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PubMed1992

Immunotherapy of murine transitional cell carcinoma of the bladder using alpha and gamma interferon in combination with other forms of immunotherapy.

BCG immunotherapy is very effective in the treatment of superficial transitional cell carcinoma of the bladder, but its significant toxicity may limit its use in some patients. In an effort to find less toxic and potentially more effective treatments we investigated the possible immunotherapeutic potential of combinations of Alpha Interferon (1000 IU) and Gamma Interferon (500 IU) with bacillus Calmette Guerin (BCG) (10(7) cfu), Interleukin-2 (4000 IU), and Keyhole Limpet Hemocyanin (50 micrograms.) in the MBT2 murine bladder cancer model. Significant reductions (p less than 0.05) in tumor incidence relative to the saline control, 83%, Day 35) was observed in groups receiving alpha interferon (42%), Keyhole limpet hemocyanin (42%), interleukin-2 (25%), alpha interferon + Keyhole limpet hemocyanin (17%), alpha interferon + interleukin-2 (33%), gamma interferon + BCG (42%), and gamma interferon + interleukin-2 (17%). All treatment groups with the exception of the group receiving gamma interferon had significantly reduced tumor volume (p less than 0.05) relative to the saline control. Combination treatment groups were significantly more effective than single agent treatments (p = 0.0057). The exhibited anti-tumor effect of these immunotherapeutic agents alone and in combination suggest that they may prove to be effective forms of immunotherapy for transitional cell carcinoma of the bladder.

Animals↗
PubMed2001

Classic specific immunotherapy and new perspectives in specific immunotherapy for food allergy.

Food allergy is a major cause of life-threatening hypersensitivity reactions. Food-induced anaphylaxis is the most common reason for someone to present to the emergency department for an anaphylactic reaction. The avoidance of the allergenic food is the only method of preventing further reactions that is currently available for sensitized patients. Strict avoidance of specific foods is the accepted treatment of food-induced allergic reactions but is often an unrealistic therapeutic option for food-induced hypersensitivity reactions for the many reasons previously described. Desirable therapeutic strategies for the treatment and prevention of food allergies must be safe, relatively inexpensive and easily administered. Recent advances in the understanding of the immunological mechanisms underlying allergic disease and better characterization of food allergens have greatly expanded the potential therapeutic options for future use. Several different forms of immunomodulatory therapies are currently under investigation: peptide immunotherapy, mutated protein immunotherapy, allergen DNA immunization, vaccination with immunostimulatory DNA sequences and anti-immunoglobulin E (Anti-IgE) therapy.

Desensitization, Immunologic↗
PubMed2003

A translational bridge to cancer immunotherapy: exploiting costimulation and target antigens for active and passive T cell immunotherapy.

Building on significant advances in basic tumor immunology over the past decade, current translational efforts to develop novel antitumor T cell therapeutics continue to accelerate. Both passive T cell immunotherapy (e.g., adoptive T cell transfusions) and active immunotherapy (e.g., vaccination) may eventually become part of the arsenal to treat cancer. Successful approaches will need to repair host immunoincompetence in T cell function, circumvent immunosuppressive factors of the tumor microenvironment, and optimize target antigens with regard to clinical applicability, autoimmunity, and risk of antigen mutation. Here, we characterize two model systems for the ex vivo activation and expansion of human T lymphocytes and describe the potential for providing broadly applicable antitumor specificity by targeting universal tumor antigens. Polyclonal CD4+ T lymphocytes can be activated and expanded using anti-CD3 and anti-CD28 antibodies presented on magnetic beads, and CD8+T lymphocytes can be successfully expanded using a novel genetically engineered cell-based technology that presents anti-CD3 and anti-CD28 along with the costimulatory molecule CD137 (4-1BBL). As the prototypical and best-described universal tumor antigen, the human telomerase reverse transcriptase hTERT is vastly overexpressed in human tumors but absent in most normal tissues. Cytotoxic T lymphocytes (CTL) recognize peptides derived from hTERT and kill hTERT-positive tumor cells of multiple histologies. Phase I trials translating these discoveries to novel active and passive T cell therapies have been initiated, with an eye toward combining these strategies once safety is established.

