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At least 19 recordsLinked to original sources
PubMed1984

[Tumor-specific immunotherapy: active immunotherapy by augmenting the induction of tumor-specific effector T cells through a T-T cell interaction mechanism].

Recent progress in tumor-specific immunotherapy was reviewed. Methods involved include a) utilization of tumor-specific monoclonal antibodies in conjugation with various anti-cancer agents, b) adoptive transfer of anti-tumor effector T cell clones elaborated in vitro in the presence of interleukin-2 and c) active tumor-specific immunotherapy by augmenting the generation of tumor specific effector T cells. This paper focused especially on the amplified induction of tumor-specific immunity by T-T cell interaction between helper T cells and anti-tumor effector T cells. Data were provided indicating successful tumor-specific immunotherapy in autochthonous as well as syngeneic tumor models and such results were discussed in the light of the future clinical application of the tumor-specific active immunotherapy.

Animals↗
PubMed2005

Clinical trials targeting lung cancer with active immunotherapy: the scope of vaccines.

Successful active immunotherapy is expected to be specific and nontoxic. Until now, the success of immunotherapy in cancer has been sporadic and unpredictable. This has been attributable in part to the lack of a full understanding of the mechanistic underpinnings of immune regulation. Furthermore, the lack of systematic success of immunotherapy, as argued in this review, stems from failing to effectively target tumors such as non-small cell lung cancer. In this review, the rationale and design for induction of immunity to non-small cell lung cancer and clinical trials of the most important lung cancer vaccines in development are discussed.

Antigens, Neoplasm↗
PubMed1975

[Active immunotherapy of acute leukemia and leukemic lymphosarcoma. Results of 10 years. Study of 200 cases].

The authors report a ten year study of active immunotherapy using BCG and irradiated allogeneic leukaemic cells in 200 patients. In acute lymphatic leukaemia, 57 out of 168 patients treated in this way remained in primary remission for 18 months to 10 years after active immunotherapy was begun, the relapse rate became low after 18 months and nil after 36 months. The results varied according to prognostic factors: the cytological type, active immunotherapy being above all effective in small cell (microlymphoblastic and prolymphocytic) types with a hope of cure in 50 to 60 p.cent of cases; malignant cellular volume; meningeal deposits. In microlymphoblastic forms the possibility of survival at the 5th year is greater than 90 p.cent. After relapse during active immunotherapy sensitivity to chemotherapy does not seem to be diminished. Trials of active immunotherapy in acute myeloid leukaemia are worthy of further pursuit. The results of active immunotherapy in leukaemic lymphosarcoma show that immunotherapy may be effective in preventing local recurrence, both of tumour as well as in the marrow. Four patients are in apparently complete remission for more than four years. On the basis of these results, trials of active immunotherapy for "residual disease" should be undertaken in the field of cancerology, going beyond the realm of leukaemias.

Adjuvants, Immunologic↗
PubMed2002

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.

Adult↗
PubMed1991

[Active immunotherapy of habitual abortion: is the danger greater than the therapeutic gain?].

Active immunotherapy is widely employed in the treatment of patients with habitual abortion, but it is comparable to the transfusion of blood or blood components with respect to possible complications such as undesirable immune responses and the possibility of transmitting infectious diseases. In fact, immunization with lymphocytes carries a greater risk of infection with cytomegalovirus than does transfusion of erythrocytes or platelets, a fact of particular relevance, since it represents a potential risk to the child. In addition, irregular antibodies to erythrocytes or platelets may be induced, which may have a harmful effect on both the mother and the child. The subsequent formation of autoantibodies and antibodies against cardiolipin in patients subjected to active immunotherapy has only recently been described. The significance of these and other possible immune responses is by no means clear, so that further investigation of the immunological side effects is urgently required. Active immunotherapy for habitual abortion demands strict medical indication, since the mechanism by which it protects the pregnancy has not been elucidated, and controlled studies have yielded differing results concerning therapeutic success. These factors must be taken into account when affected couples are counselled. The possible complications should be carefully weighed against the anticipated effects, since no vital indication exists in the case of habitual abortion, unlike most situations where the transfusion of blood products is contemplated.

