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2009 ). Following surgery to remove a part or whole of the tumor, the tissue specimen
is shipped frozen to Agenus, which prepares the vaccine and sends it back for intra-
dermal injection when the patient has recovered from surgery. It has been tested in
numerous patients in multiple cancers in clinical trials and approved in Russia as
Oncophage ® for the adjuvant treatment of kidney cancer patients at intermediate-
risk for disease recurrence. It has orphan drug designation from the FDA as well as
EMEA for kidney cancer and glioblastoma. Results of clinical trials of Prophage
show that:
- It is well tolerated
- Elicits tumor-specifi c T cell responses and innate immune response irrespective
of tumor type - Effi cacy is most signifi cant in patients with early-stage disease and low tumor
burden
Melacine
Melacine melanoma vaccine was developed by Corixa Corporation (now acquired
by GlaxoSmithKline) consists of lysed cells from two human melanoma cell lines
combined with an adjuvant that includes monophosphoryl lipid A and mycobacte-
rial cell wall skeleton, both of which activate the human immune system. Melacine
vaccine is approved in Canada but not in the USA. It is administered as a two-shot
vaccination delivered as four 6-month cycles, each consisting of 10 treatments fol-
lowed by a 3-week rest. Patients who respond are maintained on long-term therapy.
A randomized phase III trial of Melacine plus low-dose IFN-α2b in malignant
melanoma had an effect comparable to standard high-dose IFN-α2b but with less
toxicity (Ding and Wei 2007 ). Analysis of clinical benefi t following completion of
the data sweep in patients who were positive for expression of either Class I MHC
HLA A2 or C3 genes continued to show a highly statistically signifi cant clinical
benefi t of Melacine in terms of increased disease free survival. Patients with these
genes account for an approximate 60–70 % of all melanoma patients.
Patient-Specifi c Cell-Based Vaccines
Dendritic Cell-Based Vaccines
Dendritic cells (DCs), named after their long arms, comprise a system of leukocytes
widely distributed in all tissues. DCs are derived from bone marrow progenitors and
circulate in the blood as immature precursors prior to migration into peripheral tis-
sues. Within different tissues, DCs differentiate and become active in the taking up
and processing of antigens and their subsequent presentation on the cell surface
linked to major histocompatibility complex (MHC) molecules. Upon appropriate
stimulation, DCs undergo further maturation and migrate to secondary lymphoid
10 Personalized Therapy of Cancer