Animals↗
PubMed2006

Non-injection routes for allergen immunotherapy: focus on sublingual immunotherapy.

Allergen specific immunotherapy, together with drugs and allergen avoidance, is a cornerstone in the management of respiratory allergy. The non-injection or local routes were developed with the main goal of improving the safety and minimizing the risk of those side effects, which can accompany the injection route. The pure oral route and the bronchial route showed, in the clinical trials, only a marginal efficacy with not negligible side effects. Therefore, these routes are no longer recommended for clinical use. The nasal route proved effective and safe, but its efficacy is strictly limited to the nose. Moreover, the practical problems with administration have made the use of nasal immunotherapy progressively declining. The efficacy of the sublingual route is confirmed by numerous controlled trials, and a meta analysis (in allergic rhinitis). The safety profile, as derived from clinical trials and post marketing surveillance studies, is satisfactory, with mild gastrointestinal complaints being the more frequent side effect reported. Recent studies have also demonstrated that SLIT has a long-lasting effect and a preventive effect on the onset of new skin sensitizations, and interesting data on adherence and mechanisms of action have become recently available. Based on these experimental data, SLIT is now officially accepted as a viable alternative to the subcutaneous route in adults and children. Several points still need to be elucidated, including: mechanisms of action, optimal dosages, and indications in pediatric patients.

Administration, Inhalation↗
PubMed1990

[Study on adoptive immunotherapy in patients with renal cell carcinoma. II. Plasmapheresis with adoptive immunotherapy using LAK cells and IL-2].

The existence of immunosuppressive factors which impair the clinical effect of treatment using IL-2 or lymphokine activated killer (LAK) cells has been reported in the serum of patients with renal cell carcinoma. For the purpose of eliminating these immunosuppressive factors, plasmapheresis combined with adoptive immunotherapy using LAK cells was performed in ten patients with stage IV renal cell carcinoma. Immunological examinations revealed that the number of peripheral blood lymphocytes, NK activity and the ratio of Leu 11 positive cells were increased during the treatment. Of the 9 evaluable patients, one has a partial response, 5 showed no change and 3 had progressive disease. In addition to the one partial response, the size of some metastatic lesions in the lungs decreased in 2 patients during the treatment. As serious side effects, brain edema progressed in 2 patients with brain metastases and acute hepatitis due to plasmapheresis was noted in one patient. Moreover, transient and reversible renal dysfunction developed in most patients. These results indicated that plasmapheresis combined with adoptive immunotherapy using LAK cells is a useful therapy for patients with advanced renal cell carcinoma.

Adult↗
PubMed1998

[Immunology in clinical practice. XVII. Immunotherapy of metastatic renal cell carcinoma. Work Group Immunotherapy, Dutch Oncology].

Metastatic renal cell carcinoma has a poor prognosis. The efficacy of immunotherapy with interferon alpha (IFN-alpha) or interleukin 2 (IL-2) or their combination has been investigated extensively. The best schedule and optimum dose and combination is not known. On the basis of three prognostic factors, viz. WHO performance score, time between initial diagnosis and treatment of metastases, and number of metastatic sites, patients can be divided in prognostic groups. Patients classified in the favourable or intermediate prognostic group may survive longer after immunotherapy and therefore are candidates for such therapy. Patients who are classified in the poor prognostic group will not profit from any known systemic therapy.

Antineoplastic Agents↗
PubMed1999

Immunotherapy with Mycobacterium vaccae in patients with newly diagnosed pulmonary tuberculosis: a randomised controlled trial. Durban Immunotherapy Trial Group.