Abortion, Habitual↗
PubMed2001

[Study on changes of serum T helper cell type 1 and 2 cytokines after active immunotherapy in women with unexplained habitual abortion].

OBJECTIVE: To investigate the changes of serum T helper cell (TH)1/TH2 type cytokines after the active immunotherapy in unexplained habitual abortion (UHA) women. METHODS: Concentrations of interleukin (IL)-2, IL-12, interferon (IFN)-gamma, IL-4, IL-10 and transforming growth factor (TGF)-beta 1 were measured by enzyme-linked immunosorbant assay (ELISA) method in sera from thirty-three cases of unexplained habitual abortion (UHA) women before and after active immunotherapy. Thirty normal non-pregnancy (NNP) women and thirty normal pregnancy (NP) women were taken as control. RESULTS: (1) Serum concentrations of IL-2 and IL-12 were higher significantly (P < 0.01) in UHA women [(13.3 +/- 13.8) ng/L and (50.5 +/- 25.8) ng/L, respectively] than those in NNP women [(4.6 +/- 6.4) ng/L and (20.3 +/- 28.2) ng/L, respectively]. Serum concentrations of IL-4 and IL-10 were lower significantly (P < 0.01) in UHA women [(13.8 +/- 1.0) ng/L and (13.5 +/- 0.7) ng/L, respectively] than those in NNP women [(14.5 +/- 1.2) ng/L and (14.9 +/- 2.4) ng/L, respectively]. However, there were no significant differences in serum concentrations of IFN-gamma and TGF-beta 1 between UHA women and NNP women. (2) Serum concentrations of IL-2 were lower significantly (P < 0.05) in NP women [(1.6 +/- 4.3) ng/L] than those in NNP women. Serum concentrations of IL-4 were higher significantly (P < 0.01) in NP women [(16.3 +/- 0.8) ng/L] than those in NNP women. But there were no significant differences in serum concentrations of IFN-gamma, IL-10 and TGF-beta 1 between NP and NNP women. (3) After active immunotherapy, serum concentrations of IL-2 and IL-12 were decreased significantly [(5.6 +/- 9.0) ng/L and (28.5 +/- 40.3) ng/L respectively, P < 0.01] whereas serum concentrations of IL-4 and IL-10 were increased significantly [(14.7 +/- 1.2) ng/L and (15.0 +/- 1.8) ng/L respectively, P < 0.01] in UHA women. In addition, no significant changes in serum concentrations of IFN-gamma and TGF-beta 1 were found in UHA women after immunotherapy. (4) As compared to NNP women. there were no significant differences in serum concentrations of the above-mentioned cytokines in UHA women after active immunotherapy. CONCLUSIONS: The results suggest that profile of TH1/TH2 type cytokines tilts to TH2 immunity in normal pregnancy, but to TH1 immunity in UHA. The active immunotherapy could make a shift from TH1 to TH2 immunity, thus favoring the maintenance of pregnancy.

Abortion, Habitual↗
PubMed2005

Active immunotherapy for advanced intracranial murine tumors by using dendritic cell-tumor cell fusion vaccines.

OBJECT: Immunotherapy for malignant brain tumors by active immunization or adoptive transfer of tumor antigen-specific T lymphocytes has the potential to make up for some of the limitations of current clinical therapy. In this study, the authors tested whether active immunotherapy is curative in mice bearing advanced, rapidly progressive intracranial tumors. METHODS: Tumor vaccines were created through electrofusion of dendritic cells (DCs) and irradiated tumor cells to form multinucleated heterokaryons that retained the potent antigen processing and costimulatory function of DCs as well as the entire complement of tumor antigens. Murine hosts bearing intracranial GL261 glioma or MCA 205 fibrosarcoma were treated with a combination of local cranial radiotherapy, intrasplenic vaccination with DC/tumor fusion cells, and anti-OX40R (CD134) monoclonal antibody (mAb) 7 days after tumor inoculation. Whereas control mice had a median survival of approximately 20 days, the treated mice underwent complete tumor regression that was immunologically specific. Seven days after vaccination treated mice demonstrated robust infiltration of CD4+ and CD8+ T cells, which was exclusively confined to the tumor without apparent neurological toxicity. Cured mice survived longer than 120 days with no evidence of tumor recurrence and resisted intracranial tumor challenge. CONCLUSIONS: These data indicate a strategy to achieve an antitumor response against tumors in the central nervous system that is highly focused from both immunological and anatomical perspectives.

