LD22-4 is an 86 amino acid protein that was generated from a larger naturally occurring human protein using genetic engineering techniques. LD22-4 has a unique mode of action, inhibition of cell migration; it inhibits cell migration by up to 90%, it is effective against a variety of cell types, and it works under a variety of conditions.
Cell migration and Disease: Cell migration is required for the onset and progression of many diseases including eye diseases and cancers. For solid tumors to grow, tumor cells need to migrate away from the center of the tumor. As cells migrate away, they generate empty space for other cells to divide, increasing the number of cells within the tumor core and eventually increasing tumor size and mass. Cell migration also is essential for the abnormal blood vessel growth. Abnormal blood vessel growth causes macular degeneration and it is important for tumor growth. Before new blood vessels can be formed, endothelial cells in existing blood vessels must divide and migrate into a new area. Stop the endothelial cells from migrating and new blood vessels cannot form. The rationale for the development of LD22-4 as a therapeutic is based on our belief that diseases can be controlled by inhibiting the migration of the cells that cause the disease.
LD22-4 has been tested for its ability to suppress tumor formation and blood vessel growth in several models.
FIGURE 1
MCF7 mammary carcinoma cells derived
tumor 15 days after implantation
The effect of LD22-4 on tumor growth was tested in mice with tumors derived from different types of cancers; mammary, lung, and prostate. The results of these experiments supported our hypothesis that LD22-4 was able to inhibit tumor growth in the animal. Two examples are given. (See Figure 1) Tumor cells from a human mammary tumor were implanted into mice. Some mice were treated with LD22-4 and others were not. After 15 days, a dramatic difference in tumor size was observed; tumor not treated with LD22-4 was much larger than the tumor treated with LD22-4 (80% smaller).
FIGURE 2
Fluorescently-labeled Lewis Lung
carcinoma 48 hours after implantation
Another experiment was performed with tumor cells derived from lung tumors. (Figure 2) In this case, the tumor cells were allowed to grow for only 48 hours and then the size of the tumor was measured. After 48 hours the tumor that was not treated with LD22-4 (control) had expanded 4 times while the tumor treated with LD22-4 remained the same size as the original tumor (0 hour).
FIGURE 3
LD22-4 affects on blood vessel growth
LD22-4 is also effective against blood vessel growth in the animal.
(Figure 3) When a gelatin-like material containing prostate tumor cells alone or prostate tumor cells with LD22-4 is injected under the skin of a mouse and blood vessel growth is measured after 7 days, blood vessel growth is dramatically reduced in the presence of LD22-4 (shown by the decrease in the red color). The tumor cells used in this experiment produce a variety of factors that promote blood vessel growth. These results provide direct evidence that LD22-4 is effective in the presence of a complex mixture of compounds that stimulate blood vessel growth.