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PubMed1989

Suppression of the late cutaneous response by immunotherapy.

In a prospective, double-blind, placebo-controlled study, we examined the effect of mountain cedar (MC) immunotherapy on the MC-induced late cutaneous response (LCR). Fourteen MC-sensitive patients were intradermally skin tested before and after immunotherapy with MC extract. We measured the size of the wheal at 15 minutes and the area of tissue swelling at 6 hours. Patients were matched by the size of the LCR and started receiving either MC immunotherapy or placebo immunotherapy. MC-specific immunoglobulins (MC sIgG, MC sIgG1, MC sIgG4, and MC sIgE) were measured by ELISA. Symptom-medication scores (SMSs) were recorded on a daily basis during the MC season and tabulated at the end of the study. Comparison of the 14 paired patients revealed no significant differences between MC-treated and placebo-treated groups in preimmunotherapy MC sIgG1 and SIgG4. However, when MC immunotherapy was compared to placebo immunotherapy, patients receiving MC immunotherapy developed significantly higher MC sIgG1 (p less than 0.04) and MC sIgG4 (p less than 0.01) after immunotherapy. Patients receiving MC immunotherapy also demonstrated significantly greater suppression of the LCR after immunotherapy (p less than 0.005) with the postimmunotherapy LCR correlating significantly with both MC sIgG4 (rs = 0.715; p = 0.008) and cumulative dose of MC received (rs = 0.808; p = 0.004). MC sIgE was similar in both groups after immunotherapy. The reduction in SMSs in the MC-treated group did not reach significance, nor was there a correlation of SMSs with MC sIgE, sIgG, sIgG1, or sIgG4.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed2002

Current opinion of immunotherapy for ocular allergy.

PURPOSE OF REVIEW: Allergic conjunctivitis is common and may be the most prominent or the only feature of allergies. Immunotherapy has been used as a primary treatment for allergies since the early 1900s. Currently the use of immunotherapy for allergic rhinoconjunctivitis is well established and has been shown to decrease the development of bronchial hyperreactivity and asthma. However, the role of immunotherapy for primary treatment of allergic conjunctivitis is unclear. We reviewed the studies where immunotherapy was used with particular attention to the affects on ocular allergies. RECENT FINDINGS: There are many schedules and methods of delivering immunotherapy. Recent studies have started to assess ocular symptoms as one of the parameters to monitor efficacy of therapy. They follow the affects of immunotherapy on conjunctival provocation tests, ocular symptoms, or the use of eye drops. The literature suggests that using the various immunotherapy modalities at different schedules, ocular symptoms improved even when immunotherapy was used on a rush schedule. SUMMARY: The initiation of immunotherapy for allergic rhinoconjunctivitis has been shown to switch the immune response to T helper 1 and thus avoid the progression of other atopic conditions. Current literature shows that using many allergens with different forms of immunotherapy appear to have a significant improvement in ocular allergy symptoms and this can be achieved rapidly and safely in most patients. Whether using immunotherapy early in allergic conjunctivitis will alter the progression of other atopic conditions remains to be investigated.

Allergens↗
PubMed1997

Nasal immunotherapy in pollen-sensitive children.

UNLABELLED: Subcutaneous specific immunotherapy has a considerable risk of side effects, including severe life-threatening ones or even death. The disadvantages and problems of this kind of therapy gave rise to looking for new ways of hyposensitization. In allergic rhinitis the local (nasal) immunotherapy may be effective. We studied the efficacy of local nasal immunotherapy (Allerkin) in grass and ragweed allergic children suffering from seasonal atopic rhinitis. PATIENTS: 36 children (12 with grass pollen, 12 with ragweed pollen immunotherapy, 12 controls). METHODS: nasal provocation tests with increasing doses of Allerkin, skin prick test, diary cards. Schedule of the investigations: enrollment of the patients and nasal provocation tests; grass pollen and ragweed pollen preseasonal immunotherapy with increasing doses of Allerkin; during pollen season registration by symptoms and drug consumption; after the season nasal provocation tests. RESULTS: grass immunotherapy: nasal provocation threshold increased (P < 0.01), symptoms became fewer (P < 0.01) and drug consumption was less in the active group compared to control. Similar but less expressed tendencies were seen in the ragweed group. After the second year of immunotherapy the need for steroid treatment was significantly (P < 0.05) fewer in the immunotherapy group than in the control group. No side effects appeared during the course of immunotherapy, but some patients suffered from mild sneezing or nasal discharge after the Allerkin application. CONCLUSION: local (nasal) immunotherapy is an effective, safe and not troublesome alternative to systemic immunotherapy.