BACKGROUND: Mycobacterium vaccae, an environmental saprophyte, has immunogenic properties that enhance the host immune response. Immunotherapy with M. vaccae has been suggested to shorten short-course antituberculosis chemotherapy. We tested the hypothesis that the addition of M. vaccae to standard short-course antituberculosis chemotherapy would decrease the time to achieve a negative sputum culture. METHODS: Patients with newly diagnosed tuberculosis were randomly assigned an injection of saline (placebo) or M. vaccae on day 8. All patients received antituberculosis chemotherapy with rifampicin, isoniazid, pyrazinamide, and ethambutol. Sputum samples were checked by microscopy and culture every week for the first 8 weeks and monthly until the end of chemotherapy at 6 months. The primary outcome was the time to a negative sputum culture in the first 8 weeks. Intention-to-treat analysis was used and time to sputum clearance was assessed by log-rank test and Cox's proportional-hazards regression. FINDINGS: 172 patients received M. vaccae and 175 patients received placebo. At 8 weeks, 70 patients in the M. vaccae group and 65 patients in the placebo group had a negative culture; there was no difference between groups in the time to a negative culture (p=0.83). There was no interaction between HIV status and treatment. INTERPRETATION: M. vaccae immunotherapy has no benefit when added to standard antituberculosis chemotherapy.

AIDS-Related Opportunistic Infections↗
PubMed1990

[Neonatal sepsis: bases and possibilities for immunotherapy and immunoprophylaxis. 2: Immunotherapy].

The physiological immunodeficiency of preterm and term newborns is the major cause of their increased susceptibility to infections. Although nonspecific and specific host defence mechanisms are morphologically intact, there are functional and quantitative defects. Supportive immunotherapy is required to equalize these immunological defects. This article reviews topical possibilities for immunotherapy of neonatal sepsis (exchange transfusion, transfusion of fresh blood or fresh plasma, granulocyte transfusion, use of immunoglobulins, fibronectin, interferon and colony-stimulating factor).

Bacterial Infections↗
PubMed1979

Adoptive immunotherapy and chemo-immunotherapy in murine L-1210 leukemia and its influence on the kinetics of leukemic proliferation.

Donor allogeneic C57Bl/6 lymphoid cells from peritoneal cavity, lymph nodes, thymus and spleen of immunized and non-immunized mice were used for adoptive immunotherapy of L-1210 ascites leukemia in DBA/2J recipients. Donor effector cells were injected i.p. into leukemic mice which were given a whole-body irradiation in a dose of 300 r X-rays prior to leukemia inoculation. The in vitro cytotoxicity of the effector cells was tested by the LT- and 51Cr-tests. Cytokinetics of leukemia undergoing therapy was followed by impulse-cytophotometry. An adoptive chemo-immunotherapy with the aid of peritoneal or splenic lymphoid cells from immunized donors proved to be most effective. The cells were injected on the second day into recipients inoculated with leukemia on the day 0, and then given on the first day a single i.p. injection of cyclophosphamide in a dose of 50 mg/kg body weight. Under these conditions the secondary disease did not influence therapy and apart from a distinctly prolonged survival there was also noted a number of permanent survivals of leukemia. It was also found that peritoneal and splenic lymphoid cells of immunized donors exhibited most pronounced direct and indirect cytotoxicity against target cells in vitro. In vivo, the effector cells mounted an attack on the L-1210 cells probably at the onset of the G1-phase of the cell cycle.

Animals↗
PubMed1987

Double-blind, placebo-controlled immunotherapy with mixed grass-pollen allergoids. I. Rush immunotherapy with allergoids and standardized orchard grass-pollen extract.

