The Achilles heel of cancer
Antibodies deprive cancer cells of protection from the immune system
Researchers at Stanford University, working under the leadership of Professor Irving Weissman, have developed antibodies that significantly reduce in size or completely destroy human tumors transplanted into mice.
In an earlier study, the authors found that CD47 protein is usually expressed on the surface of circulating hematopoietic (hematopoietic) stem cells to protect these cells from macrophages. Macrophages move around the body in search of infectious agents or abnormally altered cells, but sometimes they make mistakes in choosing a victim. The presence of CD47 protein on the surface of the macrophage-absorbed cell causes it to release the mistakenly captured victim.
It also turned out that some tumors, especially those affecting the hematopoietic system of leukemia and lymphoma, borrowed this defense mechanism. In 2010, the authors demonstrated in a mouse model that blocking the CD47 protein with special antibodies used in combination with antibodies of another type that stimulate the instinct of macrophages to destroy invaders cures non-Hodgkin's lymphoma.
As part of their latest work (PNAS, The CD47-signal regulatory protein alpha (SIRPa) interaction is a therapeutic target for human solid tumors), the researchers found that the phenomenon they discovered is extremely common among solid tumors. To do this, they analyzed the expression of CD47 protein on cells of surgically removed samples of various human tumors, including ovarian, breast, colon, bladder, brain, liver and prostate cancers. It turned out that almost all tumors are characterized by high (on average 3 times higher than on healthy cells) expression of CD47 protein. In addition, a higher expression of CD47 on malignant cells corresponded to a worse prognosis of the course of the disease in humans.
After that, the scientists implanted cells of different types of human tumors into the corresponding organs of mice, and after the tumors were implanted (after 2 or more weeks), they injected antibodies against CD47 into the animals.
As a result, most of the implanted tumors began to shrink in size, while some of them completely disappeared within a few weeks of antibody therapy. The authors also note that in cases of particularly aggressive tumors, the introduction of antibodies blocked their metastasis.
In one case, the antibodies cured five animals that were injected with cells from the same sample of human breast cancer. After the tumors disappeared, treatment was discontinued, and during four months of follow-up, no signs of tumor recurrence were detected in the mice.
However, despite the impressive results, antibodies against CD47 are not a universal remedy for cancer. In a group of animals injected with breast cancer cells from another patient, no positive effects of therapy were observed.
Weissman emphasizes that in order to optimize therapy based on the introduction of antibodies against CD47, it is necessary to thoroughly understand the interaction between macrophages and tumor cells and develop methods for attracting more of these cells to the tumor zone. He suggests that the effectiveness of the method can be improved by preliminary surgical removal of the tumor or radiotherapy. Another possible option is the use of additional antibodies that stimulate the ability of macrophages or other immune cells to destroy malignant neoplasms.
In general, the researchers are very encouraged by the results obtained and plan to conduct clinical trials of their approach to antitumor therapy over the next two to three years.
Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru based on the materials of Stanford Medical Center:
Single antibody shrinks variety of human tumors transplanted into mice, study shows.
27.03.2012