241found that sipuleucel-T reduced the risk of death by 22.5 % compared with a
placebo. The treatment extended the lives of patients by 4–5 months and 33 % per-
cent of patients with advanced disease were still alive 3 years after treatment with
sipuleucel- T. Although sipuleucel-T is prostate-specifi c, the underlying principle
may be applicable to other cancers and it may be used in combination with chemo-
therapy. Several MAbs are in preclinical development, which are designed to recog-
nize a specifi c antigen present on tumor cells but not on healthy cells and bind to
that antigen to cause the death of the tumor cell. By this approach healthy cells
should not be affected, reducing or eliminating the harsh side effects of many con-
ventional cancer therapies.
GlaxoSmithKline is developing MAGE (melanoma antigen gene)-A3, a tumor
antigen-based patient-specifi c vaccine for melanoma and it has undergone phase II
clinical trials. Distinct gene expression profi les have been identifi ed on pretreatment
biopsies that are associated with a positive or negative clinical outcome, and this
might be useful as a predictive biomarker for clinical trials of melanoma vaccines
(Gajewski et al. 2010 ). Phase II clinical trials have demonstrated a clinical benefi t
by postoperative vaccine with MAGE A3 in non-small cell lung cancer and in stage
IV melanoma, which have led to the current phase III trials (Peled et al. 2009 ).
Tumor-Derived Vaccines
Although cancers may arise by common mechanisms, i.e. through mutations in
genes implicated in cell transformation (i.e. p53, ras), they undergo additional ran-
dom mutations in other genes. These mutations lead to expression of foreign anti-
gens, forming a molecular “fi ngerprint” that uniquely characterizes the patient’s
tumor. Because mutations are generated randomly, the antigenic fi ngerprint of one
person’s cancer can never be duplicated in another person’s cancer. Thus individual
cancers within the same pathological category are antigenically distinct. This fun-
damental property requires that each patient’s immune system be trained to recog-
nize that patient’s specifi c cancer. This is the basis of manufacture of cancer
immunotherapeutic from each patient’s own tumor tissue. Another approach is to
identify as many candidates as possible for tumor-associated T-cell epitopes in indi-
vidual patients. Expression profi ling of tumor and normal tissue can be performed
to identify genes exclusively expressed or overexpressed in the tumor sample.
Mass spectrometry enables characterization of several different major histocom-
patiblity complex (MHC) ligands from the same tumor sample. Combining these
two analytic tools, it is possible to propose several candidates for peptide-based
immunotherapy. This integrated functional genomics approach can be used for the
design of antitumor vaccines tailored to suit the needs of each patient.
Whole tumor cells of the patient, rendered safe by irradiation and mixed with an
immunological adjuvant, were one of the earliest forms of personalized cell therapy.
This approach avoids the need for tumor antigens to be identifi ed before treatment
and allows all of the relevant antigens to be included in the vaccine. Initial clinical
Personalized Cancer Vaccines