Forty-five grass pollen-allergic patients were randomly assigned to three groups according to their skin test and RAST sensitivities and the severity of seasonal rhinitis. Eleven patients were treated with placebo (group 1), 19 patients (group 2) were treated with a six-mixed grass-pollen allergoid prepared by mild formalinization with a two-step procedure, and 15 other patients were treated with a standardized orchard grass-pollen extract (group 3). Because of a different immunotherapy schedule, only patients placed in groups 1 and 2 received the extracts in a double-blind fashion. Rush immunotherapy was performed in 3 to 6 days, and the maintenance dose was subsequently administered weekly for 4 weeks and every 2 weeks until the end of the grass-pollen season. During the season, a coseasonal treatment was administered. Systemic reactions occurred during the rush protocol in 36.8% of patients treated with allergoid and 20% of patients who received the standardized extract. Only patients treated with allergoid had systemic reactions during maintenance dose. The reactions observed with the standardized extract were more severe. Total doses of allergoid ranged from 2350 to 13,500 protein nitrogen units. Symptoms and medication scores during the peak of the season were analyzed. Patients treated with the standardized allergen had a significant reduction of the number of days of symptoms during the month of June (9.5 +/- 6.7 days; p less than 0.005) and of medication scores (1.3 +/- 1.4; p less than 0.01) compared to patients receiving placebo (19.4 +/- 8.1 days; medication score, 2.8 +/- 2.1).(ABSTRACT TRUNCATED AT 250 WORDS)

Allergens↗
PubMedDate not supplied

Local conjunctival immunotherapy: the effect of dermatophagoides pteronyssinus local conjunctival immunotherapy on conjunctival provocation test in patients with allergic conjunctivitis.

BACKGROUND: We evaluated the effect of local conjunctival immunotherapy (LCIT) with standardized dermatophagoides pteronyssinus (Dp) extracts on antigen-specific conjunctival provocation test (CPT) in patients with allergic conjunctivitis in a double blind, placebo-controlled study. We use the CPT because in our experience is the more objective parameter to evaluate the sensitivity to allergens in this patients. METHODS: The patients were selected on the basis of symptoms, positive prick test, positive CPT and elevated serum and tears total and specific IgE. The CPT was assessed with increased dilution of Dp extracts instilled into the lower fornix. Conjunctival hyperemia, tearing, itching, burning and swelling of eyelids were scored according a 4-point rating scale. Patients were randomly assigned to 2 groups of 12. The first group was treated with Dp extracts and the second group with placebo during 6 months. A drop of diluted antigen was instilled in both eyes daily, in 2-fold increased concentrations, the first 10 AU/ml. The maintenance dose was 1,000 AU/ml or the maximal dose which did not provoke symptoms. The symptoms were controlled with oral and/or local antihistamines. We evaluated the CPT before and after the treatment. The patients did not receive antihistamines during the 15 previous days to carrying-out the CPT. RESULTS: Ten of the twelve patients of the active group complete the treatment. One of the patients dropped out of the study because experienced local reaction with a dose of 1,000 AU/ml and refused to continue with the treatment. Other patient was disqualified for failure to comply with the protocol. One patient, which experienced itching and tearing with a dose of 1,000 AU/ml, tolerate 100 AU/ml. We continue with this dose until the end of treatment. The remaining patients tolerate 1,000 AU/ml as maintenance dose. A significant difference was observed in the score of CPT between LCIT treated patients and placebo group after 6 month of LCIT. CONCLUSIONS: We propose LCIT as a useful alternative to traditional subcutaneous immunotherapy in patients with allergic conjunctivitis.

Adolescent↗
PubMed1991

Local immunotherapy by inhalation of a powder extract in asthma due to house dust mite Dermatophagoides pteronyssinus: a double-blind comparison with parenteral immunotherapy.

