Page 100 - Bio Engineering Approaches to Cancer Diagnosis and Treatment

98 CHAPTER 4 Immunotherapy

Until 2003, more than 1000 DC vaccines were introduced and half of them
shown minimal side effect [85]. These data reveal the safety of DCs usage for cancer
vaccination.

4.6.1.2 Peptide/protein vaccine
The TAAs are recognized by T cells when they bind to MHC molecules. Then, acti-
vation of host immune system cause cancer tissue to be destroyed. Hence, cancer
vaccines in this strategy are produced by TAAs peptides. Peptide vaccines have
low toxicity profile, the production of these vaccines is somehow easy, and they are
specific to their target and are not costly in comparison with other methods. Early
peptide vaccines are prepared by single peptides causing problems, for example, at
different stages of cancer, different peptides are expressed which is resulted in single
peptides vaccines inefficiency [76,86].
The novel strategies in peptide vaccination have concentrated on targeting mul-
tiple peptide epitopes.
In order to distinguish the immunogenicity of multiple peptide vaccines, some
clinical trials have been done and have shown promising result on patients with
melanoma and glioblastoma [87,88]. The advantages of multiple epitopes have
increased the probability of multiple T-cell activation and conquering the problem
of loss or change of tumor epitopes (tumor peptides may change in different stage of
cancers or can be different case by case) therefore, multiple peptide vaccinations can
sufficiently keep T cell response [76]
More recently, scientists have found that some natural epitopes are not immuno-
genic. Therefore, some modifications are indeed vital to enhance their immunogenic-
ity. Modified peptides are more capable to enhance the T cell immunogenity [73].
There are two different approaches in peptide vaccine production:

a. Self-antigens
Most of the peptide based cancer vaccines are produced with nonmutated self-
antigens. These TAAs are expressed in both normal and cancerous cells, but some-
times these antigens overexpress in tumor cells. For example, cancer testis antigens
(CTAs) express in normal and tumor cells, however, in normal tissues they express
only in germline cells. From aforementioned data it is understood that using of self-
antigens as a peptide vaccine causing central tolerance and prevent sufficient immune
response against tumor cells, on the other hand however, powerful immune responses
lead to autoimmune problems [76].
b. Neoantigens
In order to define neoantigens, these peptides are mutation-based antigens merely
existed in cancerous cells with lower risk of autoimmune side effects or central toler-
ance. These antigens named TSAs and are generated from mutations (point muta-
tions, translocations, insertions or deletions), viral proteins and posttranslational
modifications (PTM) [76,89].