsabmentioning

confidence: 99%

Development of Bispecific Antibody for Cancer Immunotherapy: Focus on T Cell Engaging Antibody

et al. 2022

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“…To stimulate autologous NK cells and increase their survival, the NK-activating cytokine IL-15 is now frequently integrated into the molecules. For example, the 161519 TriKE is directed against the AR CD16 on NK cells, towards the B cell marker CD19, highly expressed on B cell malignancies, and contains IL-15 for additional NK cell activation [ 100 , 101 ]. A second generation TriKE (“161533”) directed at the myeloid leukemia cell marker CD33 shows improved characteristics in vitro [ 102 ].…”

Section: Harnessing Of Autologous Nk Cellsmentioning

confidence: 99%

A Hot Topic: Cancer Immunotherapy and Natural Killer Cells

Michel

Ollert

Zimmer

2022

IJMS

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Despite significant progress in recent years, the therapeutic approach of the multiple different forms of human cancer often remains a challenge. Besides the well-established cancer surgery, radiotherapy and chemotherapy, immunotherapeutic strategies gain more and more attention, and some of them have already been successfully introduced into the clinic. Among these, immunotherapy based on natural killer (NK) cells is considered as one of the most promising options. In the present review, we will expose the different possibilities NK cells offer in this context, compare data about the theoretical background and mechanism(s) of action, report some results of clinical trials and identify several very recent trends. The pharmaceutical industry is quite interested in NK cell immunotherapy, which will benefit the speed of progress in the field.

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“…A similar technology, DF1001, developed by Dragonfly and known as a TriNKET (Tri-specific NK Engager Therapy), is currently enrolling patients with HER2+ malignancies ( NCT04143711 ) although this structure has not been published( 59 ). Cheng et al have also published pre-clinical data utilizing a TriKE targeting CD19( 60 ). Taken together, these studies demonstrate the viability of NK cell engagers for clinical testing.…”

Section: Bi- and Tri- And Tetra-specific Killer Engagers (Bike/trike/tetrake)mentioning

confidence: 99%

Novel immune engagers and cellular therapies for metastatic castration-resistant prostate cancer: do we take a BiTe or ride BiKEs, TriKEs, and CARs?

Zorko

Ryan

2021

Prostate Cancer Prostatic Dis

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Background: Checkpoint inhibitors and currently approved cellular products for metastatic castration-resistant prostate cancer have not resulted in the revolutionary changes in outcomes compared to other solid tumors. Much of this lack of progress is attributed to the unique tumor microenvironment of prostate cancer that is often immunologically cold and immunosuppressive. These unique conditions emphasize the need for novel therapeutic options. In this review, we will discuss progress made in design of T- and NK cell immune engagers in addition to chimeric antigen receptor products specifically designed for prostate cancer that are currently under investigation in clinical trials. Methods: We searched peer-reviewed literature on the PubMed and the ClinicalTrials.gov databases for active clinical trials using the terms “bispecific T-cell engager,” “bispecific killer engager,” “trispecific killer engager,” “chimeric antigen receptor,” “metastatic castration-resistant prostate cancer,” and “neuroendocrine prostate cancer.” Results: Ten bispecific T-cell engager studies and nine chimeric antigen receptor-based products were found. Published data was compiled and presented based on therapeutic class. Conclusions: Multiple immune engagers and cell therapies are in the development pipeline and demonstrate promise to address barriers to better outcomes for metastatic castration-resistant prostate cancer patients.

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Trispecific killer engager 161519 enhances natural killer cell function and provides anti-tumor activity against CD19-positive cancers

Cited by 30 publications

References 38 publications

Development of Bispecific Antibody for Cancer Immunotherapy: Focus on T Cell Engaging Antibody

Development of Bispecific Antibody for Cancer Immunotherapy: Focus on T Cell Engaging Antibody

A Hot Topic: Cancer Immunotherapy and Natural Killer Cells

Novel immune engagers and cellular therapies for metastatic castration-resistant prostate cancer: do we take a BiTe or ride BiKEs, TriKEs, and CARs?

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