Melanoma cells can be eliminated by sialylated CD43 × CD3 bispecific T cell engager formats in vitro and in vivo

Jong, Greta de; Bartels, Lina; Kedde, Martijn; Verdegaal, Els M.E.; Gillissen, Marijn A.; Levie, Sophie E.; Cercel, Madalina G.; Veen, Susan E. van Hal-van; Fatmawati, Christien; Berg, Dorien van de; Yasuda, Etsuko; Claassen, Yvonne; Bakker, Arjen Q.; Burg, Sjoerd H. van der; Schotte, Remko; Villaudy, Julien; Spits, Hergen; Hazenberg, Mette D.; Helden, Pauline M. van; Wagner, Kay Uwe

doi:10.1007/s00262-020-02780-9

Cited by 9 publications

(6 citation statements)

References 49 publications

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“…These antibodies increased T-cell cytotoxicity against melanoma cells in vitro with a certain potency. In line with this, TCEs treatment in mice harboring a human immune system grafted with A375 melanoma cells induced a strong tumor growth inhibition and T-cell engagement, indicating that CD43s-binding receptors on T cells may orchestrate immune evasion during melanoma progression [53]. In brief, these findings provide novel T-cell engaging antibodies that might be combined with current immunotherapies in melanoma.…”

Section: Sialylationsupporting

confidence: 55%

“…Sialylated CD43 (CD43s) is expressed by hematologic malignancies, and it is recognized by the monoclonal antibody AT1413 [52]. De Jong and colleagues immunoprecipitated CD43s from melanoma cells, confirming that AT1413 could bind to CD43s in melanoma [53]. AT1413 was unable to affect growth of melanoma cells in vivo, but induced antibody-dependent cellular cytotoxicity against short-term patient-derived melanoma cells.…”

Section: Sialylationmentioning

confidence: 99%

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The Role of Glycosylation in Melanoma Progression

Vellis¹,

Pietrobono²,

Stecca³

2021

Cells

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Malignant melanoma is the most aggressive form of skin cancer, which originates from the malignant transformation of melanocytes, the melanin-producing cells of the skin. Melanoma progression is typically described as a stepwise process in which metastasis formation ensues late during disease. A large body of evidence has shown that the accumulation of genetic and epigenetic alterations drives melanoma progression through the different steps. Mortality in melanoma is associated with metastatic disease. Accordingly, early-stage melanoma can be cured in the majority of cases by surgical excision, while late-stage melanoma is a highly lethal disease. Glycosylation is a post-translational modification that involves the transfer of glycosyl moieties to specific amino acid residues of proteins to form glycosidic bonds through the activity of glycosyltransferases. Aberrant glycosylation is considered a hallmark of cancer as it occurs in the majority of tumor types, including melanoma. The most widely occurring glycosylation changes in melanoma are represented by sialylation, fucosylation, and N- and I-glycan branching. In this review, we discuss the role of glycosylation in melanoma and provide insights on the mechanisms by which aberrant glycosylation promotes melanoma progression through activation of invasion and metastasis, immune evasion and cell proliferation.

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Section: Sialylationsupporting

confidence: 55%

Section: Sialylationmentioning

confidence: 99%

The Role of Glycosylation in Melanoma Progression

Vellis¹,

Pietrobono²,

Stecca³

2021

Cells

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“…In conclusion, bispecific antibodies modified by different methods can achieve specific useful functions, including the regulation of immunogenicity, effector function and antibody half-life. Bispecific antibodies also kill tumor cells expressing specific targets, including internal tumor antigens and increase the number of effector T cells in tumor lesions ( Weisbart et al, 2012 ; Ma et al, 2019 ; de Jong et al, 2021 ).…”

Section: Basic Characteristics Of Bispecific Antibodiesmentioning

confidence: 99%

“…Two functional T-cell engager forms of AT1413 were synthesized, and the dual bivalent b T-cell engager format is approximately 50 times more effective than the unit price KiH format. These T-cell engagers effectively activate T cells to kill melanoma cells ( de Jong et al, 2021 ) ( Figure 3 ).…”

Section: Basic Characteristics Of Bispecific Antibodiesmentioning

confidence: 99%

Bispecific Antibodies Progression in Malignant Melanoma

Tang

Gong

2022

Front. Pharmacol.

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The discovery of oncogenes and immune checkpoints has revolutionized the treatment of melanoma in the past 10 years. However, the current PD-L1 checkpoints lack specificity for tumors and target normal cells expressing PD-L1, thus reducing the efficacy on malignant melanoma and increasing the side effects. In addition, the treatment options for primary or secondary drug-resistant melanoma are limited. Bispecific antibodies bind tumor cells and immune cells by simultaneously targeting two antigens, enhancing the anti-tumor targeting effect and cytotoxicity and reducing drug-resistance in malignant melanoma, thus representing an emerging strategy to improve the clinical efficacy. This review focused on the treatment of malignant melanoma by bispecific antibodies and summarized the effective results of the experiments that have been conducted, also discussing the different aspects of these therapies. The role of the melanoma epitopes, immune cell activation, cell death and cytotoxicity induced by bispecific antibodies were evaluated in the clinical or preclinical stage, as these therapies appear to be the most suitable in the treatment of malignant melanoma.

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“…T-BsAbs that target B7-H3, B7-H4, or B7-H6 have shown promising antitumor effects in mouse models against melanoma, breast cancer, and ovarian cancer, respectively [124][125][126]. Other distinctive target antigens include a lyase, a Wnt signaling regulator, an orphan receptor, and a sialylated cluster of differentiation (CD) antigen [57,[127][128][129]. Several T-BsAbs mentioned here are now in clinical trials for evaluation of their efficacy and safety.…”

Section: Preclinical Researchmentioning

confidence: 99%

T Cell Bispecific Antibodies: An Antibody-Based Delivery System for Inducing Antitumor Immunity

2021

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As a breakthrough immunotherapy, T cell bispecific antibodies (T-BsAbs) are a promising antibody therapy for various kinds of cancer. In general, T-BsAbs have dual-binding specificity to a tumor-associated antigen and a CD3 subunit forming a complex with the TCR. This enables T-BsAbs to crosslink tumor cells and T cells, inducing T cell activation and subsequent tumor cell death. Unlike immune checkpoint inhibitors, which release the brake of the immune system, T-BsAbs serve as an accelerator of T cells by stimulating their immune response via CD3 engagement. Therefore, they can actively redirect host immunity toward tumors, including T cell recruitment from the periphery to the tumor site and immunological synapse formation between tumor cells and T cells. Although the low immunogenicity of solid tumors increases the challenge of cancer immunotherapy, T-BsAbs capable of immune redirection can greatly benefit patients with such tumors. To investigate the detailed relationship between T-BsAbs delivery and their T cell redirection activity, it is necessary to determine how T-BsAbs deliver antitumor immunity to the tumor site and bring about tumor cell death. This review article discusses T-BsAb properties, specifically their pharmacokinetics, redirection of anticancer immunity, and local mechanism of action within tumor tissues, and discuss further challenges to expediting T-BsAb development.

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Melanoma cells can be eliminated by sialylated CD43 × CD3 bispecific T cell engager formats in vitro and in vivo

Cited by 9 publications

References 49 publications

The Role of Glycosylation in Melanoma Progression

The Role of Glycosylation in Melanoma Progression

Bispecific Antibodies Progression in Malignant Melanoma

T Cell Bispecific Antibodies: An Antibody-Based Delivery System for Inducing Antitumor Immunity

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