We are analyzing https://link.springer.com/article/10.1007/s00262-010-0844-y.

Title:
Epitope distance to the target cell membrane and antigen size determine the potency of T cell-mediated lysis by BiTE antibodies specific for a large melanoma surface antigen | Cancer Immunology, Immunotherapy
Description:
Melanoma chondroitin sulfate proteoglycan (MCSP; also called CSPG4, NG2, HMW-MAA, MSK16, MCSPG, MEL-CSPG, or gp240) is a surface antigen frequently expressed on human melanoma cells, which is involved in cell adhesion, invasion and spreading, angiogenesis, complement inhibition, and signaling. MCSP has therefore been frequently selected as target antigen for development of antibody- and vaccine-based therapeutic approaches. We have here used a large panel of monoclonal antibodies against human MCSP for generation of single-chain MCSP/CD3-bispecific antibodies of the BiTE (for bispecific T cell engager) class. Despite similar binding affinity to MCSP, respective BiTE antibodies greatly differed in their potency of redirected lysis of CHO cells stably transfected with full-length human MCSP, or with various MCSP deletion mutants and fusion proteins. BiTE antibodies binding to the membrane proximal domain D3 of MCSP were more potent than those binding to more distal domains. This epitope distance effect was corroborated with EpCAM/CD3-bispecific BiTE antibody MT110 by testing various fusion proteins between MCSP and EpCAM as surface antigens. CHO cells expressing small surface target antigens were generally better lysed than those expressing larger target antigens, indicating that antigen size was also an important determinant for the potency of BiTE antibody. The present study for the first time relates the positioning of binding domains and size of surface antigens to the potency of target cell lysis by BiTE-redirected cytotoxic T cells. In case of the MCSP antigen, this provides the basis for selection of a maximally potent BiTE antibody candidate for development of a novel melanoma therapy.
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Keywords {🔍}

article, google, scholar, pubmed, cas, cancer, antibody, cell, cells, antigen, melanoma, human, baeuerle, bite, antibodies, kufer, mcsp, tumor, target, proteoglycan, singlechain, antigens, therapy, access, lutterbuese, content, immunotherapy, surface, stallcup, monoclonal, res, usa, immunother, biol, privacy, cookies, research, potency, lysis, bispecific, science, patients, immunol, schlereth, publish, search, epitope, membrane, size, large,

Topics {✒️}

single-chain mcsp/cd3-bispecific antibodies antigen-loaded antigen-presenting cells anti-cancer pro-inflammatory effects chondroitin sulfate proteoglycan month download article/chapter monoclonal antimelanoma antibody-ricin humoral anti-hmw-maa immunity anti-epcam × anti-cd3 bispecific-antibody-mediated killing vaccine-based therapeutic approaches 2025 autoantigen-specific immunosuppression human t-cell receptor cd8 + t-cell content full-length human mcsp cell-engaging antibody adoptive cell transfer specific monoclonal antibody article cancer immunology membrane-spanning proteoglycan full article pdf peptide-mhc antigen bite antibodies specific human melanoma cells ige antibody targeting trifunctional antibody catumaxomab privacy choices/manage cookies ng2 proteoglycan enhances ng2 proteoglycan leads treat metastatic melanoma human glioblastoma cells target cell lysis conejo-garcia jr eradicating established tumors ectodomain fragment human malignant melanoma antigen size determine cancer research center target cell membrane bite antibodies binding epitope distance effect genetically retargeted human melanoma therapy cell receptor recognition stage iv melanoma cell-mediated lysis bite antibody mcsp deletion mutants article bluemel bite-redirected cytotoxic anti-tumor activity

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         headline:Epitope distance to the target cell membrane and antigen size determine the potency of T cell-mediated lysis by BiTE antibodies specific for a large melanoma surface antigen
         description:Melanoma chondroitin sulfate proteoglycan (MCSP; also called CSPG4, NG2, HMW-MAA, MSK16, MCSPG, MEL-CSPG, or gp240) is a surface antigen frequently expressed on human melanoma cells, which is involved in cell adhesion, invasion and spreading, angiogenesis, complement inhibition, and signaling. MCSP has therefore been frequently selected as target antigen for development of antibody- and vaccine-based therapeutic approaches. We have here used a large panel of monoclonal antibodies against human MCSP for generation of single-chain MCSP/CD3-bispecific antibodies of the BiTE (for bispecific T cell engager) class. Despite similar binding affinity to MCSP, respective BiTE antibodies greatly differed in their potency of redirected lysis of CHO cells stably transfected with full-length human MCSP, or with various MCSP deletion mutants and fusion proteins. BiTE antibodies binding to the membrane proximal domain D3 of MCSP were more potent than those binding to more distal domains. This epitope distance effect was corroborated with EpCAM/CD3-bispecific BiTE antibody MT110 by testing various fusion proteins between MCSP and EpCAM as surface antigens. CHO cells expressing small surface target antigens were generally better lysed than those expressing larger target antigens, indicating that antigen size was also an important determinant for the potency of BiTE antibody. The present study for the first time relates the positioning of binding domains and size of surface antigens to the potency of target cell lysis by BiTE-redirected cytotoxic T cells. In case of the MCSP antigen, this provides the basis for selection of a maximally potent BiTE antibody candidate for development of a novel melanoma therapy.
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            T cell
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      headline:Epitope distance to the target cell membrane and antigen size determine the potency of T cell-mediated lysis by BiTE antibodies specific for a large melanoma surface antigen
      description:Melanoma chondroitin sulfate proteoglycan (MCSP; also called CSPG4, NG2, HMW-MAA, MSK16, MCSPG, MEL-CSPG, or gp240) is a surface antigen frequently expressed on human melanoma cells, which is involved in cell adhesion, invasion and spreading, angiogenesis, complement inhibition, and signaling. MCSP has therefore been frequently selected as target antigen for development of antibody- and vaccine-based therapeutic approaches. We have here used a large panel of monoclonal antibodies against human MCSP for generation of single-chain MCSP/CD3-bispecific antibodies of the BiTE (for bispecific T cell engager) class. Despite similar binding affinity to MCSP, respective BiTE antibodies greatly differed in their potency of redirected lysis of CHO cells stably transfected with full-length human MCSP, or with various MCSP deletion mutants and fusion proteins. BiTE antibodies binding to the membrane proximal domain D3 of MCSP were more potent than those binding to more distal domains. This epitope distance effect was corroborated with EpCAM/CD3-bispecific BiTE antibody MT110 by testing various fusion proteins between MCSP and EpCAM as surface antigens. CHO cells expressing small surface target antigens were generally better lysed than those expressing larger target antigens, indicating that antigen size was also an important determinant for the potency of BiTE antibody. The present study for the first time relates the positioning of binding domains and size of surface antigens to the potency of target cell lysis by BiTE-redirected cytotoxic T cells. In case of the MCSP antigen, this provides the basis for selection of a maximally potent BiTE antibody candidate for development of a novel melanoma therapy.
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         MCSP
         Melanoma
         T cell
         Redirected lysis
         Epitope
         Cytolytic synapse
         Oncology
         Immunology
         Cancer Research
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