Monoclonal Antibody Therapy
Humanized monoclonal antibodies have changed the cancer treatment landscape over the past decade. Both in hematologic and solid tumors, antibodies have become an integral component of treatment regimens that have improved and extended the lives of cancer patients. In addition, antibodies have been able to improve efficacy while not significantly adding more toxicity. In solid tumors, Avastin® in combination with chemotherapy is becoming a standard of care in colorectal, non-small cell, breast, and renal cancers. The traditional challenge in oncology drug development has been that incremental increases in efficacy have been accompanied by significant increases in toxicities as the number of chemotherapy drugs being combined became unwieldy. Antibodies have overcome this challenge by providing significant increases in efficacy with less toxicity, due to their targeted nature.
Today, antibodies have been developed to treat an increasing number of cancers that affect a larger proportion of patients and make a significant contribution to overall or disease-free survival as part of a combination regimen with established cytotoxic chemotherapies. The vast majority of antibodies are given as part of a combination chemotherapy regimen to realize their full potential. Enhancement approaches are designed to create more potent antibodies that work better in combination or possibly as single agent therapy. Companies are pursuing three types of enhancements to antibodies in search of improved product profiles. These enhancements include more precisely targeted antibodies, conjugated antibodies, and bi-specific antibodies. The enhancements all have a common goal of improving upon the efficacy seen with current antibody approaches without significantly increasing side effects.
Companies are refining or improving how antibodies bind to their targeted antigens. It is the hope that these more precisely targeted and more tightly binding antibodies will have increased efficacy. Companies are also seeking to increase the cancer cell killing capability of antibodies by linking or conjugating them to existing chemotherapeutics, radioisotopes or other cancer killing agents. While initial attempts to develop effective conjugated antibodies in the 1980’s and 1990s’ produced few successes, more recent efforts incorporating better linker technologies and better cancer killing agents are showing significant promise in clinical trials. In some cases, a disease process may involve more than a single protein biological pathway. Companies are responding to this biological complexity by developing antibodies known as bi-specific antibodies that are capable of binding two or more sites. The belief is that the bi-specific antibodies can be more effective because they block multiple biological pathways causing the disease state.
Monoclonal antibodies are generally given intravenously (injected into a vein). Compared with side effects of chemotherapy, the side effects of monoclonal antibodies are usually mild and similar to an allergic reaction. If they do occur, it is most often while the drug is first being given. Possible side effects can include: fever, chills, weakness, headache, nausea, vomiting, diarrhea, low blood pressure and rashes. Some monoclonal antibodies also have effects that are specific to the antigens they target.