Our study was done with two aliquots of 5 × 107 cells for each
dose. This dose is similar to that of other studies that used doses ranging between 8.2 and 10 × 107 cells[11–13]. Another trial demonstrated that a dose of 1.2 × 107 cells selleck products did not reach a truly maximum tolerated dose. Given that there is no clear consensus about whether or not the route of immunotherapy influences on the efficacy of the vaccine, we chose to apply it by a subcutaneous and intradermal route. In addition to the high level dose, the vaccine was well-tolerated as noted in many studies[11–15], even in a study in Hepatitis C Virus (HCV) infected individuals. We observed no local reaction, but one patient presented fatigue, chills, pancytopenia and hyponatremia five days after the first dose of the vaccine. Usually, the reactions after immunotherapy occur within 24-48 hours after the infusion[12, 17]. Therefore, we hypothesize that the patient developed an infection, but it cannot be proved because the bacterial cultures and viral tests were negatives. Three patients had a longer time survival than expect for their TNM stage. Two of these (patients A-1155463 price #4 and #5) had a survival almost twice greater than the expected average and they were the only ones that expressed HER-2 and
CEA together. Although the small sample size precludes the meaningful assessment of the therapeutic effects and any results may be due to chance, we cannot Vorinostat mouse exclude that these clinical outcomes may indicate some therapeutic efficacy. Many variables related to the host and the see more vaccine may be important to reach therapeutic efficacy. The immunologic resistance of a tumor to immune effector cells at the local level remains a potential limitation to the vaccine efficacy, and the choice of antigens is also relevant
to the therapeutic efficacy and potentially to the immunologic responses to vaccines. Furthermore, the characteristics of the tumor antigen may change and it can become unresponsive to the initial tumor-antigen targeted therapy as tumors grow during conventional therapy[14, 15]. We decided to produce a multivalent vaccine according to each patient tumor’s antigen expression, observed by immunohistochemistry, to avoid this phenomenon and improve the results of immunotherapy by inducing a broad repertoire of antigen-specific T cells. Indeed, the profile of antigens with better therapeutic responses has not yet been determined. The patterns of reactivity ranged between individuals (Figure 2). Two patients expressed a significant immunologic reaction after the first dose; another two presented a boosted response after the second dose and one showed a mixed response. The lymphoproliferation assay showed an improvement in the specific immune response after the immunization (Figure 3). However, this response was not long lasting and a tendency to reduction 2 weeks after the second dose of the vaccine was observed.