Administration, Intranasal↗
PubMed1994

The appropriate use of skin testing and allergen immunotherapy in young children.

Immunotherapy is clearly effective in the treatment of allergic rhinitis and Hymenoptera sensitivity and probably effective in the treatment of asthma. Few studies evaluate the risks and benefits of immunotherapy in young children. Current evidence suggests that young children are at increased risk for systemic reactions from immunotherapy. Furthermore, immunotherapy or adverse reactions resulting from immunotherapy may result in significant psychologic problems. The potential risks of immunotherapy would be justified if immunotherapy were demonstrated to be safe and additive to other therapies. Immunotherapy might be particularly effective in treating or helping to prevent house dust mite- or cockroach-associated asthma. Until the efficacy of immunotherapy is demonstrated in young children, we agree with the European Academy of Allergology and Clinical Immunology position that immunotherapy in young children is relatively contraindicated.

Allergens↗
PubMed1998

Discontinuing venom immunotherapy: extended observations.

BACKGROUND: Our studies of discontinuing venom immunotherapy after at least 5 years have led to the conclusion that the residual risk of a systemic reaction to a sting was in the range of 5% to 10% in adults, and no severe or life-threatening reaction occurred with 270 challenge stings in 74 patients after 1 to 5 years without venom immunotherapy. OBJECTIVE: The objective of this study was to extend our observation of patients who discontinue venom immunotherapy over 5 to 10 years and to determine which patients are at higher risk for a reaction. METHODS: Patients who discontinued venom immunotherapy were surveyed for 3 consecutive years to determine the frequency of systemic reactions to field stings and the fate of venom sensitivity. The evaluation included the 74 patients previously studied (group 1) and 51 additional patients followed after stopping therapy in our clinical center (group 2). RESULTS: Of the original 74 patients, 11 had field stings again after 3 to 7 years without venom immunotherapy, with one systemic reaction (dyspnea). Of the 51 patients in the other group, 15 were stung, of whom four (26%) had systemic reactions, including respiratory symptoms requiring epinephrine. Review of group 1 and group 2 revealed that half of the patients who had systemic reactions to a sting after stopping venom immunotherapy had a history of a systemic reaction occurring during venom immunotherapy (to an injection or a sting). Systemic reactions occurred in three patients who had negative skin test reactions; all three had very low but detectable venom-specific serum IgE antibody levels as determined by RAST and had a history of systemic reactions during venom immunotherapy. Greater severity of the pretreatment reaction was not associated with higher frequency of reaction to stings after stopping therapy but was associated with greater severity if a reaction did occur. CONCLUSIONS: Venom immunotherapy (yellow jacket/mixed vespid) in adults can be discontinued after 5 to 6 years with a 5% to 10% residual risk of a systemic reaction. Risk factors may include history of a systemic reaction during venom immunotherapy, persistent strongly positive skin test sensitivity, and the severity of the pretreatment reaction.

Adult↗
PubMed1996

Immunotherapy for childhood asthma: is there a rationale for its use?

