{"id":4852,"date":"2019-11-19T19:39:31","date_gmt":"2019-11-19T10:39:31","guid":{"rendered":"http:\/\/163.180.4.222\/lab\/?p=4852"},"modified":"2023-07-09T10:58:15","modified_gmt":"2023-07-09T01:58:15","slug":"trispecific-antibodies-offer-a-third-way-forward-for-anticancer-immunotherapy","status":"publish","type":"post","link":"https:\/\/biochemistry.khu.ac.kr\/lab\/?p=4852","title":{"rendered":"Trispecific antibodies offer a third way forward for anticancer immunotherapy & \uc57d \ud558\ub098\ub85c \ub450 \uac00\uc9c0 \uce58\ub8cc\ud6a8\uacfc\u2026\uc81c\uc57d\u793e ‘\uc774\uc911\ud56d\uccb4’\uc5d0 \uaf42\ud614\ub2e4"},"content":{"rendered":"

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Immunotherapy approaches seek to boost immune responses against cancer. A single antibody engineered to recognize three targets shows promise, when tested in animals, in improving the ability of T cells to target cancer.<\/h5>\n

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Antibodies with specificity for one target \u2014 called monoclonal antibodies \u2014 were the first cancer immunotherapy to achieve widespread clinical use. The therapeutic potency of antibodies can be amplified by engineering them to recognize two distinct molecular targets (termed antigens). These bispecific antibodies can simultaneously bind to cancer cells and immune cells called T cells, and this dual binding directs the T cell to unleash its cell-killing power towards the cancer cell.\u00a0Writing in\u00a0Nature Cancer<\/i><\/a>, Wu\u00a0et al.<\/i>1<\/a><\/sup>\u00a0now report the development of a trispecific antibody, one that has three targets: a cancer cell, a receptor that activates T cells, and a T-cell protein that promotes long-lasting T-cell activity against the cancer cell (Fig. 1).<\/p>\n

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Figure 1 | An antibody that helps immune cells to target cancer cells.<\/b>\u00a0Wu\u00a0et al<\/i>.1<\/a><\/sup>\u00a0report the development of a human antibody that is engineered to bring an immune cell called a T cell into close proximity with a type of cancer cell called a myeloma cell and to boost the T cell\u2019s anticancer response. This trispecific antibody binds three targets: the protein CD38 on a myeloma cell, and the protein CD28 and the protein complex CD3 on a T cell (the antibody\u2019s target-binding domains are shown in red, blue and yellow, respectively). CD3 is part of the T-cell receptor (TCR), which recognizes abnormal cells by binding molecules called antigens. The binding of CD3 by the antibody drives T-cell activation (without requiring antigen recognition by the TCR), which leads to the killing of the myeloma cell and the production and release of toxic cytokine molecules. Binding of CD28 by the antibody drives expression of the protein Bcl-xL. Bcl-xL blocks T-cell death, which might otherwise occur if there was prolonged TCR activation in the absence of CD28 stimulation by the antibody.<\/span><\/p>\n<\/figcaption><\/figure>\n

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The mammalian immune system generates an immense diversity of antibodies, and antibodies can also be engineered to recognize therapeutic targets. Antibodies usually recognize a single antigen, which might be part of a disease-causing agent or an abnormal version of a protein or sugar. Such monospecific antibodies against targets on cancer cells can recruit immune cells, including neutrophils, natural killer cells and macrophages, to kill or ingest the cancer cells.<\/p>\n

Antibodies can also be engineered to block or stimulate the function of the proteins to which they bind. For example, there are regulatory receptors that inhibit T-cell function, and antibodies that have been engineered to block these receptors provide a clinical strategy known as checkpoint blockade, which boosts T-cell function. These inhibitory receptors govern T-cell exhaustion, a non-functional T-cell state that protects against autoimmunity and that can occur in the tumour microenvironment as cancers evade antitumour responses mediated by T cells. Checkpoint-blockade treatment can awaken exhausted antitumour T cells to great clinical benefit, but it also risks causing autoimmune toxicity. The antibody developed by Wu and colleagues takes a similar approach to promote T-cell activity against cancer cells. However, their method stimulates the function of receptors that positively boost T-cell function, rather than blocking the function of inhibitory receptors.<\/p>\n

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