Designing a Hyperstable Antibody with
Cell-penetrating Peptide for Intracellular Targeting
Therapeutic antibodies are currently used in many different fields of medicine to treat severe conditions such as cancer and immune diseases. These conventional therapeutic antibodies target antigens outside the cell membrane, triggering immune responses, and redirecting neutralization.
Unfortunately, such antibodies are restricted by their inability to enter the cell’s intracellular environment. In order to target intracellular proteins like Ras that could lead to the formation of cancerous tumors, we made scFv(Ras), which is an engineered form of scFv(F8) made to target the Ras protein by grafting antigen-binding sites of the anti-Ras antibody. This approach to cancer therapy aims to disable specific mutant antigens in the cell’s intracellular environment. Unlike conventional cancer therapy that aims to kill the cancerous cells in numbers, the scFv(Ras) compromises individual protein interaction within the cell. The method is comparatively effective and less lethal on surrounding normal cells caused by cytotoxicity. The target promising specificity and binding affinity of scFv(F8) justifies the therapeutic possibilities of scFv(Ras) while the technology widens the specific target mutant antigens for effective cancer treatment. The protein-protein modeling of human and mouse Ras is expected to be similar, considering the likeness of the Ras protein sequence once aligned. With more research, such treatments could be applied to animal testing for practical use to cancer patients, our end users.
Some challenges that we inevitably have to consider are the limitations of the method. The CPP tagged scFv(Ras) method is still very novel and requires more research to be done in order to be used in the real world. For example, when the antibody is injected into the body, safety issues may occur due to the angiogenesis characteristic of cancer. While the target-specific antibody will successfully reach the comprehensive mass of cancer cells through the blood vessels that run within the tumor, it can also mean that the antibody will affect normal cell activity of blood vessels or those cells close to the blood vessels. To mitigate the possible side effects, local administration of the antibody with the optimal dose and concentration of the antibody found through mathematical modeling will be crucial in developing the novel cancer therapeutics a step further. Also, we need to consider whether it is cost-effective in order to commercialize it.