OBJECTIVE: This paper reviews the literature regarding immunotherapy in the management of childhood asthma. Immunotherapy is a well established treatment of venom allergy and allergic rhinitis, however its use in asthma remains controversial. DATA SOURCES: We reviewed the pediatric literature from 1966 to 1994 and evaluated the existing studies for clinical efficacy of immunotherapy in childhood asthma. STUDY SELECTION: Only 12 purely pediatric studies existed over the time period that we reviewed. The studies used a variety of different antigens including house dust, house dust mite, grass, mold, cat, dog, and combinations of antigens. RESULTS: In reviewing the studies, we assessed study duration, number of subjects, whether it was blinded, placebo controlled or open labeled, the measures of clinical efficacy and the assessments of specific and nonspecific bronchial reactivity. The studies were very heterogeneous, and therefore direct comparison and extrapolation of conclusions was difficult. The majority of the studies demonstrated either an improvement in asthmatic symptoms or a decrease in bronchial reactivity to the specific antigen employed, or both. The minority of studies demonstrated no clinical efficacy. The most consistent evidence of benefit was suggested in those trials employing house dust mite therapy, while immunotherapy for grass and cats demonstrated some benefit but the number of studies employing these treatments was very small. There are no trials that provide convincing evidence that immunotherapy with dog and mold antigens is effective for childhood reactive airway disease. CONCLUSION: Asthma is a multifactorial disease with many triggers. In establishing a role for immunotherapy one must consider all the different aspects such as allergic triggers, environmental stresses, and viral infections. The literature is unclear as to when immunotherapy should be initiated for childhood asthma. While there are suggestions that immunotherapy should be considered for the child with mild or moderate asthma and dust mite sensitivity when pharmacotherapy is not efficacious, the immunomodulatory properties of immunotherapy may actually be more tailored for early intervention in asthma rather than for use once symptoms have occurred. More research is required in order to clarify whether immunotherapy should be recommended more often for the treatment of childhood asthma.

Asthma↗
PubMed1996

Efficacy of immunotherapy to ragweed antigen tested by controlled antigen exposure.

BACKGROUND: Immunotherapy is a recognized component in the management of allergic rhinitis. Its efficacy has been evaluated in a number of clinical field trials. These methods of evaluation are limited by control of antigen exposure. OBJECTIVE: A study was designed to evaluate the efficacy of immunotherapy in ragweed-induced rhinoconjunctivitis using an environmental exposure unit. METHODS: Forty-three subjects were grouped into (1) immunotherapy group: ragweed-allergic subjects on maintenance ragweed immunotherapy for at least 2 years (N = 16), (2) positive control group: ragweed-allergic subjects who had never received immunotherapy (n = 16), and (3) negative control group: ragweed-nonallergic subjects (N = 11). Ragweed specific skin tests and ragweed IgE levels were obtained prior to exposure. The study was done in a room where levels of 2,500 to 3,000 grains m3 of ragweed were maintained over three hours. Symptoms were recorded every 15 minutes. RESULTS: Nasal symptoms in the immunotherapy group were significantly less than in the positive control group after 45 minutes (P = .025). Significant differences were not observed for ocular symptoms. Combined nasal and ocular scores were 50% less in the immunotherapy group than in the positive control group by 75 minutes (P = .039). Ragweed-specific skin tests and IgE were significantly less in the immunotherapy group than in the positive control group. Rhinoconjunctivitis symptoms in the negative control group were absent throughout. CONCLUSIONS: Controlled ragweed pollen exposure in this setting demonstrated that ragweed immunotherapy significantly reduced symptoms of ragweed-allergic rhinitis but had no significant effect on ocular symptoms. This system presents opportunities for additional studies on immunotherapy for allergic respiratory conditions.

Adolescent↗
PubMed2006

[Quantitative analysis of donor chimerism in adoptive immunotherapy following allogeneic hematopoietic stem cell transplantation].

