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At least 73 records · Page 4Linked to original sources
PubMed1989

Immunotherapy using the streptococcal preparation OK-432 for the treatment of uterine cervical cancer. Cervical Cancer Immunotherapy Study Group.

The efficacy of immunotherapy using a streptococcal preparation, OK-432, was evaluated in each clinical stage of uterine cervical cancer. The 382 eligible patients were stratified by clinical stage and presence/absence of surgery. Within each stratum, patient's were randomly allocated to OK-432 treatment or to control treatment. OK-432 significantly inhibited recurrence in patients with stage II cervical cancer; the recurrence-free interval and survival time were remarkably prolonged in patients with stage II disease who underwent surgery. However, OK-432 did not significantly prolong these parameters in patients with stage III disease. Retrospective analyses revealed that in patients with or without lymph node metastases who underwent surgery, the recurrence-free interval and survival time were significantly prolonged by OK-432 treatment. These results indicate that OK-432 is an effective and useful postoperative immunotherapeutic agent for uterine cervical cancer.

Biological Products↗
PubMed1989

Hymenoptera venom immunotherapy. II. T proliferative and T suppressive activities induced by Vespula immunotherapy: effects on long-term antibody responses.

Thirty-five children who had exhibited major clinical reactions to yellow jacket stings were desensitized during an 8-day rush immunotherapy (RIT). Maintenance treatment was continued for at least 1 year in all cases and for 2 years in 21 cases. Blood samples, obtained before, during, and after RIT, were analyzed for specific T proliferative (TP) and T suppressive (TS) cell activities and for specific IgE, IgG1, and IgG4 levels. TS and TP cell activities increased during RIT (p less than 0.001) and remained elevated throughout the 2-year follow-up. There were transient rises in specific IgG1 and IgE during RIT, but the levels of both decreased thereafter. Specific IgG4 increased throughout the follow-up period. The data indicate that the levels of specific IgE and specific IgG1 were correlated with TP cell responses (inducers) and TS cells responses (suppressors) and therefore might be controlled by them; data also suggest that TS cell responses should play a role in the IgG4 response. These changes in TS and TP cell responses and antibody responses have been incorporated into a model of antibody-response regulation by cell-mediated immunity in this type of allergy.

Adolescent↗
PubMed1999

Allogeneic cell-mediated immunotherapy for eradication of minimal residual disease: comparison of T-cell and IL-2 activated killer (LAK) cell-mediated adoptive immunotherapy in murine models.

In the course of allogeneic bone marrow transplantation (BMT), avoiding graft-versus-host disease (GVHD) while retaining the antileukemic effects of the T cells remains a major challenge. T-cell depletion (TCD) reduces the incidence of GVHD but increases the relapse rate after allogeneic BMT. We attempted to develop a regimen that would retain or increase the graft-versus-leukemia effect induced by donor T cells while preventing GVHD. Immunosuppressed mice were given immunocompetent donor cells, i.e., fresh lymphocytes or lymphokine-activated killer (LAK) cells differing from the host in major (MHC) or minor (MiHC) histocompatibility antigens. Engraftment of donor cells was documented by polymerase chain reaction analysis. Administration of MHC- and MiHC-incompatible allogeneic LAK cells, especially in conjunction with recombinant interleukin-2 (rIL-2), increased disease manifestations and mortality associated with GVHD. On the other hand, irradiated LAK cells or TCD-LAK cells prevented GVHD in both mice models studied. Phenotypic analysis of LAK cells demonstrated that CD8(+)-equivalent (Lyt-2) T cells are of significance in aggravation of GVHD. The in vitro cytotoxic capacity of LAK cells against MHC-nonrestricted target cells was not reduced by either irradiation or TCD. These results provide the background for designing improved protocols for immunotherapy of residual disease after BMT. In addition, the data imply that antitumor effects may be retained by irradiated rIL-2-activated allogeneic cells without causing GVHD. Whereas unmodified allogeneic LAK cells can induce more effective graft-versus-leukemia effects at the cost of GVHD, irradiated allogeneic donor LAK cells might play some role in eradication of minimal residual disease following autologous or allogeneic BMT without causing GVHD.

Animals↗
PubMed1986

Sub-class of IgG anti-bee venom antibody produced during bee venom immunotherapy and its relationship to long-term protection from bee stings and following termination of venom immunotherapy.

