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4.4 Chemo immunotherapy        83




                     The other subgroup is related to the use of some methods to increase T cell
                  responses. For instance, increasing tumor antigen presentation can increase the
                  T cell response. One of the preclinical studies of this subject can be found in
                  the study of Dewan et al. which was conducted in animal model of mice. They
                  have injected TSA mouse breast carcinoma cells into mice and after the tumor
                  was created, they have used an agonist of Toll-like receptor-7 (TLR-7), in com-
                  bination with three fraction of 8 Gy of RT, and also they have used low-dose
                  cyclophosphamide before start of treatment with imiquimod and RT. Their results
                  have shown that with respect to the effect of TLR on the activation of DC and
                  further increase of T cell response, this therapeutic approach has prevented tumor
                  growth. And it is important to note that cyclophosphamide has increased the ther-
                  apeutic effect [35].
                     The two following methods, vaccine therapy plus RT and the use of monoclonal
                  antibodies in combination with RT, are important methods that have been considered
                  in recent years. By introducing tumor antigens, the vaccine therapy stimulates the
                  immune system against tumor antigens. In a study in 2016, an animal model of mice
                  with melanoma was used to evaluate the efficacy of RT in combination with vaccine
                  therapy. Combination treatment with focal RT and LM-based vaccine has been per-
                  formed. They have used 16 Gy small-animal radiation research platform (SARRP)
                  7 days after tumor implantation. Then the results of this combined treatment with the
                  result of using RT alone as a treatment or vaccine alone as treatment, have indicated
                  that the use of RT as a treatment, minimal inflammation was seen in the treated
                  tumor. In contrast, by using of LM-vaccination as a treatment, inflammation was
                  increased. And the results of a treatment with combined method have shown pres-
                  ence of an intratumoral lymphocyte infiltrate and the results have indicated that the
                  use of a combined method has led to an increase in the survival of this animal model
                  with melanoma [36].
                     The use of antibodies to target antigens in addition to topical radiotherapy as
                  well as the use of antibodies with other therapeutic methods, such as targeting a spe-
                  cific cytokine, for instance, TGFβ, to control a cancer treatment has been extremely
                  attractive for researchers in the last decades. In this regard, Rodríguez-Ruiz et al.
                  in 2019 has reported the use of monoclonal antibodies with radiotherapy has been
                  shown to be effective in treating subcutaneous tumors of either 4T1 breast cancer
                  cells or MC38 colorectal tumors induced in an animal model of mouse. By knowing
                  that blocking TGFβ leads to an increase in abscopal effect, they have used anti-PD-1
                  and anti-CD137 monoclonal antibodies plus a TGFβ monoclonal antibody (1D11)
                  with a regimen local radiotherapy and have managed to find out that the use of this
                  method has increased the effect of abscopal [37].



                  4.4  Chemo immunotherapy

                  As the success rate of antibodies from the earliest humanized forms have not been
                  less than 15%.
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