A clinical trial of active immunotherapy with anti-idiotypic vaccine in nasopharyngeal carcinoma patients

To investigate the effect of active immunotherapy with anti idiotypic vaccine i n patients with nasopharyngeal carcinoma (NPC) Methods Anti idiotypic antibodies (2H4/5D3) bearing the internal image of the NPC antig en were used in active immunotherapy in NPC patients receiving radiotherapy Antibodies and cytokine levels in patient sera were determined using ELISA befo re and after active immunotherapy IL 2 mRNA expression in the peripheral bloo d mononuclear cells (PBMC) was measured by in situ hybridization Results Nineteen patients with NPC at stage Ⅳ were treated with alum precipitated 2H4 or 5D3 Neither hypersensitivity nor adverse side effects were observed The l evels of anti anti idiotypic antibodies (Ab3) and anti NPC antibodies (Ab1’) were increased Human anti mouse antibodies (HAMA) were seen in 19 patients of the experimental group; the levels of Ab1’ did not increse in the control group Serum IL 2, IFN γ and TNF α levels were increased in most patients in th e experimental group, while no differences were observed in Ab1’ and cytokine le vels between pre and post therapy in the control group In addition, IL 2 m RNA expression in PBMCs from NPC patients was closely related to serum IL 2 ( r =+0 8829) levels by in situ hybridization Conclusions Anti idiotype vaccine is safe for clinical active immunotherapy Anti idiotyp ic vaccine might be able to enhance humoral and/or cellular immunity in NPC pati ents receiving radiotherapy

A clinical trial of active immunotherapy with anti-idiotypic vaccine in nasopharyngeal carcinoma patients

OBJECTIVE: To investigate the effect of active immunotherapy with anti-idiotypic vaccine in patients with nasopharyngeal carcinoma (NPC). METHODS: Anti-idiotypic antibodies (2H4/5D3) bearing the internal image of the NPC antigen were used in active immunotherapy in NPC patients receiving radiotherapy. Antibodies and cytokine levels in patient sera were determined using ELISA before and after active immunotherapy. IL-2 mRNA expression in the peripheral blood mononuclear cells (PBMC) was measured by in situ hybridization. RESULTS: Nineteen patients with NPC at stage IV were treated with alum-precipitated 2H4 or 5D3. Neither hypersensitivity nor adverse side effects were observed. The levels of anti-anti-idiotypic antibodies (Ab3) and anti-NPC antibodies (Ab1') were increased. Human anti-mouse antibodies (HAMA) were seen in 19 patients of the experimental group; the levels of Ab1' did not increase in the control group. Serum IL-2, IFN-gamma and TNF-alpha levels were increased in most patients in the experimental group, while no differences were observed in Ab1' and cytokine levels between pre- and post-therapy in the control group. In addition, IL-2 mRNA expression in PBMCs from NPC patients was closely related to serum IL-2 (r = + 0.8829) levels by in situ hybridization. CONCLUSIONS: Anti-idiotype vaccine is safe for clinical active immunotherapy. Anti-idiotypic vaccine might be able to enhance humoral and/or cellular immunity in NPC patients receiving radiotherapy.

New progress in active immunotherapy targeting to amyloid beta

Alzheimer's disease(AD) is one of the most common types of dementia whose hallmarks include neurofibrillary tangles and senile plaques. The latter are mainly composed of amyloid-β proteins(Aβ), and it's suggested that Aβ may be the causative factor in AD pathogenesis. Immunotherapy targeting Aβ for preventing aggregation of Aβ and mildly clearing amyloid plaques has been a hot topic since 1999. Although the first clinical trial of Aβ vaccine, AN-1792, failed in phase II, its results suggested some key points in the design of Aβ vaccines. Avoiding the possible toxic Aβ specific T cell response and inducing a Th2 type cellular immune response may be beneficial for Aβ immunotherapy. Many associations and research groups are working on Aβ vaccine and some progress has been made in recent years. In this review, we have provided a detailed summary of past Aβ vaccines, which have been sorted by the immunogen, and we also discuss some recent progress and future perspectives.

Vaccination with a Recombinant Chicken FGFR-1 Bypasses Immunological Tolerance against Self-FGFR-1 in Mice

The possibility that a recombinant protein vaccine based on xenogeneic homologous FGFR-1 of chicken induces production of autoantibodies against self-FGFR-1 in BALB/c mice was examined by using ELISA, Western blot analysis and ELISPOT assay respectively. Autoantibodies against mouse FGFR-1 were identified by Western blot analysis and ELISA. Compared with the two control groups, the number of APBCs, which were detected by ELISPOT assay, was significantly in- creased in the spleens of mice immunized with cFR1 （P〈0.05）. IgG1 and IgG2b, which were detected by ELISA, were the major subclasses and were substantially increased in response to chicken FGFR-1 when compared with control group. The recombinant chicken FGFR-1 protein used as a vaccine can induce autoantibodies against self-FGFR-1 in mice and provide a basis for the active immunotherapy of tumor angiogenesis.

