Textbook of Personalized Medicine - Second Edition [2015]

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Personalized Cancer Vaccines


There are several types of cancer vaccines, which include nucleic acid-based, MAb-
based and cell-based vaccines. Various types of cells are used including tumor cells
and dendritic cells. Combination of different methods and genetic modifi cation of
cells are also used. Personalized vaccines may be antigen-specifi c or tumor-derived,
but patient-specifi c vaccines may be a combined approach. Most of the personalized
cancer vaccines are cell-based and these were the earliest forms of personalized
medicine (Jain 2010 ). A true personalized vaccine is one in which patient’s own
cells are used.


Antigen-Specifi c Vaccines


Antigen-specifi c approach may generate an antigen-specifi c response even when
the tumor antigens are not known. Currently the scope of cancer immunization is
limited because most of the vaccines have targeted antigens that are restricted to a
subset of patients. Functional genomics and proteomics will enable molecular
characterization of whole transcriptomes and proteomes of cancer cells, thereby
also identifying potential new targets for cancer immunotherapy. Based on funda-
mental immunological knowledge, the most promising approach would be
patient-tailored.


Active Immunotherapy Based on Antigen Specifi c to the Tumor


Active immunotherapy is focused on overcoming the limitations of the immune
system and directing it to mount an attack against cancer cells. Activating the
immune system begins with the selection and modifi cation of a tumor antigen spe-
cifi c to the cancer (e.g. prostatic acid phosphatase found in ~95 % of prostate can-
cers), which is produced using recombinant DNA technology.
The lead product in this category is sipuleucel-T (Provenge™, Dendreon
Corporation), which targets prostatic acid phosphatase. A proprietary technique is
then used to isolate antigen presenting cells taken from a cancer patient, which are
combined with the modifi ed antigen using Antigen Delivery Cassette™. The acti-
vated cells are then re-administered to the patient to stimulate T-cells to recognize
and attack cancer cells that contain prostatic acid phosphatase. Sipuleucel-T has
been approved by the FDA for the treatment of patients with early-stage and
advanced prostate cancer. In clinical studies, patients typically received 3 infusions
over a 1-month period as a complete course of therapy. Integrated results of two
randomized trials demonstrate a survival benefi t for prostate cancer patients treated
with sipuleucel-T with a modest toxicity profi le (Higano et al. 2009 ). A phase III
clinical trial, IMPACT (IMmunotherapy for Prostate AdenoCarcinoma Treatment)


10 Personalized Therapy of Cancer
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