Recently, a study by the Dana-Farber Cancer Institute in the United States showed that during the surgical resection of a tumor, a gel containing an immunotherapeutic drug was implanted at the resection site to prevent tumors. Relapse and eradicate its metastatic growth. Related research is published online in Science Translational Medicine.
The researchers removed the tumor from a mouse model of breast cancer and placed a biodegradable gel containing an immunoagonist at the site of resection. Over time, the gel slowly released the drug, stimulating key immune cells. When the researchers examined the mice over the next few months, they found that this method cured more mice than other drug delivery techniques, and the tumor not only did not recur, but also at the drug release point. The metastatic tumor of the lungs has also been eliminated. Moreover, the experimental results were repeated in lung cancer and melanoma mice. This study provides an extremely important reference value for overcoming the two major obstacles in cancer treatment today (recurrence and spread of tumors).
"Surgical resection is the primary treatment for most solid tumor patients, but postoperative recurrence and spread are serious problems," said co-author Dr. Michael Darberg, assistant professor of Dana Farber and Harvard Medical School. "Even if the entire tumor is removed, there will still be a small number of tumor cells remaining." In fact, half of the cancer patients will undergo recurrence after surgery, and 40% of them will relapse within 5 years. In addition, studies have shown that the natural process of self-healing and healing of surgical wounds actually stimulates the diffusion of these residual tumor cells to the distal end of the body and begins new growth.
“The long-lasting anti-cancer effect produced by immunotherapy is very powerful, but the proportion of patients who can benefit from these drugs is far from satisfactory. In this study, we tried to determine if the tumor was removed, Giving an agonist before the surgical wound is closed can improve the effectiveness of tumor immunotherapy," Dr. Goldberg said.
To make the method work, the researchers believe they need to change the immune environment within the surgical wound. When the tumor is removed, the cancer cells and neighboring cells (including immune cells and connective tissue) will also be removed together. In the tumor microenvironment, cells, proteins, and other substances that prevent the immune system from attacking tumors are usually included. The removal of these components may trigger the immune system to attack cancer cells after surgery, but the vital anti-cancer immune cells and proteins. Also removed together. In addition, after surgery, the immune system is mainly focused on treating wounds, while reducing the defense of cancer cells. It is this "immunosuppressive" microenvironment that allows residual tumor cells to spread and grow in other parts of the body.
Dr. Goldberg said: "The goal of the new approach is to transform the immunosuppressive environment into an 'immune-stimulus' environment." That is, the immune system is in a state of attacking cancer cells at any time.
In this study, the researchers implanted a gel (one-inch inch, made of degradable sugar found in a human body) that was previously embedded in an immunotherapeutic drug into the tumor resection site for a longer period of time. During the time, the slow release of the drug stimulates dendritic cells (DCs) that train T cells to attack cancer cells anywhere in the body, even those away from the original tumor site.
Image source: A biodegradable hydrogel representing those used in the study. Credit: C. G. Park et al. , Science Translational Medicine (2018)
The decision to implant a gel during surgery is based on several considerations. Dr. Goldberg pointed out: "We believe that it is easier to eliminate a small amount of residual cancer cells by creating an immune-stimulated environment than to treat a complete primary tumor, and that primary tumors have many ways to evade immune system attacks." In addition, immunotherapy before surgery may have immune-related side effects. In addition, a previous study showed that immunotherapy may be less effective after surgery and after wound healing.
The researchers confirmed that this method successfully transformed the immunosuppressive state of the postoperative wound area into an immunostimulatory state. Compared with intravenous injection or direct injection into tumors, the mice treated with the gel administration method had a greatly improved cure rate and no side effects were observed. Dr. Goldberg said his team evaluated changes in body weight in these mice and the potential toxicity of the liver, kidneys and blood cells - none of which was observed.
The advantage of this treatment is also reflected in the long-lasting therapeutic effect. Three months after the mice were treated, the tumor did not recur. When the researchers injected new breast cancer cells on the other side of the original tumor site, the tumor did not recur. The researchers said that this is a signal that the immune system is still actively fighting cancer.
According to Goldberg, the ability of implantable gels to address any solid tumor that can be surgically removed will greatly increase the number of patients who may benefit from such potent immunostimulants. “The results of this study have greatly inspired us and hope that this technology will benefit patients in clinical trials in the near future.â€
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