Louisville Medicine Volume 69, Issue 9 - Page 20

INVASION BY THE MOB OF mAbs Vasudeva Iyer , MD

INVASION BY THE MOB OF mAbs Vasudeva Iyer , MD

The word “ mob ” might remind many of us of the disturbing events that occurred in Washington , D . C . on Jan . 6 , 2021 , but this is an article about a different type of mob - which can significantly benefit the medical field . I ’ m referring to the drug mob that has revolutionized the therapeutic universe : the monoclonal antibodies ( mAbs ).

It was 35 years ago in 1986 that the FDA approved the very first monoclonal antibody , muromonab , for combating the rejection of kidney transplants . Since then , more than 100 mAbs have been approved for treatments including targeted drug therapy and many more are in the pipeline . The recent emergency authorization of several mAbs for treating COVID-19 infections has propelled them into the limelight . To understand their role in the COVID-19 pandemic , I was tempted to look into the history of discovery of these drugs .
B cells , a type of lymphocytes , oversee production of antibodies , the humoral part of adaptive immunity . They produce antigen-specific immunoglobulin ( Ig ), which are the antibodies that fight invading pathogens . A specific antigen can stimulate the B cell to multiply and form a clone of cells producing precisely identical antibodies ( monoclonal antibodies ). Early attempts to produce these antibodies in the laboratory from B cells in large quantities were hampered by the short lifespan of these cells . In 1975 , George Kohler and Cesar Milstein at the MRC laboratory of molecular biology in Cambridge , UK discovered that fusing a type of cancer cell ( derived from myeloma ) with the B cells will “ immortalize ” the resulting hybrid cell ( hybridoma technology ) and provide a source for significant quantities of monoclonal antibodies . Since then , lab techniques have been improving steadily leading to production of humanized / human mAbs . They have managed to revolutionize the field of immunology by providing tools for advanced immunohistochemistry and diagnostic tests ; they provide reliable probes of protein structure and their identification in vivo . Above all they have become the cutting edge drugs in managing a wide variety of diseases , ranging from cancer to migraine . Kohler and Milstein shared the 1984 Nobel prize in physiology or medicine with Niels K . Jerne for their roles this groundbreaking achievement .
Although the first mAb drug was intended for prevention / reversal of kidney transplant rejection , mAbs have since become indispensable for treating a wide variety of diseases that affect almost every system in the body . We use mAbs in the treatment of various forms of cancer including uterine , breast , urothelial , bladder , colorectal , gastric , lung , melanoma , glioblastoma , as well as lymphomas and leukemias using target-specific mAbs . There are many ways these drugs are designed to attack cancer cells . Some block angiogenesis necessary for tumor growth while others coat cancer cells so that they can be detected and destroyed by the body ’ s own immune apparatus . Another mechanism is blocking immune system inhibitors ( check point inhibition ), leading to immune-mediated destruction of cancer cells . MAbs can also be used to deliver chemotherapeutic agents selectively to the cancer cells . In the field