The IgG sub-class antibody response to bee venom in the four sub-classes was investigated in ten patients during and after venom immunotherapy. All patients tolerated a bee sting challenge 1, 2 and 3 years after the start of treatment as well as 1 and 2 years after treatment was stopped. Anti-phospholipase A2 (PLA2) antibodies were of IgG1 and IgG4 sub-class and rose early in treatment, IgG1 anti-PLA2 fell to pre-treatment levels after 3 years in contrast to IgG4 anti-PLA2 levels, which remained high during maintenance therapy and declined relatively little in the 2 years after the termination of treatment. This data shows that IgG4 antibodies are maintained in the absence of monthly maintenance injections and suggests that they may provide long lasting clinical protection from insect stings.

Adolescent↗
PubMed1986

[Lymphocyte subpopulations in sensitization and specific immunotherapy in an experiment. Lymphocyte subpopulations in the specific immunotherapy of microbial allergy and subsequent heterologous pollen sensitization].

The influence exerted by the specific immunotherapy (SIT) of delayed hypersensitivity (DH) to staphylococci and subsequent sensitization with tarragon pollen on the level of immunocompetent cells in the blood and lymphoid organs of guinea pigs was studied. On the whole, SIT normalized the characteristics of T- and B-lymphocytes, altered as the result of experimentally induced DH: the content of T-cells in the peripheral blood and the lymph nodes increased, while the number of B-cells in the blood and T gamma-suppressors increased. The subsequent heterologous sensitization with pollen abolished the effect of SIT, inducing the general decrease of the level of T gamma-lymphocytes and enhancing the number of T-lymphocytes in the lymph nodes.

Allergens↗
PubMed1995

Passive immunotherapy in neonatal calves--II. The efficacy of a J5 Escherichia coli hyperimmune plasma as immunotherapy in neonatal calves.

Hyperimmunized bovine plasma containing antibodies to a mutant Escherichia coli O111:B4 (J5) was used to conduct a prospective double-blind clinical trial to evaluate its efficacy as an immunotherapy to bovine neonates in field conditions. Two- to three-day-old calves (N = 150) were randomized into three groups (n = 50) to receive (1) no plasma (NP) or (2) control (traces or no J5 antibody) bovine plasma (CP), or (3) hyperimmune bovine anti J5 plasma (HP) in two subcutaneous total doses of 10 ml kg-1 body weight at a 24 h interval. Various physiological, pathological and clinical parameters of the study subjects were observed up to three weeks while other data such as morbidity, mortality and the effect on heart girth increase were collected up to the end of the eighth week. Weekly serum total protein and immunoglobulin G (IgG) concentrations were preferentially increased from the baseline values in HP calves but not statistically significant (p > 0.05) in group comparison. Mean (geometric) serum J5 ELISA titers in the HP group were significantly (p < 0.001) higher than the other two groups that increased about 1-log by the first week of plasma intervention, followed by a gradual decline by the third week. Out of three total deaths due to septicemia and colitis, one was from the NP group while the other two were from the HP group. Morbidity as measured daily on a 13-point scoring scale were not statistically (p > 0.05) different among the groups. Variation in the mean heart-girth increase was non-significant (p > 0.05) among groups by the eighth week. Higher increase in heart girth was generally associated with higher initial serum IgG (p < 0.01) concentration. Our results suggest that this lot of hyperimmune J5 plasma at this dose was not superior to control plasma or to no intervention in terms of calf morbidity and mortality.

Animals↗
PubMed1990

Evolution of the late asthmatic reaction during immunotherapy and after stopping immunotherapy.

In previous studies it was demonstrated that the frequency and the severity of the late asthmatic reaction (LAR) can be attenuated by immunotherapy (IT). The present study was set up to observe the evolution of the LAR under IT and after having stopped IT. Nineteen children with bronchial asthma and an LAR to house dust mite (Dermatophagoides pteronyssinus) (HDM) were selected for this study. All subjects received IT with HDM extract during 1 year. Thereafter, the children were divided randomly into two groups to receive, double-blind, during a second year, IT with HDM (N = 9) or placebo injections (N = 10). Bronchial challenges were performed after the first and second year. After the first year, a significant decrease in the severity of the LAR was noted in all but one subject (mean decrease of FEV1 before, 40.53% versus after 1 year, 22.95%; p less than 0.0001). After the second year, the severity of the LAR remained the same in the group that received HDM injections during the second year (20.78% versus 23.00%), but in the group that received placebo injections during 1 year, a significant worsening of the LAR was observed after the second year (24.90% versus 31.20%; p = 0.038). From this study it can be concluded that the severity of the LAR decreases after the first year of IT but that the severity of the LAR remains the same after the second year of IT. In children who stop receiving IT after 1 year, we observed a recurrence of the LAR after 1 year to the same level as before IT was started.