OBJECTIVE: To investigate the value of sequential and quantitative analysis of donor chimerism (DC) to predict the outcome of allogeneic hematopoietic stem cell transplantation (allo-HSCT), to determine the optimal time point of adoptive immunotherapy and to estimate the efficacy of adoptive immunotherapy. METHODS: Quantitative analysis of DC was performed with multiplex PCR amplification of short tandem repeats markers (STR-PCR) and capillary electrophoresis with fluorescence detection in 84 patients who received allo-HSCT. Sequential chimerism both prior to and following adoptive immunotherapy were evaluated in 16 patients. RESULTS: Increase of mixed chimerism and decrease of DC < 90% were found in 22 of the 84 patients. Six of the 22 patients who did not receive donor lymphocyte infusion (DLI) all died of relapse. Adoptive immunotherapy was used to treat the remaining 16 patients. Before the time of relapse or graft rejection, STR-PCR indicated decrease of DC in 12 of the 16 patients, with levels ranging from 24.8% - 86.2%. A response to immunotherapy was achieved in 11 of the 16 patients (68.8%). In these patients, the value of DC increased with conversion to a predominant donor profile (> or =90%). 6 of the 11 patients converted to stable full donor chimerism (FDC) and 5 of the 11 patients to transformed stable mixed chimerism (MC) shortly after immunotherapy. All these 11 patients who responded to immunotherapy developed graft versus host disease (GVHD). While in the patient without response, the level of DC decreased persistently or declined after a transient increase. Three patients without response received second DLI but still failed to response. CONCLUSION: The results demonstrate that sequential and quantitative monitoring of DC can identify the patients who have high risk of relapse or graft failure and can be used to guide adoptive immunotherapy at early stage to improve the response of immunotherapy in those patients who undergo cytogenetic or molecular relapse. Furthermore the serial and quantitative detection of DC has been shown to be a valuable tool to evaluate early the efficacy of treatment. As well, it can present a rational basis for treatment intensification in patients who did not respond to first-line adoptive immunotherapy treatment.

Adolescent↗
PubMed2005

Use of beta-blockers during immunotherapy for Hymenoptera venom allergy.

BACKGROUND: Beta-blockers may aggravate anaphylactic reactions and interfere with treatment. There is therefore concern about their use in patients who have a history of anaphylaxis or are on allergen immunotherapy. Immunotherapy is the best available treatment for prevention of life-threatening anaphylaxis to Hymenoptera stings, which is often observed in elderly patients who have cardiovascular disease and therefore are on beta-blocker treatment. OBJECTIVE: To analyze the risk of beta-blocker treatment during venom immunotherapy. METHODS: We screened all 1682 patients with Hymenoptera venom allergy seen during a period of 34 months for immunotherapy, cardiovascular disease, and treatment with beta-blockers. RESULTS: Of the 1389 patients in whom immunotherapy was recommended, 11.2% had cardiovascular disease, and 44 of these were on beta-blockers before immunotherapy. In 31 of those, the drug was replaced before starting treatment. In 3 with coronary heart disease and 1 with severe ventricular arrhythmia, the drug was continued throughout immunotherapy. In 9, it was reintroduced after reaching the maintenance dose. In an additional 12 patients, beta-blockers were newly started during immunotherapy. Of 25 patients on beta-blockers during immunotherapy, 3 (12%) developed allergic side effects, compared with 23 (16.7%) of 117 with cardiovascular disease but without beta-blockers. Systemic allergic symptoms after re-exposure by sting challenge or field sting were observed in 1 of 7 (14.3%) with and 4 of 29 (13.8%) without beta-blockade. No severe reactions to treatment or sting reexposure were observed in patients with beta-blockade. CONCLUSION: Combination of beta-blockers with venom immunotherapy may be indicated in heavily exposed patients with severe cardiovascular disease.

Adrenergic beta-Antagonists↗
PubMedDate not supplied

[Efficacy of immunotherapy in the treatment of asthma].

