restricted access Chapter 5. Monoclonal Antibodies and Other Magic Bullet Therapies
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151 CHAPTER 5 Monoclonal Antibodies and Other Magic Bullet Therapies We’ve come a long way in lymphoma treatment over the past fifty years. The majority of people with Hodgkin lymphoma can now be cured, and they will move on from their brush with death to have normal, healthy lives. Many people with aggressive NHL and some with indolent NHL can now be cured as well. But we still have a long way to go. A substantial minority of people with Hodgkin lymphoma will not be cured, and a substantial minority of those who are cured will experience serious long-term side effects from the therapy . Similarly, about half of those diagnosed with advanced-stage aggressive NHL will be cured, but half won’t. Many of us will experience dangerous, debilitating, or distressing long-term side effects from the therapy that saved our lives. And for the majority of people with low-grade lymphoma, the disease is still incurable. Until all lymphomas can be reliably cured, with little danger of long-term toxicity from the treatment, we cannot afford to be complacent. Fortunately, cancer research continues to push forward the range of available therapies, and right now we’re poised on the brink of some dramatic breakthroughs. Lymphoma therapy is already distinctly different from when I was diagnosed . Advances in the treatment of NHL during the 1990s were nearly as dramatic as the advances in treating Hodgkin lymphoma some forty years ago. Moreover, the American Society of Clinical Oncology named the transformation of chronic lymphocytic leukemia treatment by the monoclonal antibodies obinutuzumab and ofatumumab and the targeted chemotherapy drugs ibrutinib and idelalisib as their clinical cancer “Advance of the Year.” U 152 Treating Lymphoma We can hope that new advances will continue this encouraging trend and that therapies for those forms of lymphoma that are now curable continue to evolve in the direction of becoming less and less dangerous and unpleasant. This chapter describes some of the newer approaches to treating lymphoma . The treatments I discuss in this chapter are based on new types of anticancer therapy. These are directed therapies based on advances in our understanding of cancer or of the means our bodies use to fight disease. They differ from the older forms of cancer therapies in their selectivity against cancer cells. Many of these newer therapies promise to act as the longsought “magic bullets” that shoot down cancer cells but leave the rest of the body untouched. These directed therapies include immunological therapies (or immunothera‑ pies), which involve the immune system, and therapies that depend on a detailed understanding of biological mechanisms underlying cancer. I discuss some directed therapies that are now in common use against lymphoma, such as monoclonal antibodies, as well as some that are still experimental. Over the past thirty years, our understanding of immunology, the branch of biology concerned with the function of the immune system, has really exploded. Several of the new approaches to cancer therapy in general (and lymphoma in particular) make use of this knowledge. And it somehow seems appropriate that the power of the immune system itself should be harnessed to fight these immunological cancers. Immunotherapies Monoclonal Antibodies As discussed in more depth in Chapter 10, B cells and plasma cells, which are the completely differentiated form of the B cell, are considered part of the humoral immune system. Their immunological actions are mediated by anti‑ bodies, proteins secreted into the blood that recognize and bind to antigens. Antigens are defined as substances that can stimulate the production of antibodies . In general, they are substances that the immune system recognizes as foreign (and therefore potentially dangerous). Antibody-antigen interactions are very specific: an antibody that recognizes a particular antigen (say, a protein on a poliovirus) won’t recognize any other. When a secreted antibody recognizes and binds to its antigen, it sets a series of events into play. These are designed to neutralize and get rid of the Monoclonal Antibodies and Other Magic Bullet Therapies 153 V antigen. When antigens are part of a foreign cell, antibodies can flag that cell as a target for other components of the immune system to destroy. There are various ways in which the immune system can act against cells that have been targeted by an antibody. In some cases, the bound antibodies trigger a direct attack by other cells in the immune system. Macrophages, neutrophils, and natural killer cells can all recognize bound antibodies. When an antibody signals these cells that a...