CD2 Immunobiology

Binder, Christian; Cvetkovski, Filip; Sellberg, Felix; Berg, Stefan; Visbal, Horacio Paternina; Sachs, David H.; Berglund, Erik; Berglund, David

doi:10.3389/fimmu.2020.01090

Cited by 84 publications

(88 citation statements)

References 158 publications

(219 reference statements)

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“…However, 10 hub genes were identified in the current study ( Figure 10B ). Among them, CD2 is a transmembrane glycoprotein typically known for its participation in the costimulatory pathway of T cell activation ( 58 ). TBX21 is essential for naive T lymphocyte development and interferon-gamma production ( 59 ).…”

Section: Discussionmentioning

confidence: 99%

Integrated Analysis of the ETS Family in Melanoma Reveals a Regulatory Role of ETV7 in the Immune Microenvironment

et al. 2020

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The ETS family modulates immune response and drug efficiency to targeted therapies, but their role in melanoma is largely unclear. In this study, the ETS family was systematically analyzed in multiple public data sets. Bioinformatics tools were used to characterize the function of ETV7 in melanoma. A prognostic model was constructed using the LASSO Cox regression method. We found that ETV7 was the only differentially expressed gene with significant prognostic relevance in melanoma. Enrichment analysis of seven independent data sets indicated ETV7 participation in various immune-related pathways. ETV7 particularly showed a strong positive correlation with CD8+ T cell infiltration. The prognostic model based on ETV7 and its hub genes showed a relatively good predictive value in training and testing data sets. Thus, ETV7 can potentially regulate the immune microenvironment in melanoma.

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Section: Discussionmentioning

confidence: 99%

Integrated Analysis of the ETS Family in Melanoma Reveals a Regulatory Role of ETV7 in the Immune Microenvironment

et al. 2020

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“…CD2 is a surface adhesion molecule expressed by a variety of cell populations including T cells, NK cells and DC ( 158 – 160 ). Notably, CD2 levels are increased on Tmem ( 158 , 159 ).…”

Section: The Application Of Depleting Mab For T1dmentioning

confidence: 99%

“…CD2 is a surface adhesion molecule expressed by a variety of cell populations including T cells, NK cells and DC ( 158 – 160 ). Notably, CD2 levels are increased on Tmem ( 158 , 159 ). Alefacept, a fusion protein consisting of the CD2-binding domain of LFA3 fused to the Fc region of human IgG1 (IgG1 Fc ), has been utilized to treat psoriasis ( 88 , 161 ).…”

Section: The Application Of Depleting Mab For T1dmentioning

confidence: 99%

Evolving Antibody Therapies for the Treatment of Type 1 Diabetes

et al. 2021

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Type 1 diabetes (T1D) is widely considered to be a T cell driven autoimmune disease resulting in reduced insulin production due to dysfunction/destruction of pancreatic β cells. Currently, there continues to be a need for immunotherapies that selectively reestablish persistent β cell-specific self-tolerance for the prevention and remission of T1D in the clinic. The utilization of monoclonal antibodies (mAb) is one strategy to target specific immune cell populations inducing autoimmune-driven pathology. Several mAb have proven to be clinically safe and exhibit varying degrees of efficacy in modulating autoimmunity, including T1D. Traditionally, mAb therapies have been used to deplete a targeted cell population regardless of antigenic specificity. However, this treatment strategy can prove detrimental resulting in the loss of acquired protective immunity. Nondepleting mAb have also been applied to modulate the function of immune effector cells. Recent studies have begun to define novel mechanisms associated with mAb-based immunotherapy that alter the function of targeted effector cell pools. These results suggest short course mAb therapies may have persistent effects for regaining and maintaining self-tolerance. Furthermore, the flexibility to manipulate mAb properties permits the development of novel strategies to target multiple antigens and/or deliver therapeutic drugs by a single mAb molecule. Here, we discuss current and potential future therapeutic mAb treatment strategies for T1D, and T cell-mediated autoimmunity.

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“…The glycoprotein CD2 (also known as LFA2) is expressed on T and NK cells where it serves as an adhesion and activation receptor ( 1 ). In humans, the main binding partner of CD2 is lymphocyte associated antigen 3 (LFA3; also known as CD58) which is broadly expressed, especially on antigen-presenting cells (APCs).…”

Section: Introductionmentioning

confidence: 99%

“…In humans, the main binding partner of CD2 is lymphocyte associated antigen 3 (LFA3; also known as CD58) which is broadly expressed, especially on antigen-presenting cells (APCs). CD2-targeting immunotherapy is a promising treatment for organ transplant recipients and patients suffering from autoimmune diseases [Reviewed in ( 1 )]. Siplizumab is a monoclonal anti-CD2 IgG1 antibody (anti-CD2 IgG1 mAb) that is currently undergoing clinical trials in the field of transplantation (ClinicalTrials.gov Identifier: NCT04311632).…”

Section: Introductionmentioning

confidence: 99%

Siplizumab Induces NK Cell Fratricide Through Antibody-Dependent Cell-Mediated Cytotoxicity

et al. 2021

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The glycoprotein CD2 is expressed on T and NK cells and contributes to cell-cell conjugation, agonistic signaling and actin cytoskeleton rearrangement. CD2 has previously been shown to have an important function in natural NK cell cytotoxicity but to be expendable in antibody-mediated cytotoxicity. Siplizumab is a monoclonal anti-CD2 IgG1 antibody that is currently undergoing clinical trials in the field of transplantation. This study investigated the effect of CD2 binding and Fc γ receptor binding by siplizumab (Fc-active) and Fc-silent anti-CD2 monoclonal antibodies in allogeneic mixed lymphocyte reaction and autologous lymphocyte culture. Further, induction of NK cell fratricide and inhibition of natural cytotoxicity as well as antibody-dependent cytotoxicity by these agents were assessed. Blockade of CD2 via monoclonal antibodies in the absence of Fc γ receptor binding inhibited NK cell activation in allogeneic mixed lymphocyte reaction. In contrast, siplizumab increased NK cell activation in both mixed lymphocyte reaction and autologous lymphocyte culture due to FcγRIIIA binding. However, experiments using purified NK cells did not show an inhibitory effect of CD2 blockade on natural cytotoxicity or antibody-dependent cytotoxicity. Lastly, it was shown that siplizumab induces NK cell fratricide. Concluding, siplizumab is a promising biopharmaceutical drug candidate for depletion of T and NK cells with minimal off-target effects.

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CD2 Immunobiology

Cited by 84 publications

References 158 publications

Integrated Analysis of the ETS Family in Melanoma Reveals a Regulatory Role of ETV7 in the Immune Microenvironment

Integrated Analysis of the ETS Family in Melanoma Reveals a Regulatory Role of ETV7 in the Immune Microenvironment

Evolving Antibody Therapies for the Treatment of Type 1 Diabetes

Siplizumab Induces NK Cell Fratricide Through Antibody-Dependent Cell-Mediated Cytotoxicity

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