Antibodies are naturally occurring proteins that help our body fight bacteria, viruses and cancer. Upon its release into the blood stream, an antibody can identify and bind a specific pathogen, and by doing so, it can neutralize the pathogen or “flag” it for attack by the immune system. Our body is able to generate antibodies against a virtually infinite number of targets, thanks to brilliant biological mechanisms developed throughout the course of evolution. Once a pathogen enters our body, our immune system conducts a high-throughput screen of all the antibodies it can generate (around 10 billion different antibodies). After the appropriate antibodies are selected, special white blood cells called B-cell lymphocytes enter a mass production phase in which large amounts of the selected antibodies are secreted into the blood stream “in search” of their specific target. The combination of diversity on the one hand and specificity on the other hand, makes antibodies a crucial component of our defense mechanism. This combination also makes antibodies an extremely popular platform among drug companies.
Harnessing the incredible mechanism by which antibodies operate as a basis for drugs has always seemed very promising. Understanding and controlling the natural processes which design and produce antibodies may enable the creation of “artificial” antibodies which recognize and “flag” a chosen target. Such targets might be cancer cells, harmful proteins or inflammation molecules. After years of trials (and errors), scientists have managed to manipulate the biological processes which lead to the formation of antibodies and develop therapeutic antibodies. Although the first therapeutic antibody was approved more than 20 years ago, the majority of therapeutic antibodies have hit the market only during the past 10 years. Therapeutic antibodies have proven effective at fighting cancer, especially in cases where conventional therapy fails: Out of the 21 marketed therapeutic antibodies, 9 are for the treatment of cancer.
Even more encouraging is that antibodies for cancer generally operate in a distinct mechanism from traditional chemotherapy or radiotherapy, so they can often be combined with traditional therapies to generate a synergistic effect. Without a doubt, cancer antibodies are one of the biggest breakthroughs in cancer therapy’s history. Examining any medium or large biotech company’s pipeline demonstrates how central antibodies’ place is in the pharma industry. It is hard finding a company without at least a hand-full of therapeutic antibodies in various stages of clinical development. Some companies preferred entering the antibody market by acquiring antibody-specialized companies (AstraZeneca’s acquisition of CAT)
Without underrating antibodies’ important position in the field of cancer therapy, there is still a lot of room for improvement. Cancer antibodies rarely cure the disease, especially in its more advanced stages, and the life expectancy benefit generally ranges from several months to several years. When it comes to solid tumors, which represent a tougher nut to crack (therapeutically speaking), the performance has been notably poor. Even though solid tumors consist the vast majority of cancer cases (lung cancer, breast cancer, colon cancer, etc.), out of 9 FDA-approved antibodies for cancer, only 3 target solid tumors (Herceptin®, Erbitux®, Vectibix®), with the rest aimed at non-solid targets.
As previously stated, antibodies are generally administered in combination with chemotherapy or radiotherapy in order to obtain optimal effects. When comparing the general characteristics of cancer antibodies like Herceptin® and Rituxan® with those of traditional therapies like Taxol®, Doxorubicin®, and radiotherapy, there are two obvious differences: The first one is the very high specificity antibodies possess compared to that of chemotherapy agents and radiotherapy. Both chemotherapy and radiotherapy are non- targeted therapies. Chemotherapy substances are usually distributed throughout the patient’s body while radiotherapy exposes large portions of the patient’s body to radiation. Antibodies, on the other hand, bind cancer cells and affect them almost exclusively, sparing normal cells.
The second difference is potency. Chemotherapy agents are very strong and toxic compounds, some of which are actually derived from deadly natural poisons. With numerous mechanisms of action, such as interference with DNA replication and cell division, chemotherapy agents are very effective against cancer tissues but also, to a lesser extent, harmful to healthy tissues. Antibodies operate in a different manner. By binding to cancer cells they can induce an immune response towards those cells or block growth and proliferation signals, but they are much less potent. It is therefore clear that the advantage of chemo/radio-therapy is the Achilles hill of antibodies and vice versa. This leads to the unbearable compromise doctors and caregivers have to make: On the one hand, they are limited in the amount of chemotherapy and radiation they administer, due to the severe side-effects. On the other hand, they can administer monoclonal antibodies which cause less side-effects, but cannot inflict enough damage on cancer cells.