{"id":71,"date":"2018-05-24T05:54:15","date_gmt":"2018-05-24T05:54:15","guid":{"rendered":"https:\/\/www.creativebiolabs.net\/blog\/?p=71"},"modified":"2024-02-05T08:50:19","modified_gmt":"2024-02-05T08:50:19","slug":"antibody-expands-response-checkpoint","status":"publish","type":"post","link":"https:\/\/www.creativebiolabs.net\/blog\/antibody-expands-response-checkpoint\/","title":{"rendered":"Antibody Combo Expands Response to Checkpoint Inhibitor in Mice"},"content":{"rendered":"

Checkpoint inhibitor drugs, those that pull the brakes off the immune system, can cause dramatic improvements in cancer patients, but the benefits are far from universal. In the case of atezolizumab (Tecentriq), for instance, just about\u00a0a quarter of patients respond\u00a0to the medication.<\/span><\/p>\n

To find ways to boost the proportion of patients who respond to checkpoint inhibitors, researchers have turned to combination therapies. At the American Association for Cancer Research meeting in Chicago today (April 16), researchers from Genentech\u00a0presented data\u00a0showing atezolizumab<\/a><\/span><\/strong> combined with an antibody that interferes with transforming growth factor B (TGF-\u03b2) shrinks bladder cancer in mice that model recalcitrant tumors. The team had also published its results in February in\u00a0Nature<\/em>.<\/span><\/p>\n

Atezolizumab was given accelerated approval by the US Food and Drug Administration in 2016 to treat bladder cancer. The drug is a monoclonal antibody that works by binding to, and thereby inhibiting, programmed death-ligand 1 (PD-L1), a protein that ordinarily tamps down immune responses. To strategize ways of increasing the proportion of patients who benefit from the drug,\u00a0Sanjeev Mariathasan, a senior scientist at Genentech, and colleagues looked for differences in gene expression and genetic mutations of individuals who responded to atezolizumab compared with those who did not.<\/span><\/p>\n

The team found a number of differences between the patient groups, and several phenomena stood out: in particular, responders tended to have a higher load of tumor mutations, less TGF-\u03b2 signaling, and their tumors were infiltrated by T cells. Tumors of non-responders, on the other hand, had fewer mutations, more TGF-\u03b2 activity, and stromal tissue surrounding the tumor that impeded T cells from entering.<\/span><\/p>\n

\u201cThat would explain why anti-PD-L1 wouldn\u2019t work,\u201d coauthor\u00a0Ira Mellman, the vice president of cancer immunology at Genentech, tells\u00a0The Scientist<\/em>. \u201cT cells couldn\u2019t get in contact with the tumor cells they were supposed to kill.\u201d<\/span><\/p>\n

Mellman explains that TGF-\u03b2 plays a role in assembling the stroma, so the team suspected that inhibiting TGF-\u03b2 might help atezolizumab do its job. In mice bearing tumors that exclude T cells, the anti-TGF-\u03b2 antibody combined with the anti-PD-L1 antibody shrunk the tumors.<\/span><\/p>\n

The authors wouldn\u2019t reveal the precise target within the TGF-\u03b2 pathway that their antibody inhibits. Mellman says the antibody is not a drug currently approved for use in humans, and it remains to be seen whether it will be the best intervention to deal with resistant tumors. \u201cThis work provides a compelling reason to think there are one or more targets in this pathway that should be moved into clinic,\u201d he says.<\/span><\/p>\n

 <\/p>\n

Source: https:\/\/www.the-scientist.com\/?articles.view\/articleNo\/52297\/title\/Antibody-Combo-Expands-Response-to-Checkpoint-Inhibitor-in-Mice\/<\/p>\n","protected":false},"excerpt":{"rendered":"

Checkpoint inhibitor drugs, those that pull the brakes off the immune system, can cause dramatic improvements in cancer patients, but the benefits are far from universal. In the case of atezolizumab (Tecentriq),Read More…<\/a><\/p>\n","protected":false},"author":1,"featured_media":72,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[4,3,1],"tags":[7,10,11,5,6],"_links":{"self":[{"href":"https:\/\/www.creativebiolabs.net\/blog\/wp-json\/wp\/v2\/posts\/71"}],"collection":[{"href":"https:\/\/www.creativebiolabs.net\/blog\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.creativebiolabs.net\/blog\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.creativebiolabs.net\/blog\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/www.creativebiolabs.net\/blog\/wp-json\/wp\/v2\/comments?post=71"}],"version-history":[{"count":6,"href":"https:\/\/www.creativebiolabs.net\/blog\/wp-json\/wp\/v2\/posts\/71\/revisions"}],"predecessor-version":[{"id":437,"href":"https:\/\/www.creativebiolabs.net\/blog\/wp-json\/wp\/v2\/posts\/71\/revisions\/437"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.creativebiolabs.net\/blog\/wp-json\/wp\/v2\/media\/72"}],"wp:attachment":[{"href":"https:\/\/www.creativebiolabs.net\/blog\/wp-json\/wp\/v2\/media?parent=71"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.creativebiolabs.net\/blog\/wp-json\/wp\/v2\/categories?post=71"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.creativebiolabs.net\/blog\/wp-json\/wp\/v2\/tags?post=71"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}