To verify the efficacy and the tolerability of local immunotherapy (LI) by inhalation of a powder extract of house dust mite (HDM), in comparison with parenteral immunotherapy (PI) by injection, 10 patients with asthma due to HDM were studied in a blind fashion. 5 patients (Group A) underwent LI and subcutaneous injections of placebo, 5 patients (Group B) underwent PI and inhalation of lactose for 6 months. In both groups each inhalation was preceded by premedication with disodium cromoglycate (DSCG) (40 mg). In Group A a significant decrease in symptoms score and in peak expiratory flow (PEF)-derived parameters was observed already after 3 months of treatment, and 2 patients lost the late component of the bronchial response to the challenge with HDM. No significant variation was found in bronchial responsiveness to methacholine and ultrasonically nebulized distilled water (UNDW) and in immunologic humoral and cellular parameters in peripheral blood after treatment in either group. No local important adverse reactions were observed in Group A and no systemic side effects were observed in either group. We conclude that LI is as effective as PI, but more rapid in its action, in the treatment of asthma due to HDM. Moreover, LI is locally well tolerated, providing DSCG is inhaled before each therapeutic inhalation, and does not induce systemic side effects.

Administration, Inhalation↗
PubMed1977

[Immunotherapy of warts. Is it an experimental model for cancer immunotherapy?].

The warts produced by virus Papova, provedly cancerous, have immunological characteristics that allow to establish some analogies with cancer. Its immunotherapy is studied with levamisole and by means of a delayed immunity reaction "in situ" with regulated intensity. The level of delayed immunity in the patient with warts is established by quantitative DNCB test, finding that the same is impaired in 60% of men and 87% of women. The levamisol therapy cures 54% of warts. The patients that not cure but improve their delayed immunity level after the treatment with levamisol, are submitted to external application of DNCB, using a concentration calculated on the quantitative test results. With regard to their delayed immunity we introduce a new group of patients: the hiperergic type or reactive to 2,5 microgram of DNCB that cures their warts by the sole action of the test. Once obtained the curve of the distribution of delayed immunity values in the warts population before and after the levamisole therapy, we observe that the first is identical to that of cancer patients. In view of the tight relation among diseases with impaired delayed immunity, such as warts, herpes, aphtas, piodermitis and cancer (residual or postsurgical), we propose the same management, control and immunotherapy for all of them.

Clinical Trials as Topic↗
PubMedDate not supplied

Specific immunotherapy in pollinosis: I. Valuation of certain cytoimmunological indicators over the course of four years of immunotherapy in pollinosis.

The aim of this study was to identify, based on a wide range of cytoimmunological and immunological tests in combination with clinical valuations, the changes which occurred in pollinosis over the course of specific immunotherapy after the first, second, third and fourth years of treatment. Further tests were also conducted in order to demonstrate which of the indicators tested for correlated to a clinical improvement and might thus be helpful in determining the effectiveness of treatments for pollinosis. A group of 167 individuals, including subjects who had just completed their first, second, third and fourth year of desensitization treatments were tested. Levels of IgA, IgM, IgG, IgD, total and specific IgE, T-RFC, B-EAC, T-FcM-EN and T-FcG-BG lymphocyte counts, and concentrations of basal, total and specifically released blood histamine were all determined and noted. It was ascertained that the indicators best correlating to a clinical improvement over 4 years of desensitization in pollinosis were specific and total IgE, as well as the percentage of specifically released histamine present in the blood, with the level of basal histamine in the blood being constant during the entire course of the treatment. The remaining indicators which were tested did not undergo any characteristic changes over the course of 4 years of immunotherapy.

Adult↗
PubMedDate not supplied

Specific immunotherapy in pollinosis: II. Forecasting changes in certain cytoimmunological indicators after four years of immunotherapy in pollinosis.