ANTI-METASTATIC EFFECT OF ONCOLYSATES FROM MURINE MELANOMA CELLS TRANSFECTED WITH RECOMBINANT VACCINIA VIRUS ENCODING HUMAN IL-2

Oncolysates, debris of tumor cells, have been proven to be effective in active immunotherapy of cancer. In this experiment, the oncolysates from murine melanoma cells B16F10 transfected by recombinant vaccinia viruses encoding human IL2(IL2VBO) were used as vaccine. After treatment of tumor bearing mice with pulmonary metastases by intravenous injection of IL2VBO or rVVIL2, higher level IL2 activity was detected in the serum of IL2VBO or rVVIL2 treated mice at 8h. Further experiment results demonstrated that IL2VBO significantly reduced the number of pulmonary metastases and prolonged the survival time of tumorbearing mice when compared with other preparations. Fresh peripheral blood lymphocytes from IL2VBO treated mice showed potent cytotoxicity to B16F10 cells and YAC1 cells. But only cytotoxicity to B16F10 cells is more marked than that in rVVIL2 group, indicating that the IL2VBO could induce specific and non specific antitumor immunity. Because IL2 expression was at the same level in the serum of IL2VBO or rVVIL2 treated mice, the results suggested that the specific antitumor immunity induced by IL2VBO might contribute to the enhanced therapeutic effect of IL2VBO.

CELLULAR IMMUNITY EFFECT OF LEUKEMIA VACCINE ON TUMOR BURDEN RAT

Objective To evaluate the effect of the active specific immunotherapy with leukemia vaccine in the malignant hematopoietic diseases. Methods We established the animal models by inoculating C 57 BL/6 rats with FBL 3 erythroleukemia cells and prepared three types of tumor vaccine, which were administered on the rats respectively. The MTT colorimetric assay was adopted 2 and 4 weeks later to test the cytotoxicity of macrophage( M Φ ) and that of cytotoxic T lymphocyte(CTL) derived from the rats injected with tumor vaccines, and compared the results with the control group. Results With the growth of erythroleulemia cells in the rats, the cellular immunity was seriously depressed, and the inhibition of specific cellular immunity was later than that of non specific cellular immunity. The tumor vaccine made from inactivated tumor cells, IFA and cytokines (rGM CSF, rIL 2 and rIL 6), promote the cellular immunity of tumor burden rats, especially the specific cellular immunity more efficiently than that of tumor vaccine made from inactivated tumor cells and IFA, but the third vaccine made from inactivated tumor cells alone has no effect. Conclusion The tumor vaccine made from inactivated tumor cells with addition of IFA and cytokines (rGM CSF, rIL 2 and rIL 6) provides a promising future in the active specific immunotherapy against hematopoietic tumor.

A concise review of immunotherapy for glioblastoma

Glioblastoma(GB)is the most common and aggressive form of primary brain tumors in adults with a universally poor prognosis despite multimodal management including surgery,chemotherapy and radiation therapy.Among the novel therapeutic strategies,immunotherapy deserves particular attention with its potential to evoke biologic response and harness the host immune system.Considerable success achieved for other tumors has elicited great enthusiasm and prompted research on immunotherapy for GB.While the central nervous system has traditionally been thought of as an immune-privileged site,our understanding is being refined with emerging evidence.Several studies have been conducted and more are under way to establish the role of immunotherapy in management of GB.Immunotherapy of GB has yet resulted in mixed success with conflicting research findings,emphasizing the need for extensive study before its integration into routine clinical practice.Although there is a lot of room for improvement,immunotherapy for GB may be feasible and serve as a viable management strategy broadening and strengthening the therapeutic armamentarium to combat this deadly disease.Herein,we present a concise review of immunotherapy for GB.

上期临床病案讨论结果

上期临床病案讨论结果术前诊断左上腹巨大包块：①腹膜后包块（嗜铬细胞瘤？）；②左肝肿瘤？手术情况于１９９４年５月７日在静脉复合麻醉下取双侧肋缘下人字形切口行剖腹探查术。术中见肝脏正常，未扣及结节或肿块，但在左肝下缘与胃小弯之间发现一凸出的巨大肿块。切开...