Blood, 1 October 2001, Vol. 98, No. 7, pp. 1999-1999
Myeloma gets the measles
Co-opting micro-organisms as anticancer agents is not a new
concept, with multiple agents investigated since the beginning of the
20th century for their potential to kill tumor cells with some degree
of selectivity or to redirect immune responses against malignant cells.
Other than the instillation of bacillus Calmette-Guérin for
superficial bladder cancer, these approaches were eventually abandoned
because of lack of controlled evidence for antitumor responses,
significant toxicity, and a shift to pharmacologic therapies. But over
the past 5 years, a number of anticancer attenuated or engineered
viruses have begun to be developed, based on a better understanding of
both the viruses and the target tumors. An engineered adenoviral mutant
(ONYX-015) has shown some activity against head and neck tumors in
phase 1 and 2 clinical trials.
Peng and colleagues (page 2002) describe a very exciting property of
the measles virus, namely efficient and selective killing of human
myeloma cells. They have chosen to use the Edmundston-B live attenuated
vaccine strain, given safely to hundreds of millions of people.
Exposure of myeloma cell lines and primary myeloma plasma cells to this
virus resulted in efficient infection, replication, multinucleated
syncytia formation, and cell death, in contrast to lack of effects on
human peripheral blood lymphocytes. Intratumoral or intravenous
injection of the virus resulted in marked shrinkage of already
established human myeloma tumors growing in immunodeficient mice. There
was no systemic toxicity, but mouse cells do not have the receptor for
the measles virus. Prior human experience using the virus as a vaccine
involved lower doses administered subcutaneously. One potential problem
with administration of an attenuated measles virus, namely,
pre-existing immunity from prior vaccination, may be less of an
obstacle in myeloma patients, known to have significant defects in
mounting specific antibody responses.
The mechanisms for the selective killing of myeloma cells by this virus
are unknown but could include increased uptake into tumor cells due to
higher receptor levels, enhanced intracellular viral replication, or
impaired antiviral responses of tumor cells. Further experimentation is
in progress to answer these questions. The virus is also attractive
because it can potentially be redirected to alternative tumor types by
modification of a surface H-glycoprotein or enhanced in antitumor
properties by addition of other genes to the measles genome. Meanwhile,
clinical testing of this virus in myeloma patients would seem justified
in the near future after completion of more extensive toxicity testing.
Cynthia E. Dunbar
National Institutes of
Health
