From relapses and metastases
Surgical removal is the main method of treating solid tumors, but there is a risk that a small number of cancer cells remaining in the body after surgery can cause the tumor to grow and spread again. Cancer immunotherapy is one of the most powerful strategies to combat relapses, either in the form of monotherapy or in combination with other treatments. However, complex physiological changes in the microenvironment after surgery, especially the inflammatory condition caused by wound healing, and immunosuppression in response to this inflammation, reduce the effectiveness of immunotherapy.
Researchers from the University of Wisconsin-Madison have developed a gel that slowly releases two key components into the surgical area that restrain relapse and metastasis in the postoperative period. One of the components of the gel is the drug pexidartinib, which is approved by the FDA for the treatment of tenosynovial giant cell tumor, it inhibits tumor-associated macrophages and slows down the growth of neoplasms. The second component is platelets conjugated with antibodies to the programmed cell death protein (PD-1). They help T-lymphocytes recognize and attack cancer cells. Thus, the gel simultaneously depletes macrophages blocking the immune response and activates T-lymphocytes against cancer cells.
A new hydrogel (blue) containing anti-PD-1 conjugated platelets (red) and nanoparticles releasing pexidartinib (green).
The group tested the gel on mouse models of several types of cancer and found that it effectively restrained both tumors that respond well to immunotherapy (colon cancer CT26) and those less sensitive to immune therapy and more prone to metastasis (melanoma B16F10, sarcoma S180 and triple negative breast cancer 4T1).
Researchers have shown that the local release of anti-PD-1-conjugated platelets and pexidartinib near the tumor enhances the effects of both components and minimizes the side effects that occur with intravenous administration of these drugs. The gel decomposes safely over time and is excreted from the body.
The results obtained will be tested in studies on other animal models.
Article Z.Li et al. Depletion of tumor associated macrophages enhances local and systemic platelet-mediated anti-PD-1 delivery for post-surgery tumor recurrence treatment is published in the journal Nature Communications.
Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru based on the materials of the University of Wisconsin–Madison: Biodegradable gel boosts immune system's attack on several cancers in mice.