Shepherding Therapeutic Cancer Vaccines through Clinical Development | Page 3

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Developing novel
therapeutics is an
uncertain
enterprise in any
disease state, but
developing a
whole new type of
therapeutic
represents an
order of
magnitude
greater
challenge.

are generated from the patient’s own tumor cells, which are modified and
killed. In contrast, allogeneic (off-the-shelf) vaccines are based on antigens
common to all or most cases of a particular type of tumor, such as the gp100
peptide found on melanoma cells. An inherent challenge in developing a
therapeutic cancer vaccine is that tumor cells are self-derived, subverting the
immune system’s main function in targeting non-self cells and proteins.
However, tumors do express specific antigens, or cell surface proteins, that
distinguish them from normal cells. Yet tumors can be antigenic, meaning they
have the potential to be recognized as foreign, without being immunogenic,
meaning actually inducing an immune response. And conditions in the
microenvironment surrounding a tumor can affect the ability to mount an
immune response.
Cancer is a disease of genetic origin, where the DNA within an individual cell
accumulates mutations. If the mutations occur in genes that regulate growth
and division, the cell and its offspring can divide and become numerous in an
unregulated fashion. In recent years, characterizing mutations within a tumor
has become possible. In most adult cancers, including breast, ovary, colorectal,
pancreas, and glioma, there are between 1,000 and 10,000 somatic mutations
(Greenman et al, 2007; Wood et al, 2007). While the cells within a tumor have
common mutations, cells from different tumors—even in the same type of
cancer—have an infinite combination of mutations. “Cancers are all unique;”
says Michael Hanna, PhD, founder of Vaccinogen, Inc. “One patient’s cancer is
unique from another’s.” These differences in mutations, which create different
antigen patterns on the surface of tumor cells, can make design of allogeneic or
off-the-shelf therapies challenging.

Prior Failures and Lessons Learned
Developing novel therapeutics is an uncertain enterprise in any disease state,
but developing a whole new type of therapeutic represents an order of
magnitude greater challenge. Thus, the story of therapeutic cancer vaccine
development has been a story of challenges; some pertaining to the complexity
of cancer treatment, others to evaluating a therapy in a severely diseased
population, others to industrial paradigms of manufacturing and mass
production, and ultimately challenges related to a regulatory paradigm
developed around small-molecule and antibody therapeutics.

Clinical endpoints based on tumor size. One of the most important
lessons learned in the last ten years is that the efficacy of therapeutic vaccines
should not be measured by the same standards as those for chemotherapeutic
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