{"id":23,"date":"2018-01-05T04:18:45","date_gmt":"2018-01-05T04:18:45","guid":{"rendered":"https:\/\/www.creativebiolabs.net\/blog\/?p=23"},"modified":"2024-02-05T08:44:00","modified_gmt":"2024-02-05T08:44:00","slug":"new-antibody-fight-bone-metasis","status":"publish","type":"post","link":"https:\/\/www.creativebiolabs.net\/blog\/new-antibody-fight-bone-metasis\/","title":{"rendered":"A new weapon against bone metastasis? Princeton lab develops antibody to fight cancer"},"content":{"rendered":"

“During the past<\/em> decade preclinical studies have defined many of the mechanisms used <\/em>by tumours to hijack the skeleton and promote bone metastasis. This has led to the development and widespread clinical use of bone-targeted drugs to prevent skeletal-related events. According to the mechanism, a new antibody is developed by <\/em>princeton lab to fight bone metastasis by undermining cancer’s defense strategy and allowing chemotherapy to work.”<\/em><\/p>\n

To explain his new weapon in the war against the metastatic spread of cancer to bone, Kang uses a movie metaphor: \u201cIndependence Day.\u201d<\/p>\n

In the 1996 blockbuster, the people of Earth fight back against alien attackers, deploying a computer virus to disable the shields guarding the attackers\u2019 spaceships. A new antibody, developed through a collaboration of Kang\u2019s lab with drug company Amgen, works similarly. Antibody 15D11 fights bone metastasis by undermining cancer\u2019s defense strategy and allowing chemotherapy to work.<\/p>\n

\u201cThe Kang Lab primarily studies breast cancer metastasis \u2014 how cancer cells spread from the breast to other organs \u2014 because what kills the vast majority of cancer patients is not the original tumor but rather metastasis,\u201d said Hanqiu Zheng, a former postdoctoral fellow with Kang and the lead author of the study\u00a0published Dec. 11\u00a0in the journal Cancer Cell, who is now an assistant professor at Tsinghua University in China.<\/p>\n

\u201cOur project specifically looked at bone metastasis and how cancer cells and bone cells \u2018talk\u2019 to each other through molecular signaling,\u201d said Rebecca Tang, Class of 2016, who worked with Kang for three years and is now a medical student at the University of Pennsylvania. \u201cPrevious work in the lab had shown that a molecule called Jagged1 is a critical part of this crosstalk and makes it easier for breast cancer cells to metastasize to bone. We therefore wanted to see if we could prevent or reduce metastasis by using an antibody called 15D11 to block Jagged1.\u201d<\/p>\n

Healthy bones are constantly being replenished in a two-part process:\u00a0Osteoclasts\u00a0(scrubbers) remove a layer of bone, and then osteoblasts (rebuilders) replenish the bone with new material.<\/p>\n

\u201cJust like if you have a bad driveway, and you use an excavator to remove the old surface and then you lay a new layer of it \u2014 that\u2019s how you maintain the integrity and strength of the bone tissue,\u201d Kang said.<\/p>\n

But in cancer patients, this system can be hijacked by the bone tumors, he said. The scrubbers can go into overdrive, removing bone tissue until almost nothing is left, or the rebuilders can be tricked into fostering the\u00a0growth of tumor cells\u00a0and protecting them during chemotherapy.<\/p>\n

\u201cTumors are essentially hiding in the cradles of the osteoblasts,\u201d Kang said.<\/p>\n

Initially, the researchers thought that 15D11 would only work against tumors that have a high expression of Jagged1, but then they found something surprising. When they paired their antibody with chemotherapy, it worked much better than either treatment alone, even in tumors without high level of Jagged1.<\/p>\n

\u201cThere\u2019s a synergy in combining the two agents,\u201d Zheng said. \u201cChemo alone is usually not very effective against bone metastasis.\u201d It can produce an initial reduction in the tumor burden, but only until it starts to induce Jagged1 expression in the rebuilder cells (osteoblasts), which the tumors can use as a shield.<\/p>\n

In most bone metastasis treatment, this is when tumors become resistant to chemotherapy and the treatment stops working. But because 15D11 specifically targets Jagged1, the antibody eliminates the protective effect of the rebuilders, allowing chemotherapy to continue keeping cancer at bay.<\/p>\n

To confirm that Jagged1 from osteoblasts protect cancer cells in bone, Kang collaborated with Dr. Brendan Lee at Baylor College of Medicine to create a genetically modified mouse strain that expresses Jagged1 in bone cells, making the mice much more susceptible to the growth of breast cancer cells in bone.<\/p>\n

In Kang\u2019s experiments, mice with the combined treatment of the antibody and chemotherapy stayed relatively healthy, compared with rapidly worsening conditions in mice treated with either 15D11 or chemotherapy alone. In one experiment, the tumor burden in bone decreased more than 100-fold with the combined treatment.<\/p>\n

\u201cThis is a remarkable response that we have never observed in any of our previous tests of therapeutic agents against bone metastasis in mice,\u201d Kang said. While the researchers haven\u2019t examined other cancers that also frequently metastasize to bone, such as prostate cancer, Kang said he suspects that the antibody would work on them as well.<\/p>\n

Kang hopes for a rapid path toward getting the antibody ready for human trials, he said. As the antibody is already fully human, having been created in a \u201chumanized mouse\u201d genetically engineered by Amgen, the next step is clinical trials in patients, if Amgen or another pharmaceutical partner chooses to move forward.<\/p>\n

\u201cThis work represents a major step forward,\u201d said Dr. Russell S. Taichman, associate dean for research at the University of Michigan School of Dentistry, who was not involved in this study. \u201cDeveloping a new therapeutic target\u00a0(the antibody), which may be useful in people, may change the clinical landscape [for] patients with early disease and those who develop outright metastasis. \u2026 Once again, the Kang group has hit it far out of the park!\u201d<\/p>\n

This research was supported by a Rutgers Cancer Institute of New Jersey (RCINJ) Research Development Award; the Brewster Foundation; and grants from METAvivor Research and Support (AWD1004691), the U.S. Department of Defense (BC123187), the National Institutes of Health (R01CA134519 and R01CA141062), and Amgen to Kang; and postdoctoral fellowships from Susan G. Komen to Zheng (KG111164) and Minhong Shen (PDF17332118); from the U.S. Department of Defense to Guangwen Ren (BC123284); and from the New Jersey Commission on Cancer Research to Shen (DFHS15PPCO21). This research was also supported by the Preclinical Imaging Facility and Pre-clinical Imaging and Flow Cytometry Shared Resources of the RCINJ (P30CA072720).<\/p>\n

Resource:\u00a0https:\/\/www.princeton.edu\/news\/2017\/12\/11\/new-weapon-against-bone-metastasis-princeton-lab-develops-antibody-fight-cancer<\/p>\n","protected":false},"excerpt":{"rendered":"

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