Adolescent↗
PubMed1997

Immunotherapy with a standardized Dermatophagoides pteronyssinus extract. VI. Specific immunotherapy prevents the onset of new sensitizations in children.

BACKGROUND: The natural history of allergic sensitization is complex and poorly understood. A prospective nonrandomized study was carried out in a population of asthmatic children younger than 6 years of age whose only allergic sensitivity was to house dust mites (HDMs). OBJECTIVES: The study was designed to determine whether specific immunotherapy (SIT) with standardized allergen extracts could prevent the development of new sensitizations over a 3-year follow-up survey. METHODS: We studied 22 children monosensitized to HDM who were receiving SIT with standardized allergen extracts and 22 other age-matched control subjects who were monosensitized to HDM. The initial investigation included a full clinical history, skin tests with a panel of standardized allergens, and the measurement of allergen-specific IgE, depending on the results of skin tests. Children were followed up on an annual basis for 3 years, and the development of new sensitizations in each group was recorded. RESULTS: Ten of 22 children monosensitized to HDM who were receiving SIT did not have new sensitivities compared with zero of 22 children in the control group (p = 0.001, chi square test). CONCLUSIONS: This study suggests that SIT in children monosensitized to HDM alters the natural course of allergy in preventing the development of new sensitizations.

Animals↗
PubMed2003

Rush venom immunotherapy in patients experiencing recurrent systemic reactions to conventional venom immunotherapy.

BACKGROUND: An unknown number of venom-allergic patients fail to reach the maintenance dose (MD) during the build-up period of conventional venom immunotherapy (VIT) due to recurrent systemic reactions (SRs). OBJECTIVE: To establish an alternative VIT protocol that will enable these patients to reach a full protective MD. METHODS: Venom-allergic patients who had experienced recurrent SRs during the build-up period of conventional VIT underwent rush VIT. RESULTS: Of the 9 patients who participated in this study, the 6 who underwent 8 treatment courses tolerated the rush VIT well and reached the MD within 3 days. In 3 of these patients, mild cutaneous SRs were overcome with loratadine. In 2 patients who experienced recurrent and more severe SRs, the original 3-day rush VIT had to be modified and extended to 5 days until the MD was reached. In a single patient who experienced an anaphylactic reaction, VIT was discontinued. CONCLUSIONS: Rush VIT is an appropriate therapeutic alternative that enables most patients with recurrent SRs throughout the build-up period of conventional VIT to reach a full protective MD.

Anaphylaxis↗
PubMed1988

Immunotherapy with partially purified and standardized tree pollen extracts. III. Specific IgE response to the major allergens of alder, birch and hazel pollen during immunotherapy.

Patients allergic to pollen from alder, birch and hazel were hyposensitized during a 3-year period with either birch pollen extract alone (n = 24) or a mixture of one or more of alder, birch and hazel pollen extracts (n = 27). The effect of the treatment was evaluated by RAST and tandem crossed-radioimmunoelectrophoresis (tandem-CRIE). The patient' specific IgE response to the major allergens of alder (Aln g I), birch (Bet v I) and hazel (Cor a I and Cor a II), as measured by tandem-CRIE, and the total specific IgE response, measured by RAST, decreased significantly (Pc less than 0.05) during immunotherapy, irrespective of the extract used during the treatment. There was no significant difference (Pc less than 0.05) between the two treatment groups. The results obtained indicate either that birch pollen extract alone is adequate in the treatment of the studied patient group or the patients had been sensitized towards birch pollen alone.

Clinical Trials as Topic↗
PubMed1996

Immunotherapy with a standardized Dermatophagoides pteronyssinus extract. V. Duration of the efficacy of immunotherapy after its cessation.

