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102    CHAPTER 4  Immunotherapy




                         worked on modification strategies to stabilize and enhance the loading rate of both
                         Liposomes and PLGA [70].

                         •  Cancer vaccines on basis of scaffolds
                            The reason why scientists are motivated to use scaffolds is due to the benefits of
                         local delivery systems. Local delivery may decrease the systemic toxicity and boost
                         the immune effect with lower doses [97].
                            Scaffold delivery systems mainly have made of polymers and hydrogels. These
                         systems are typically large, so they remain in the injection site. Moreover, scaffold
                         base delivery systems are capable in encapsulation of different molecules.
                            There are three efficient materials that have been used as cancer vaccines scaffolds,
                         including PLGA, hydrogels which mainly contains of alginate and mesoporous silica
                         micro-rods (MSRs), these scaffolds are all biodegradable and biocompatible [70].
                            The scaffolds play a key role in mimicking the natural lymph node function,
                         so they are vital for immune cells to interact and expand. Based on these points,
                         some factors in scaffold fabrication seems demanding, like: porosity and intercon-
                         nection between porous which are essential for cell nutrition and cell encapsulation
                         respectively, hence scaffolds must meet some factors, including: rigidity to bear
                         the forces, porosity to provide convenient penetration, and control the signaling
                         maters [97].
                            In conclusion, combination of biomaterials with cancer vaccines has shown
                         promising results by reducing the dosage, increasing the safety due to their local-
                         ized administration, boosting the efficiency resulted from their targeting ability
                         and also biomaterials can influence on signaling. However, some obstacles exist
                         in their usage: First, there are far differences between academic researches and
                         clinical trials, animals may be treated in a different way from humans when they
                         faced to biomaterials. Second, most of the investigations on biomaterials for can-
                         cer vaccination approaches have been done on melanoma which is different from
                         solid and hematological tumors, so implantation seems to be different from cancer
                         to cancer. Finally, some troubles in commercial and clinical purposes have been
                         happened, including: the large scale production, and FDA approval. In order to
                         facilitate the clinical trial phases it is better to use FDA approved biomaterials like
                         PLGA [70,71].
                            It is worth noting that, on one side, designing suitable preclinical platforms for
                         cancer vaccines is difficult due to the differences in human and mouse immune sys-
                         tems. On the other hand, mouse tumors may not always mimic human cancers in
                         reality [89].


                         4.6.6  Case study
                         Maslak et al. have succeeded to produce a vaccine named galinpepimut-S against
                         WT1 protein as a treatment for those who suffer from AML. In phase II study
                         patients were administered vaccines for at least six doses in 10 weeks. The results
                         have revealed that the vaccine is well tolerated and 22 patients were well treated [98].
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