Animals↗
PubMed1972

Histological evidence of tumour rejection after active immunotherapy in human malignant disease.

Active immunotherapy with multiple doses of tumour homogenate incorporated in complete Freund adjuvant was used to treat 12 patients with advanced malignant disease. Evidence of some tumour destruction was observed in 10. Improvement in general clinical condition and the disappearance of symptoms referable to tumour occurred in seven of the patients. The duration of improvement varied considerably. Histological evidence of lymphocytic infiltration, necrosis, and fibrous replacement of tumour tissue is presented.

Adult↗
PubMed2003

[Influences of active immunotherapy on T helper cell type 1 and 2 cytokines in women with unexplained habitual abortion].

OBJECTIVE: To investigate the influences of active immunotherapy on T helper cell (Th)1/Th2 type cytokines in women with unexplained habitual abortion (UHA). METHODS: A total of 55 patients with UHA were studied, including 30 cases after active immunotherapy (AIT) and 25 cases without any therapy (NAIT). Fifteen cases of normal nonpregnant (NNP) women were selected as control group. Supernatants from trophoblast-activated peripheral blood mononuclear cells (PBMC) of the three groups were tested by enzyme-linked immunosorbent assay (ELISA) for interferon gamma (IFN-gamma), interleukin-2 (IL-2), IL-4, IL-10. RESULTS: (1) The levels of IL-2 and IFN-gamma in AIT group [(108 +/- 37) ng/L and (110 +/- 52) ng/L, respectively] were lower significantly than those in NAIT group [(223 +/- 85) ng/L and (326 +/- 92) ng/L, respectively] (P < 0.05). The levels of IL-4 and IL-10 in AIT group [(50 +/- 11) ng/L and (140 +/- 37) ng/L, respectively] were higher than those in NAIT group [(23 +/- 11) ng/L and (52 +/- 28) ng/L] +/- (P < 0.05). The levels of IL-2 and IFN-gamma in NAIT group were higher than those in NNP group [(92 +/- 32) ng/L and (102 +/- 35) ng/L] (P < 0.05). The levels of IL-4 and IL-10 in NAIT group were lower than those in NNP group [(62 +/- 21) ng/L and (150 +/- 42) ng/L] (P < 0.05). The level of every cytokine had no difference in AIT group and NNP group (P > 0.05). (2) Twenty-six women in AIT group got pregnant, but 8 women experienced pregnancy loss repeatedly whose IL-2, IFN-gamma levels were higher than those in other 18 women got successful pregnancy and IL-4, IL-10 levels lower than the latter. CONCLUSIONS: UHA patients have Th1 type immunity to trophoblast and produce high-level Th1 type cytokines which probably result in pregnancy loss. Active immunotherapy could make a shift from Th1 to Th2 immunity, thus favoring the maintenance of pregnancy.

Abortion, Habitual↗
PubMed1998

Active immunotherapy with allogeneic tumor cell vaccines: present status.

This review will concentrate on allogeneic vaccines for melanoma The important principles of melanoma vaccine effectiveness are discussed in detail, followed by a review of the progress of several clinical trials investigating allogeneic vaccines. No therapeutic cancer vaccine has yet been approved for general use by the US Food and Drug Administration. However, much progress has been made in the field of vaccine immunotherapy, especially for the treatment of melanoma. Active immunotherapy with tumor vaccines is progressing rapidly as an emerging option for cancer therapy.

Antigens, Neoplasm↗
PubMed1979

Non-specific and specific active immunotherapy in a B16 murine melanoma system.