Specific immunotherapy (SIT) using a standardized mite extract is effective and safe when administered under optimal conditions. However, the duration of its effectiveness after cessation of treatment remains unknown. Forty asthmatic subjects who had received SIT with a standardized Dermatophagoides pteronyssinus (Der p) extract under the same protocol were studied. All had received SIT for a period of 12-96 months and were not receiving pharmacologic treatment. The FEV1 was within normal range in all patients. After cessation of treatment, patients were followed for up to 3 years at 6-month intervals. The patient was considered to have relapsed when symptoms of asthma and/or rhinitis occurred and/or when pulmonary function tests were impaired. Skin tests with increasing concentrations of Der p were carried out before and at the end of SIT. Forty-five percent of the patients did not relapse. The duration of efficacy of SIT was related to the duration of SIT itself (P < 0.04). Most patients who did not relapse had a decrease in skin test reactivity at the end of SIT, whereas most patients who relapsed did not show any change (P < 0.003). The duration of efficacy of SIT after its cessation depends upon the duration of SIT and may be predicted by the effect of SIT on skin tests.

Adolescent↗
PubMed2003

Intranasal immunotherapy is more effective than intradermal immunotherapy for the induction of airway allergen tolerance in Th2-sensitized mice.

Immunotherapy (IT) by injection more readily induces clinical tolerance to stinging insects than to respiratory allergens. However, while systemic immunization induces adaptive responses systemically, the induction of mucosal immunity generally requires local Ag exposure. Taken together, these observations suggest that the poor success rate of systemic IT for asthma could be a consequence of inadequate immune modulation in the airways. In support of this position, investigations presented in this report demonstrate that allergen IT more effectively induces airway allergen tolerance in Th2-sensitized mice, when delivered by the intranasal (i.n.) vs the intradermal (i.d.) route. Moreover, compared with native allergen, allergen immunostimulatory sequence oligodeoxynucleotide conjugate proved to be a more effective i.n. IT reagent for protecting allergic mice from airway hypersensitivity responses. Furthermore, for both native allergen and allergen immunostimulatory sequence oligodeoxynucleotide conjugate, i.n. and i.d. IT delivery were similarly effective in modulating systemic immune profiles in Th2-sensitized mice, while only i.n. IT had significant immunomodulatory activity on B and T cell responses in the airways. The present investigations may be the first to suggest that i.n. IT is more effective than i.d. IT for the treatment of asthma. Furthermore, our results suggest that modulating airway rather than systemic immunity may be the more important therapeutic target for the induction of clinical tolerance to respiratory allergens.

Adjuvants, Immunologic↗
PubMed1981

Adoptive immunotherapy and combined chemo-immunotherapy in transplantable leukaemia of AKR mice (TAL); occurrence of natural killers.

Allo- and syngeneic lymphoid effector cells were injected I. P. into transplantable leukaemia (TAL)-bearing AKR recipients. Effector cells were collected from the peritoneal cavity, lymph nodes, spleen, or thymus, of either non-immunized donors or of donors previously immunized with TAL cells. The ratio, injected number of effector cells divided by injected number of TAL target cells varied in individual experiments from 10:1 to 10 000 : 1. Some AKR recipients were given prior to the leukaemia inoculation a whole-body sublethal X-ray irradiation and/or an I.P. injection of cyclophosphamide. Mean survival of TAL leukaemia was most often prolonged in recipients given viable allogeneic thymocytes derived from non-immunized donors. In some leukaemia-bearing mice treated with chemo-immunotherapy, permanent survival (greater than 70 days) could be observed. As a rule, effector cells derived from non-immunized allogeneic donors were more effective than effector cells from the immunized areas. Syngeneic effectors were ineffective. The occurrence of natural killers (NK cells) to Gross virus-infected cells in the lymphoid organs of low-leukaemic inbred mouse strains is postulated. These NK cells are lacking in high-leukaemic AKR mice.

Animals↗
PubMed1998

[Specific immunotherapy using allergens apropos of specific immunotherapy by the sublingual route].

