Vaccine that combines a synthetic bacterial DNA sequence and melanoma antigen shows promise in phase I trial
A cancer vaccine that combines a commercially
produced bacterial DNA sequence with a peptide antigen found on
melanoma cells has shown promise in a phase I trial, according to
an article in the February issue of the Journal of Clinical Investigation.
The Swiss-American team found that the CpG
7909 DNA sequence (ProMune-, Coley Pharmaceutical) is safe and increases
the immune system’s ability to recognize and destroy cancer cells.
The Phase I study was conducted by the Lausanne Branch of the Ludwig
Institute for Cancer Research in the framework of the international
Cancer Vaccine Collaborative, a partnership established by the New
York-based Cancer Research Institute and the Ludwig Institute.
“What we’re doing is testing a novel adjuvant,
a compound that stimulates the immunological response to a vaccine,
which is essentially tricking the immune system into thinking the
vaccine is a bacterial infection,” said lead author Dr. Daniel Speiser.
“The immune system mounts a response against the peptide antigen,
the cancer-specific target, in the vaccine, and thus also against
the antigen on the cancer cells.”
The vaccine, combining the CpG 7909 adjuvant
and Incomplete Freund’s Adjuvant with a synthetic peptide from a
melanoma antigen known as Melan-A/MART-1, induced CD8+ T cells that
specifically recognized cells displaying Melan-A/MART-1 on their
surface.
This T cell response occurred in all eight
patients in the trial. Responses were one order of magnitude higher
than those observed in eight patients who received the Melan-A/MART-1
antigen with IFA but without CpG 7909 in previous studies.
According to Dr. Jill O’Donnell-Tormey, the Executive Director of
Cancer Research Institute, the trial is part of a systematic, coordinated
vaccine development approach that compares single vaccine variables
in parallel. “We’ve identified many cancer antigens, and the challenge
is to determine which cancer vaccine compositions induce a strong
and sustained immune response against particular antigens. The results
from this trial represent a substantial step forward in this regard.
“This conclusion is justified because we
are using reproducible immunological monitoring, allowing a more
accurate comparison of the effects of CpG 7909 in this trial with
the results of several other adjuvants that have been tested in
other trials. By comparing single variables in parallel we believe
we can develop effective cancer vaccines in a much shorter time
than the conventional approach of trying variables sequentially.”
Clinical research sites are located in Australia,
Belgium, Germany, Japan, Switzerland, the United Kingdom, and the
USA.
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