A Single-Step Chemoenzymatic Reaction for the Construction of Antibody–Cell Conjugates

Li, Jie; Chen, Mingkuan; Liu, Zilei; Zhang, Linda; Felding, Brunie H.; Moremen, Kelley W.; Lauvau, Grégoire; Abadier, Michael; Ley, Klaus; Wu, Peng

doi:10.1021/acscentsci.8b00552

Cited by 65 publications

(75 citation statements)

References 37 publications

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“…By engineering the cell-surface landscape, cells can be endowed with the desired properties. In our previous studies 42 (Supplementary figure s15). It is apparent that there is sufficiently high level of endogenous un-sialylated LacNAc residues that can be readily modified by ST6Gal1…”

Section: Conclusion and Discussionmentioning

confidence: 83%

Glycoengineering of NK cells with glycan ligands of CD22 and selectins for B-cell lymphoma therapy

Hong

Wang

et al. 2020

Preprint

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CD22, a member of Siglec family of sialic acid binding proteins, has restricted expression on B cells. Antibody-based agents targeting CD22 or CD20 (Rituxan TM ) on B lymphoma and leukemia cells exhibit clinical efficacy for treating these malignancies, but also attack normal B cells leading to immune deficiency. Here, we report a chemoenzymatic glycocalyx editing strategy to introduce high-affinity and specific CD22 ligands onto NK-92MI and cytokine-induced killer (CIK) cells to achieve tumor-specific CD22 targeting. These CD22-ligand modified cells exhibited significantly enhanced tumor cell binding and killing in vitro without harming healthy B cells. For effective lymphoma cell killing in vivo we further functionalized CD22 ligand-modified NK-92MI cells with the E-selectin ligand sialyl Lewis X to promote trafficking to bone marrow. The cells containing the ligands of both CD22 and selectins resulted in the efficient suppression of B lymphoma in a xenograft model.Our results suggest that NK cells modified with glycan ligands to CD22 and selectins promote both targeted killing of B lymphoma cells and improved trafficking to sites where the cancer cells reside, respectively.

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Section: Conclusion and Discussionmentioning

confidence: 83%

Glycoengineering of NK cells with glycan ligands of CD22 and selectins for B-cell lymphoma therapy

Hong

Wang

et al. 2020

Preprint

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“…In this way, T cells obtain specific tumor targeting capacity and resistance to inhibitory signals produced by tumor cells. 116…”

Section: Chemoenzymatic Glycoengineeringmentioning

confidence: 99%

Human T cell glycosylation and implications on immune therapy for cancer

Bousser

Meuris

Callewaert

et al. 2020

Human Vaccines & Immunotherapeutics

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Glycosylation is an important post-translational modification, giving rise to a diverse and abundant repertoire of glycans on the cell surface, collectively known as the glycome. When focusing on immunity, glycans are indispensable in virtually all signaling and cell-cell interactions. More specifically, glycans have been shown to regulate key pathophysiological steps within T cell biology such as T cell development, thymocyte selection, T cell activity and signaling as well as T cell differentiation and proliferation. They are of major importance in determining the interaction of human T cells with tumor cells. In this review, we will describe the role of glycosylation of human T cells in more depth, elaborate on the importance of glycosylation in the interaction of human T cells with tumor cells and discuss the potential of cancer immunotherapies that are based on manipulating the glycome functions at the tumor immune interface.

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“…Previously, we developed a chemoenzymatic method that enables us to conjugate proteins onto the cell surface (Li et al, 2018). This method relies on a1-3-fucosyltransferase (FT), a glycosyltransferase possessing remarkable donor substrate tolerance.…”

Section: Install H Pylori α1-3-fucosyltransferase (Ft) Onto the Cellmentioning

confidence: 99%

Detecting Tumor Specific Antigen-Reactive T cells from Tumor Infiltrating Lymphocytes via Interaction Dependent Fucosyl-biotinylation

Liu

Chen

et al. 2020

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HighlightsInteraction dependent fucosylation enables the detection and isolation of bona fide intratumoral tumor specific antigen-reactive T cells Tumor specific antigen-reactive CD8 + T cells possess capabilities to be expanded and adoptively transferred for tumor control Tumor specific antigen-reactive CD8 + T cells feature oligoclonal expansion and upregulate genes for the steroid biosynthesis and metabolic process Intratumoral bystander CD8 + T cells can be separated into two groups based on PD-1 expression that feature distinct gene modules SummaryRe-activation and clonal expansion of tumor specific antigen (TSA)-reactive T cells are critical to the success of checkpoint blockade and adoptive transfer of tumor-infiltrating lymphocyte (TIL) based therapies. There are no reliable markers to specifically identify the repertoire of TSA-reactive T cells due to their heterogeneous composition. Here we introduce FucoID as a general platform to detect endogenous antigen-specific T cells and study their biology. Through this interaction dependent labeling approach, TSA-reactive T cells can be detected and separated from bystander T cells in primary tumor digests based on their cell-surface enzymatic fucosylbiotinylation. Compared to bystander TILs, TSA-reactive TILs possess a distinct TCR repertoire and unique gene features. Though exhibiting a dysfunctional phenotype, this subset of TILs possesses substantial capabilities of proliferation and tumor specific killing. FucoID features genetic manipulation-free procedures and a quick turnover cycle, and therefore should have the potential of accelerating the pace of personalized cancer treatment.

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A Single-Step Chemoenzymatic Reaction for the Construction of Antibody–Cell Conjugates

Cited by 65 publications

References 37 publications

Glycoengineering of NK cells with glycan ligands of CD22 and selectins for B-cell lymphoma therapy

Glycoengineering of NK cells with glycan ligands of CD22 and selectins for B-cell lymphoma therapy

Human T cell glycosylation and implications on immune therapy for cancer

Detecting Tumor Specific Antigen-Reactive T cells from Tumor Infiltrating Lymphocytes via Interaction Dependent Fucosyl-biotinylation

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