Download File - JOHN J. HADDAD, Ph.D.

Personalized Cancer Vaccines 71
patients’ own cancers. Pramod Srivastava, Professor of Immunology and
Director of the University of Connecticut Cancer Center explains, “A cancer cell
can host millions of mutant peptides. Each time a cell divides, it probably has
about somewhere between 6 and 60 mutations” (16).
The personalized vaccines have the opportunity to present to the host
immune system the entire repertoire of the mutated peptides (antigens capable of
triggering immune system response) resulted from the degradation of encoded
proteins. The vaccines prepared from patient’s own tumor have the advantage of
possibly being more immunogenic, exposing the host immune system to a perceived
“foreign” large number of muted peptides including those antigens that
researchers have not yet recognized.
Another approach in personalized cancer vaccines is the dendritic cell–
based therapy. Patient’s dendritic cells (DC) are stimulated ex vivo through
exposure to tumor-cell lysate, fusion with tumor cells, infected by virus containing
a gene or exposure to purified peptides. A single or a few peptides from
cancer-specific antigens can be used to pulse the patient’s own DC. Given back
to the patient, DC will present the tumor antigens to the T cells in the effector
arm of the immune system (17).
In contrast to personalized vaccines using patient’s own tumor to derive a
large repertoire of antigens that DC load in vivo, DC vaccines are using patient’s
own blood to process autologous DC that are loaded in the laboratory with
allogeneic tumor antigens expressed by the majority of tumors in a given type of
cancer or on a variety of cancers.
Whether they are based on cancer cells, purified proteins, or live immune
cells, most therapeutic cancer vaccines generally aim to activate the branch of
the immune system that can directly target and specifically kill cancer cells.
Therapeutic cancer vaccines are based on the principle that, given the right
conditions, the human immune system is capable of generating an effective
antitumor immune response.
CLINICAL DATA IN PERSONALIZED CANCER VACCINES THAT
REACHED PHASE 3 CLINICAL TRIALS
One of the shared and clear advantages to cancer vaccines is the excellent safety
profile, which makes their use in the adjuvant or earlier-stage disease setting
more suitable than more conventional treatments such as chemotherapy.
Choudhury et al. note that “collectively the data indicate that vaccine therapy is
safe, and no significant autoimmune reactions are observed even on long-term
follow-up” (18). Such a safety profile would indicate the potential for a high
quality of life index, which is a unique feature when measured against the
adverse effects associated with traditional cancer treatments.
Despite a general consensus that cancer vaccines appear to be safe and
well tolerated, it is more difficult to draw conclusions regarding their efficacy.
To date, there have only been approximately 25 randomized phase 2 or 3 trials