Cancer is a constellation of diseases united by one deadly trait: cells in regions as diverse as bone marrow, brain or lung begin to divide uncontrollably and form tumors. Loss of growth control and invasive, metastatic activity that often follows are primarily caused by mutations in genes that normally keep these processes in check. Genetic damage is caused by carcinogens (such as tobacco smoke or asbestos), inheritance (as in the case of inherited “predispositions” to breast or ovarian cancers), or simply random mistakes made by the cellular machinery that copies DNA when cells divide.
Early treatments relied primarily on tumor eradication by surgery or radiation. Since the war on cancer began in the 1970’s, drugs to complement those approaches emerged from discoveries made in basic research labs and then developed in drug or biotechnology companies. Many of those success stories report treatments for specific cancers, among them antibodies that block HER-2 receptors on breast tumors or others that recognize B cell receptors dotting lymphoma cells. Despite the effectiveness of these approaches, cancers still claim about a half a million American lives yearly and remain the second leading cause of death in the U.S. behind heart disease. Thus the demand for novel pharmaceuticals continues, a demand that can only be met when we understand the basic biology of a cancer cell.
Rallying the immune system
Recently, a new way of thinking about stopping cancer has emerged in labs of immunologists, particularly those studying T cells, which normally attack “foreign” cells or cells harboring bacteria or viruses. Scientists initially found that T cell responses to tumor cells were unusually sluggish. In the last decade they discovered why: Inhibitory molecular signals emitted from a tumor or its environment undercut the immune response, putting tumors under a virtual immunological invisibility cloak.
Those discoveries form the basis of an entirely novel approach known as “immunotherapy”, lauded by the prestigious journal Science as the “breakthrough of the year” for 2013. Its advocates posit that it is possible to rouse lethargic immune cells to mount an anti-tumor attack using pharmaceuticals, antibodies, or even infusions of lymphocytes or stem cells. Now, scientists at LJI and worldwide, many of whom may have begun their careers studying infection or inflammation, are refining immunotherapy-based strategies as a powerful weapon in the arsenal against cancer.
One LJI team, for example, discovered how to convert helper T cells, which normally assist in or suppress an immune attack, into more aggressive killer T cells capable of recognizing and then neutralizing tumors. Others are partnering with clinicians to develop and test personalized vaccines to boost a patient’s anti-tumor response. Still others are evaluating factors that could pharmaceutically dismantle the so-called “immune checkpoint”, which amounts to a molecular brake applied to anti-tumor T cell responses.
Cancer researchers generally agree that there is no single way to eradicate most tumors. Instead, the current consensus is that effective approaches will be multi-pronged and patient-specific, integrating surgery or radiation when appropriate with oncogene-targeting chemotherapies and interventions that put teeth in a patient’s immune response. The advent of the latter puts LJI, with historic expertise in the immune response to allergens and infections, front and center.