Dr. Weeks’ Comment: Any old school pediatrician understands that childhood illnesses have risks, but they also have benefits. To understand the benefits of childhood illnesses think of them as training grounds for the developing immune system. Studies show that the more sterile the child’s environment, the weaker her or his immune system. Let your kids play in the dirt! When I was a young parentWhen I was a young parent I did with my parents did when I was a baby which is which is when a neighborhood child had measles when a neighborhood child had measles we brought all the uninfected children over to get exposed to the measles at a young age we brought all the uninfected children over to get exposed to the measles at a young age to enhance their immune response going into the future. As Nietzsche wrote in 1888 in his book of aphorisms, Twilight of the Idols, “Aus der Kriegsschule des Lebens.—Was mich nicht umbringt, macht mich stärker,” or in English “Out of life’s school of war—what doesn’t kill me, makes me stronger.” Can measles virus help protect you from cancer? Read on below.
Curr Top Microbiol Immunol. Published in final edited form as:Curr Top Microbiol Immunol. 2009; 330: 213–241. 19203112
Measles Virus for Cancer Therapy
Stephen J. Russell, M.D., Ph.D. and Kah Whye Peng, Ph.D.
Abstract
Measles virus offers an ideal platform from which to build a new generation of safe, effective oncolytic viruses. Occasional “spontaneous” tumor regressions have occurred during natural measles infections, but common tumors do not express SLAM, the wild-type MV receptor, and are therefore not susceptible to the virus. Serendipitously, attenuated vaccine strains of measles virus have adapted to use CD46, a regulator of complement activation that is expressed in higher abundance on human tumor cells than on their non transformed counterparts. For this reason, attenuated measles viruses are potent and selective oncolytic agents showing impressive antitumor activity in mouse xenograft models. The viruses can be engineered to enhance their tumor specificity, increase their antitumor potency and facilitate noninvasive in vivo monitoring of their spread. A major impediment to the successful deployment of oncolytic measles viruses as anticancer agents is the high prevalence of pre-existing anti measles immunity, which impedes bloodstream delivery and curtails intratumoral virus spread. It is hoped that these problems can be addressed by delivering the virus inside measles-infected cell carriers and/or by concomitant administration of immunosuppressive drugs. From a safety perspective, population immunity provides an excellent defense against measles spread from patient to carers and, in fifty years of human experience, reversion of attenuated measles to a wild type pathogenic phenotype has not been observed. Clinical trials testing oncolytic measles viruses as an experimental cancer therapy are currently underway.
Oncolytic Viruses
Viruses that replicate selectively in neoplastic tissues (oncolytic viruses) hold considerable promise as novel therapeutic agents for the treatment of human malignancies and many such agents are currently under investigation, both in preclinical studies and in human clinical trials.[1–4] The existence of viruses was not recognized until the turn of the 19th century, but ever since that time, they have continued to attract considerable interest as possible agents of tumor destruction.[5, 6] Clinical observations suggested that, given the right set of conditions, cancers would sometimes regress during naturally acquired virus infections.[5, 7–9] Clinical trials were therefore conducted in which a variety of different human and animal viruses were administered to cancer patients.[5, 10–14] Most often, these viruses were arrested by the host immune system and did not significantly impact tumor growth.[15] However, in a few immunosuppressed patients, the infection “took” and tumors regressed, although all too often, this was associated with unacceptable morbidities due to infection of normal tissues. Attempts to address the specificity problem continued throughout the 1950s and 1960s but the results, although encouraging, were not compelling, and with the advent of anticancer chemotherapy, the concept of using replication competent viruses as anticancer agents was largely eclipsed.[5] However, by the 1980s it was clear that even the combination of surgery, radiotherapy, and anticancer chemotherapy was failing to substantially impact cancer mortality and with the advent of modern virology accompanied by powerful reverse genetic systems, there came a resurgence of interest in oncolytic viruses.[16–19] During the past two decades, oncolytic virotherapy has reestablished itself as a respectable field of research and there are new numerous ongoing early phase clinical trials testing a wide variety of oncolytic viruses representing many virus families.[3, 20–26]