Conflicts amongst reports concerning the efficacy of both nonspecific and specific attempts at immunotherapy may be ascribed to different animal models utilizing tumors of different immunogenicity. We have selected the B16 mouse melanoma model as the example of a spontaneously occurring neoplasm that is histocompatible with the host and does have tumor-associated antigens. Attempts to alter tumor growth or survival with nonspecific active immunotherapy as well as with specific active immunotherapy were not successful. Nonspecific active pre-immunization failed to alter tumor take or growth. Specific active immunotherapy both with and without adjuvant did decrease tumor take and prolong host survival. The effects were increasingly documented at lower tumor cell inoculums and became less apparent with increase in the tumor cell challenge.

Adjuvants, Immunologic↗
PubMed1991

The improved effects of specific active immunotherapy on a rat fibrosarcoma by antitumor drugs.

We have tried to find out if the combination of a xenogenized tumor cell vaccine and antitumor drugs is able to induce a synergistic increase in the antitumor therapeutic effect. The degree of increase in the LTD50 (50% lethal tumor dose) is expressed numerically, as a quantitative index designed to compare degrees of transplantation resistance to tumor cell challenge. A LTD50 was achieved by an intradermal (i.d.) immunization with xenogenized tumor cells when challenged with tumor cells implanted intraperitoneally 2 weeks after the immunization: this LTD50 value was 527,000 times higher than that of the non-immunized group. When we combined this type of immunization with appropriate doses of bleomycin (BLM) or cyclophosphamide (CY), which are able to augment antitumor immunity, the LTD50 was 723,000-1,190,000 times higher than that of the non-immunized group. This increase in the LTD50 is definitely higher than that achieved by a single immunization with irradiated tumor cells (x 33,000) and combined with either BLM (x 93,000) or CY (x 140,000). We also studied the therapeutic effect of a tumor cell vaccine combined with antitumor drugs BLM or CY in tumor-bearing rats. We observed a synergistic effect caused by BLM or CY after i.d. immunization with xenogenized tumor cells: this showed a significant increase when compared with the therapeutic effects obtained by chemotherapy alone (P less than 0.01). Nevertheless, there was no evidence that the above antitumor effects is superior to the effect achieved by irradiated tumor cells.

Animals↗
PubMed2003

Translational development of active immunotherapy for hematologic malignancies.

Idiotype (Id) antigen is a unique, truly tumor-specific antigen. Early preclinical studies have shown Id vaccination to be efficacious against established tumors, and this effect is enhanced by addition of the cytokine granulocyte-macrophage. One clinical study showed that injections of immunoglobulin derived from each patient's tumor cells (immunoglobulin-Id protein) induced Id-specific immunologic responses of the humoral type and/or the cell-mediated type, and that those patients who experienced cell-mediated responses achieved molecular remissions. Addition of cytokines to Id vaccination can greatly influence the magnitude and phenotype of the immune response to protein antigens. One cytokine, granulocyte-macrophage colony-stimulating factor, is particularly important to the success of cancer immunotherapy. Some studies have shown the ability of granulocyte-macrophage colony-stimulating factor to enhance protective tumor immunity and help prolong survival rates. A number of trials have been conducted on the use of Id vaccination in the treatment of follicular lymphoma. Currently, the National Cancer Institute (Frederick, MD) is conducting a large, randomized, multicenter, phase III trial comparing chemotherapy alone versus chemotherapy followed by vaccination with Id-keyhole limpet hemocyanin plus granulocyte-macrophage colony-stimulating factor. This pivotal study is the final step before vaccine therapy might be considered as an option of standard care for patients with follicular lymphoma.

Adjuvants, Immunologic↗
PubMed1997

A review of the design of vaccine efficacy trials and a proposal for the design of the VA Cooperative Study of Active Immunotherapy of HIV Infection.

