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4.6 Cancer vaccine     99




                     Neoantigens are defined into two groups: shared neoantigens and personalized
                  neoantigens. Shared neoantigens are those which are common in patients with the
                  same tumor type and not expressed in normal tissues. These antigens have the benefit
                  of general vaccination for people suffering from similar cancers. However, neoanti-
                  gens may be variable from cancer to cancer or in a similar cancer neoantigens are dif-
                  ferent in each patient. So, personalized vaccines seem to be the best vaccines which
                  could give sufficient immune responses [76].
                     Personalized peptide vaccines are developed in order to solve the problem of
                  peptide vaccines disability in triggering the immune system against cancer cells. In
                  this method by consideration of the preimmunity status of patient, personalized can-
                  cer vaccine has been invented [73]. Some scientists believe that although this novel
                  approach may boost the effect, such expensive methods with the low rate of publicity
                  would cause further limitations.


                  4.6.2  DNA/mRNA vaccines

                  •  DNA vaccines
                     The usage of DNA as a vaccine is illustrated in early 1990, plasmid DNA
                  can promote immune system reaction against tumor antigens [90]. Plasmid DNA
                  includes unmethylated and repeating cytosine-guanine area therefore, these DNA
                  have the ability to trigger immunogenicity, so they play a role as both adjuvant and
                  antigen [70,91]. There exist some problems with the usage of bare DNA, for exam-
                  ple, miss-targeting and inefficient uptakes by the cells have happened in the previ-
                  ous researches. These troubles provide scientists with new efficient methods which
                  cause the APCs to recognize plasmid DNA in a better way. Electroporation (EP) is a
                  method by which the membrane of the cells become permeable with the help of elec-
                  tronic pulses, it has been revealed that this process extends the antigen uptake a lot.
                  There seems to be one another fruitful way to boost the impact of the DNA vaccines.
                  In this strategy the DNA is coated with metals (especially heavy metals like: gold),
                  then cannonaded to the antibody presenting cells so, it will decrease the required
                  dose adequately. Despite the aforementioned strives, only a few progression have
                  been seen in DNA vaccination resulted from their low rate of immunogenicity [70].
                     It is worth nothing that, DNA vaccines seems to be efficient due to their simplic-
                  ity, easy production and safety. Hence, there is ongoing researches on DNA vaccina-
                  tion especially in prostate cancer [92].

                  •  mRNA vaccines
                     mRNA vaccines seem to be a good substitute for DNA vaccines because they
                  are safer. In this approach, messenger RNA are used for immune alertness but it has
                  been shown that mRNA vaccines are not stable leading to low development in these
                  vaccines. More recently, with the help of stabilize improvement, mRNA vaccines
                  get more attractive. These vaccines in combination with liposomes and protamines
                  provide better immune reaction [73].
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