Effect Observation Of Granulocyte Macrophage Colony-stimulating Factor Combined With Allogeneic Tumor Cellular Immunotherapy For Advanced Cancer

ObjectiveThe aim of this trial was to evaluate the feasibility,toxicity,immunologic,and clinical activity of GM-CSF secreting allogeneic cancer cell vaccine in advanced-stage patients.Methods and materialPatients:Patients were enrolled at our hospital,after institutional review board approval and written informed consent was obtainded,Including melanoma(n=11), ovarian cancer(n=10),breast cancer(n=10),renal cell carcinoma(n=15), gastric/colorectal carcinoma(n=14).All the patients were diagnosed stage IV,and stoped chemo- or radiotherapy at least one month.Patients were required to have a Karnofsky performance status of 60 to 80.Vaccine preparation:Cell line which have the same pathology with patients' tumor were used as the allogeneic tumor cells.Each injection contains inactivated tumor cell more than 1×10⁷ and GM-CSF-secreting cell which can secret GM-CSF more than lug/10⁶/24h.Vaccines administration: Vaccines were administered subcutaeous every week for a total six vaccinations.The vaccines were administered on the upper 1/3 inside of upper arms or thighs on a rotated.DTH were administered intradermal at lower 1/3 inside of forearms on the first and fifth vaccinations.Immune responses evaluation:1.Collected 10ml peripheral venous blood at pre- and protreatment,check the percentage of CD4+ T cell,CD8+ T cell,CD4+/CD25+/CD127-T cell,CD3-/CD16+56+/CD45+ cell by using flow cytometry,The levels of interferon-gamma,interleukin-4,transforming growth factor beta-1 were evaluated by using the ELISA.ResultsSafty:all the patients completed the treatments.Vaccines treatment were generally well tolerance.the most common vaccine-related adverse events were self-limited injection site reactions,erythema induration(94%),pruritus(60%),vesicular(4%) and pain or soreness at the injection site(94%).All the injection site reactions were grade I orâ…¡in severity.Seven patients reported fever,lower than 39℃.one patients had headache and dizziness,but got better without treatment.No clear evidences of vaccine-associated adverse events.Clinical responses:One patient dead.No patients achieved a partial or complete tumour responses.Four achieved mixed responses (MR),with regression of at least one tumour mass.40 patients maintained stable disease for at least 4 weeks following vaccine initiation.16 patients progressed, among them seven had liver metastasis,two had brain metastasis,and 1 had lung metastasis.To 30/6/2008 8 patients dead results in diseases progression,among them 6 had liver metastasis,one had brain metastasis.Median overall survival was 5.5 months,four patients were alive more than 1 years.Immune responses:Analysis of immune responses to vaccine was hampered by the polyvalent natural of the whole tumor cell used as the immunogen.Thus,immune responses to vaccination were assessed by measurement of vaccines injections site induration,and DTH reactions of intradermal injection of allogeneic tumour cell.DTH were positive in 44 of 50 patients,3 of 16 in progressed patients,34 of 40 in stable disease patients.DTH reactions were seen in stable disease patients more than in progressed patients(χ² =22.54,P <0.005).DTH responses level and injection site reaction level exist linear correlation(R²=0.594,P<0.001).Findings,patients immune system was activated at pro-treatment by test the changes of lymphcytes substype and related cytokines.TGF-β₁ significantly decreased in melanoma and renal cell carcinoma patients at pro-treatment(p<0.05). CD8+T cell significantly increased in melanoma,ovarian cancer,renal cell carcinoma patients at pro-treatment(P <0.05).Treg cell significantly decreased in all patients at pro-treatment.IFN-γonly observed increased tendency,no statistical significance at pro- and pre-treatment.Other cytokines and lymphocytes substypes no clear tendency. CD8+T cell significantly increased and Treg cell decreased in stable disease patients at pro-treatment(P <0.001,P <0.001).Treg cell was observed significantly decreased only in progressed patients(P <0.05).ConclusionsThis non-patient-specific cancer immunotherapy has a favorable safety profiles and is immunologically active.Continued clinical tial is warranted...