We review the design of vaccine trials based on a search of the medical literature over the past four years, and present the proposed design of a therapeutic HIV vaccine efficacy study by the Department of Veterans Affairs Cooperative Studies Program. We explore the reasons for the atypical design of many vaccine trials, particularly the analysis of efficacy and how it differs from the more usual intent-to-treat analysis used in nonvaccine trials.

AIDS-Related Opportunistic Infections↗
PubMed2003

Tumors as elusive targets of T-cell-based active immunotherapy.

The understanding of tumor-host interactions remains elusive despite significant progress in the identification of tumor antigens (TAs) recognized by autologous T cells. In particular, most human tumors do not regress and continue to grow in spite of spontaneous or immunization-induced immune responses demonstrated in circulating lymphocytes. Indeed, systemic immune responses might insufficiently address the complexity of tumor-host interactions because of factors, such as (1) the lack of productive T-cell receptor (TCR) engagement with epitope owing to qualitative and/or quantitative defects in the generation and maintenance of the immune response, (2) insufficient costimulation provided by the host, (3) the lack of localization of the immune response in target tissues and (4) the complexity of tumor-host interactions within the tumor microenvironment caused by temporal changes in tumor phenotypes and an array of immune mediators expressed in the tumor microenvironment. Here, we will review current knowledge of the different 'levels' of immune response that might be necessary for immunotherapy to be effective in the treatment of cancer. Furthermore, we will discuss the information still required in order to understand the mechanism(s) governing tumor rejection by the immune system in response to TA-specific immunization.

Animals↗
PubMed1995

[Idiopathic habitual abortion: experiences with active immunotherapy].

The effect of lymphocyte transfusions on the stabilisation and successful outcome of pregnancy was investigated in 30 women with recurrent abortions presumably caused by immunologic factors. Lymphocyte concentrates were obtained from stored whole blood of the husbands and transferred by intravenous injection. Exclusion criteria for this study were the presence of antipaternal lymphocytotoxic antibodies in the patient's serum (cross match) or an advanced pregnancy (> 12 weeks). After transfusion of paternal lymphocytes 19 (63%) women had uncomplicated and successful pregnancies whereas 11 (37%) suffered again from early pregnancy loss. Two out of these 11 patients aborted twice. The probability of a successful treatment decreased as soon as lymphocytotoxic antibodies appeared in the patient's serum (p < or = 0.021). Women with a lower number of abortions before treatment carried their pregnancies to full term more frequently (p < or = 0.03). The number of transfusions, the period between start of treatment and conception as well as the distribution of age within the two groups had no significant effect on the outcome of therapy. A lack of lymphocytotoxic antibodies or their late appearance during treatment give a positive prognosis for the progress of pregnancy. Compared with a fertile control group, couples with habitual abortions showed no significantly increased HLA sharing. Immunisation with paternal lymphocytes in cases of presumably habitual abortions due to immunologic factors appears as an effective therapy with only few side effects. Large, randomised, double-blind, and placebo-controlled trials are needed before drawing conclusions.

Abortion, Habitual↗
PubMed1996

Passive and active immunotherapy for experimental pneumococcal pneumonia by polyvalent human immunoglobulin or F(ab')2 fragments administered intranasally.

Experimental pneumococcal pneumonia in leukopenic BALB/c mice enabled evaluation of passive immunotherapy with human polyvalent intravenous immune globulin (IVIG) given intravenously or intranasally and with F(ab')2 fragments administered intranasally. For intravenous and intranasal IVIG, the respective effective doses were < 5 but > 0.5 mg/kg and < 250 but > 2.5 micrograms/kg. For F(ab')2 fragments, the effective dose was < 500 but > 2.5 micrograms/kg. Assessment of the acquired immune responses of passively protected mice and convalescing controls 3 weeks after primary infection showed that antibody responses to whole bacteria were serotype-specific in all mice. Mice protected with IVIG and F(ab')2 fragments had more antibodies to pneumolysin than did controls. In addition, treated mice acquired greater resistance to reinfection than untreated survivors. Thus, local passive immunotherapy may be an effective means of treating pneumococcal pneumonia and may promote acquired resistance to reinfection.

Administration, Intranasal↗