Antibody Targeting Program
LICR has generated numerous antibodies that specifically target cancer cells, but not normal cells, in preclinical testing. Some of these antibodies are being developed into therapies that can be used to activate the immune system against cancer cells, or can be used to deliver radioisotopes or toxins directly to cancer cells.
Introduction
LICR’s research efforts in cancer immunology have resulted in the generation of numerous antibodies that have the potential to be developed into effective cancer therapies. Antibodies are proteins that are a vital component of the body’s immune system. Whilst circulating in the blood, antibodies recognize and bind to antigens that are displayed on the surfaces of cells. The antibody bound to the antigen on the cell surface marks the cell for recognition and destruction by the immune system. LICR scientists are world-leaders in the field of cancer antigen identification and characterization, and were the first to clone a human cancer antigen (see Cancer Antigen Discovery Program).
A key component of the LICR approach to developing antibodies for successful targeted therapy is that scientific investigations continue throughout the clinical trial process. In initial clinical trials in the field of immunotherapy, antibodies showed positive effects against cancer, but failed to demonstrate any change in traditional endpoints, such as tumor regression. Now, by monitoring a broad range of antibody properties in patients, LICR researchers are determining which antibody characteristics are best suited to attack the disease, leading to the development of more effective treatments.
So far, LICR has completed over twenty clinical trials of antibodies, and many more are ongoing. In order to perform experiments and trials at this level, LICR has developed an in-house Biological Production Facility, and maintains its own regulatory and monitoring capabilities. Antibodies take considerable time to develop. But after of years of study, several are showing increasing promise [LICR Clinical Trials].
Targeted antibodies can be employed as cancer therapies in several ways. They can:
- Bind to cancer-specific antigens and prompt a local immune response, known as antibody-dependent cell-mediated cytotoxicity (ADCC), against the tumor;
- Bind to cancer-specific antigens and sensitize tumors to cytotoxic drugs;
- Bind to cancer-specific antigens and deliver cytotoxic (‘cell killing’) molecules such as toxins or radioisotopes (‘radioimmunotherapy’);
- Block specific signal transduction receptors to prevent cancer cells from growing or dividing, or induce apoptosis (programmed cell death).
There are several components of the LICR Antibody Targeting Program:
Antibody Characterization
The detailed antibody characterization performed by LICR not only increases the chance that the antibody will be therapeutically beneficial, it also decreases the risk that the antibody will have harmful side-effects.
Antibody Engineering
Some characteristics of an antibody, which may prevent its use, or reduce its efficacy as an immunotherapy, can be altered through genetic engineering. Thus the immunogenicity of an antibody (its propensity for being destroyed by the immune system before it can act) can be reduced or eliminated, the affinity (strength of binding) of the antibody for its antigen can be enhanced, or the production of the antibody in a Biological Production Facility can be increased.
