CTLA4<\/b><\/u><\/strong><\/a>: <\/b><\/strong>A new principle for immune therapy<\/b><\/strong><\/p>\n Cytotoxic T lymphocyte antigen 4 (CTLA4), structurally related to CD28<\/u><\/a>, delivers an inhibitory signal after ligation to CD80\/86, resulting in the termination of T cell immune responses. Increased CTLA-4:\u00a0B7 binding can result in a net negative signal, which limits IL-2 production and proliferation, and limits survival of the T cell. There are many\u00a0research teams exploited the mechanism as a target in the treatment of autoimmune disease.\u00a0Allison, however, had an entirely different idea. He had already developed an antibody that could bind to CTLA-4 and block its function. During the 1990s, in his laboratory at the University of California, Berkeley, James P. Allison studied the T-cell protein CTLA-4.\u00a0In 1994, they found\u00a0that blockade of the inhibitory effects of CTLA-4 can allow for, and potentiate, effective immune responses against tumor cells. In 2010, they performed an important clinical study, and in their excitement it showed striking effects in patients with advanced melanoma, a type of skin cancer. In several patients signs of remaining cancer disappeared. These results suggest that blockade of the inhibitory effects of CTLA-4 can allow for, and potentiate, effective immune responses against tumor cells.<\/p>\n PD-1<\/b><\/u><\/strong><\/a>: Important<\/b><\/strong>\u00a0for cancer therapy<\/b><\/strong><\/p>\n PD-1 is a member of the B7\/CD28 family of costimulatory receptors. It regulates T-cell activation through binding to its ligands, programmed death ligand 1 (PD-L1) and programmed death ligand 2 (PD-L2)\uff0csimilar to CTLA-4, functions as a T-cell brake, but operates by a different mechanism.\u00a0PD-1 inhibits effector T-cell activity at later-stage immune responses in peripheral tissues and in the tumor microenvironment.\u00a0Tasuku Honjo\u00a0and other group found that PD-1 demonstrate clear efficacy in the treatment of patients with different types of cancer. Results were dramatic, leading to long-term remission and possible cure in several patients with metastatic cancer, a condition that had previously been considered essentially untreatable.<\/p>\n Fig1. Combination therapy of CTLA-4 antibody and PD-1 antibody<\/p>\n Immune checkpoint therapy for cancer today and in the future<\/b><\/strong><\/p>\n Basic and translational studies in the 20 years since CTLA-4\u00a0and PD-1\u2019s discovery have demonstrated the concept of immune surveillance in mice and humans. The recovery of T-cell anergy by blocking CTLA-4 and PD-1 signals on T cells yielded incredible clinical benefits for several types of malignancies.\u00a0At present, a number of clinical trials have been conducted on the combination therapy of CTLA-4 antibody and PD-1 antibody.\u00a0Recently, BMS has published a large number of clinical data: PD-1 antibody Opdivo combined with CTLA-4 antibody Yervoy first-line clinical data for advanced renal cancer, the effective rate is as high as 41.6% (this clinical trial code CheckMate-214, is a global The center\u2019s large phase III clinical trial).In June.2017,\u00a0an article in the Science publication Science Translational Medicine used PD-1 and CTLA-4 antibodies to disrupt the \u201cbrake mechanism\u201d\u00a0of immune cells and in combination with chemotherapy, can effectively inhibit the growth of tumors carrying BRCA1 <\/u><\/a>mutations, improve the survival rate of animal models\u00a0significantly, revealing a combination strategy against malignant breast cancer\u00a0for the first time.<\/p>\n Conclusion<\/b><\/strong><\/p>\n Therefore, Allison and Honjo encourage people to work together to combine different strategies to release the immune system\u2019s brakes in order to more effectively eliminate tumor cells. A large number of checkpoint treatment trials are currently underway for most types of cancer, and new checkpoint proteins are being tested as targets.<\/p>\n <\/p>\n Announcement of the 2018 Nobel Prize in Physiology or Medicine by Professor Thomas Perlmann, Secretary of the Nobel Committee for Physiology or Medicine, on 1 October 2018.\u00a0It was awarded jointly […]<\/p>\n","protected":false},"author":1,"featured_media":874,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":[],"categories":[70],"tags":[76,531,530,56,276],"_links":{"self":[{"href":"https:\/\/www.bocsci.com\/blog\/wp-json\/wp\/v2\/posts\/873"}],"collection":[{"href":"https:\/\/www.bocsci.com\/blog\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.bocsci.com\/blog\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.bocsci.com\/blog\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/www.bocsci.com\/blog\/wp-json\/wp\/v2\/comments?post=873"}],"version-history":[{"count":1,"href":"https:\/\/www.bocsci.com\/blog\/wp-json\/wp\/v2\/posts\/873\/revisions"}],"predecessor-version":[{"id":876,"href":"https:\/\/www.bocsci.com\/blog\/wp-json\/wp\/v2\/posts\/873\/revisions\/876"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.bocsci.com\/blog\/wp-json\/wp\/v2\/media\/874"}],"wp:attachment":[{"href":"https:\/\/www.bocsci.com\/blog\/wp-json\/wp\/v2\/media?parent=873"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.bocsci.com\/blog\/wp-json\/wp\/v2\/categories?post=873"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.bocsci.com\/blog\/wp-json\/wp\/v2\/tags?post=873"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}![\"\"](\"http:\/\/www.bocsci.com\/blog\/wp-content\/uploads\/2018\/10\/Combination-therapy-of-CTLA-4-antibody-and-PD-1-antibody-300x300.png\")
<\/a><\/p>\nReferences<\/h4>\n
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