The determination of an appropriate period of duration for specific immunotherapy presents an important problem in the treatment of allergic diseases. The aim of this paper was to conduct a prognostic study of certain immunological indicators after 4 years of desensitization, and to determine which of the tested indicators are characteristic for an evaluation of the clinical condition. Individuals with pollinosis were tested after the first, second, third and fourth year of desensitization using the pollen allergen. The B and T-lymphocyte counts, the levels of immunoglobulins A, M, G, and total and specific E, and the volume of basal, total and specifically released histamine were all measured. Furthermore, the clinical condition of the patient was defined using a score method (0-3 points), taking into account the results of testing and the basic symptoms of the disease. Following this, a prediction of results after the fifth year of desensitization was made, using Brown's method of exponential smoothing. The majority of the data obtained from the forecasting study indicate that in the subsequent fifth year of desensitization, the indicators studied should undergo further changes in values, offering a strong argument for the necessity of extending the period of immunotherapy in pollinosis beyond three years. In the results of the regression function estimates it was determined that, among the indicators studied, those which are helpful in monitoring treatment are: T-RFC, T-FcG-BG, T-FcM-EN and B-EAC lymphocyte counts, levels of IgA, IgM and specific IgE, and the percentage of specifically released histamine.

Adult↗
PubMed1991

[Immunotherapy of tumors: from the first experimental studies to the recent clinical applications. I. Passive immunotherapy].

After a short introduction on the rationale of cancer Immunotherapy (IT), the Authors analyse the experimental and clinical treatments. Very interesting the results of the clinical trials with cells, used with success never reached before with the standards treatments. Particular emphasis has been dedicated to Lymphokine Activated Killers in association with Interleukin2 (IL2) and Tumor Infiltrating Lymphocytes, which have shown a very strong and specific anticancer activity. The encouraging therapeutical possibilities of the association with cytokines and immunosuppressors are also underlined. Monoclonal antibodies are considered a promising therapeutical approach which did'nt receive an effective clinical application, although their use as immunoconjugates with toxines chemotherapeutical and radioactive agents is giving incouraging results. Yet some technical and immunological problems remain to be solved for them to be used in the clinical setting against solid tumors.

Antibodies↗
PubMed1987

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

The effectiveness of immunotherapy using a streptococcal preparation, OK-432, was evaluated for cervical cancer. The 382 eligible patients were stratified by presence/absence of surgical operation and clinical stage, and then, in each stratum, were randomly divided into two groups: an OK-432 treatment group and a control treatment group. The 3-year recurrence-free rates of 221 patients in the OK-432 group and 161 patients in the control group were 71.9% and 58.6%, respectively. The intergroup difference was statistically significant (P less than 0.05). Delayed skin reactions to phytohemagglutinin (PHA) and Su-polysaccharide extracted from Streptococcus pyogenes Su-strain (Su-PS) and peripheral lymphocyte counts were reduced within two months after the initiation of therapy in both groups. The observed immunological changes were apparently reversed by 3 months after the start of the therapy in the OK-432 group, but this took at least one year in the control group, with significant intergroup differences at 6 and 12 months of the therapy (P less than 0.01). These results indicate that OK-432 can be considered as one of the most effective and useful immunotherapeutic agents for cervical cancer.

Biological Products↗
PubMed1996

Immunotherapy III: Combinatorial molecular immunotherapy--a synthesis and suggestions.

Animal models have clearly shown that tumor cells may be amenable to molecular manipulation which can result in immune activation and rejection of unmodified cells (Chapters 4 and 5). The challenge now is to design clinical trials which have a realistic chance of success, (although the definition of 'success' is itself an important issue [see Chapter 9]. How should such a strategy be formulated? A review of the previous fifteen years since the first (immune) gene transfer studies were reported, encompasses a great wealth of data. Unfortunately, far from crystallising a set of unifying principles, these diverse reports shroud us in a fog of uncertainty as to how best to proceed. However, if this technology is to have practical, widespread application in the treatment of cancer patients, it is necessary to identify certain critical immunological goals which any protocols should achieve. Clear elucidation of these goals, by unifying the huge amount of disparate experimental data, must eventually be accomplished. In this chapter, we have reviewed the literature covering the era of molecular immunotherapy. We propose four general goals around which widely applicable clinical protocols, not necessarily dependent upon tumour type or experimental bias, might be based and suggest how they may be achieved in the context of gene transfer.

Animals↗