The present number of publications an allergen specific immunotherapy (ITa) by clinically controlled tests, double blind, is objective proof of the value of this treatment in the allergy pathologies mediated by IgE. The mechanisms of action of Ita are better understood, taking account of the intervention of TH2 and TH1 cells with the respective involvement of cytokines IL4-IL5, favouring the synthesis of IgE and interferon gamma (IFN gamma) slowing the synthesis of IgE. Adjuvants of bacterial origin influence the balance TH2/TH1 by blocking the production of TH2 cells. Ita by the sublingual route (SLIT) has been the objective of double blind clinical studies, with favourable results and good tolerance, of a number of allergens, pollens (grass, ragweed, parietaria, olive) and D. pteronyssinus mites. Application of this technique of SLIT to foods and drugs reveals more a mechanism of customisation than induction of cellular acticity, of a mucosal secretory IgA and an oral tolerance with systemic response, mechanisms that are involved in SLIT. Taking into account the restrictions of ITa, SLIT allows inclusion of other allergic patients, such as children receiving injections and subjects who are not inclined to observe and comply with treatment.... The different techniques used for classical ITa by the subcutaneous route are also useable for SLIT with a very good tolerance, apart from some transitory digestive problems. SLIT is no longer a technique of the future, but already one of the present time, currently used and which gives a renewal of value in the form of therapy that is ITa for IgE-mediated allergy pathology.

Administration, Sublingual↗
PubMed2003

Phase I immunotherapy with a modified vaccinia virus (MVA) expressing human MUC1 as antigen-specific immunotherapy in patients with MUC1-positive advanced cancer.

BACKGROUND: The MUC1 protein is a highly glycosylated mucin normally found at the apical surface of mucin-secreting epithelial cells in many types of tissues. MUC1 is expressed, but heavily underglycosylated, in different human tumors. TG4010 is a viral suspension of a recombinant vaccinia vector (MVA) containing DNA sequences coding for the human MUC1 antigen and interleukin-2 (IL-2). This product was developed for use as a vaccine in cancer patients whose tumors express the MUC1 antigen. The objective of the present study was to determine the safety of the product and to define the dose of TG4010 to be used in further clinical trials. MATERIALS AND METHODS: Thirteen patients with different solid tumors were treated by repeated intramuscular injection with increasing doses of TG4010 in two separate phase I studies, one in Europe (Basel-CR) and one in the United States (UCLA-RF): a total of 6 patients were treated at a dose of 5 x 10(6) pfu, 3 patients at 5 x 10(7) pfu, and 4 patients at 10(8) pfu. Safety, efficacy, and different immunological tests were the endpoints of the study. RESULTS: Tolerance of TG4010 was excellent, and side effects mainly consisted of injection site pain and influenza-like symptoms. There was no apparent detrimental effect of repeated injections of the vaccinia virus. Four of thirteen evaluable patients showed stabilization of their disease for 6 to 9 months. One lung cancer patient who was initially progressing after the first injections later showed a marked decrease in the size of his metastases that lasted for 14 months. Some T cell proliferative immune responses were seen in five patients. CONCLUSIONS: The administration of TG4010 was generally well tolerated in patients with metastatic tumors, and transient disease stabilization was observed in several patients, warranting further clinical studies with the product.

Antineoplastic Agents↗
PubMed1990

Trial of anticancer immunotherapy with immobilized pokeweed mitogen: immunotherapy by extracorporeal circulation.

For the purpose of activating the immune system in the living body, we made use of pokeweed mitogen (PWM). PWM, a type of lectin, has the potential to induce anticancer cells. In order to utilize this potential and apply it to cancer therapy by hemoperfusion with PWM, the lectin is immobilized on the surface of synthetic polymer beads and these beads are packed into a minicolumn. Human peripheral lymphocytes were activated by circulatory contact stimulation through the PWM column for 1h. After circulatory contact stimulation through the column, lymphocytes were collected and used as effector cells. Cytotoxicity tests were measured by 51Cr-release assay using K-562 cells and Daudi cells for targets. This material could enhance natural killer activity and induce cytotoxicity against natural-killer-resistant Daudi cells. Lymphocytes activated by the PWM column were injected intraregionally into nude mice bearing MKN-1 tumor, and suppression of tumor growth was recognized. Anticancer activities by direct hemoperfusion treatment with a PWM minicolumn were examined in Vx2-tumor-bearing rabbits. A single treatment using the PWM column was performed 6 days after tumor inoculation. Suppression of the tumor growth was observable for 25 days. PWM minicolumns are a likely anticancer material, acting as immunomodulators.

Animals↗