Specific immunotherapy consists of the administration of allergen extracts to patients with allergic disease to achieve clinical tolerance to the causative allergens. Currently, it is the only etiologic treatment for respiratory allergy. A World Health Organization opinion paper published in 1997 defines immunotherapy as "the only form of treatment able to modify the natural course of allergic diseases". In patients with allergic rhinitis, several studies suggest that immunotherapy can modify the natural history of respiratory allergy by preventing the development of asthma in children with this disease. Numerous studies demonstrate its efficacy in IgE-mediated asthma and particularly in mild-to-moderate asthma. When complete avoidance of the allergen cannot be achieved with measures that allow the patient to lead a normal life, pharmacological treatment can help to control symptoms, but symptoms immediately return when treatment is interrupted. However, asthma care can be improved by allergen-specific treatment; immunotherapy may shift the immune response from an allergic pattern toward a more protective response, producing persistent improvement with reduction of symptoms and the need for pharmacological treatment. Numerous comparative studies with specific immunotherapy vs. placebo or pharmacological treatment have demonstrated the efficacy of this treatment and its advantages in control of the disease. Specific immunotherapy induces favorable clinical, biological and functional modifications in the course of allergic asthma. Significant improvement in clinical manifestations has been demonstrated, even with levels of allergen exposure higher than those at the beginning of treatment. This improvement is associated with a reduced need for antiinflammatory and bronchodilator treatment. Moreover, specific bronchial reactivity shows a clear improvement with disappearance of delayed response and a clear increase in the threshold for immediate response to the allergen. Reduction in nonspecific bronchial hyperreactivity and improvement in exercise-induced asthma are also observed. Several studies recommend an optimal duration of specific immunotherapy for allergic asthma of between 3 and 5 years to achieve maximal therapeutic efficacy. A direct relationship between treatment duration and the persistence of its effects has been observed. Moreover, the treatment is more effective when started early. The possible adverse effects related to systemic reactions should be borne in mind. Although these effects are infrequent, maximal precautions should be taken when administering this treatment. Immunotherapy is contraindicated in cases of severe asthma, heart disease, autoimmune disease and associated severe neoplastic processes. However, all the beneficial effects of immunotherapy are conditioned by an accurate and early etiological diagnosis confirming the causative allergen. The availability of high-quality allergen extracts is essential to obtain the desired effect. Inappropriate patient selection for this treatment is the main cause of its failure. The integral treatment of allergic asthma includes environmental measures, patient education, pharmacological treatment and, whenever possible, immunotherapy.

Adult↗
PubMed2006

Effect of pretreatment with fexofenadine on the safety of immunotherapy in patients with allergic rhinitis.

BACKGROUND: Allergen-specific immunotherapy, although not a cure, remains the only treatment available that can alter the natural course of an allergic disease. However, the risk of allergen specific immunotherapy-related systemic reactions (SRs), reported to occur in approximately 1% to 14% of patients and which can range from mild to fatal in seriousness, represents a barrier to implementing this unique and effective treatment option. OBJECTIVE: To explore the possibility that pretreatment with the H1-antihistamine fexofenadine could prevent the occurrence of severe SRs induced by immunotherapy in Japanese patients with allergic rhinitis. METHODS: In this open-label, multicenter study, 134 patients receiving immunotherapy for allergic rhinitis were randomized 1:1 to a group receiving pretreatment with fexofenadine hydrochloride (60 mg) 2 hours before immunization injection (n = 67) or to a control group receiving no pretreatment (n = 67). Patients were further grouped into those who received cedar pollen immunotherapy and those who received dust mite immunotherapy. RESULTS: Pretreatment with fexofenadine 2 hours before immunotherapy significantly reduced the occurrence of severe SRs (P = .03), significantly increased the proportion of patients receiving cedar pollen immunotherapy who achieved the target maintenance dose (TMD) (P = .03), and significantly reduced the length of time to attain the TMD (P = .047 and P = .003 for patients receiving cedar pollen and dust mite immunotherapy, respectively). CONCLUSIONS: This study suggests a novel role for fexofenadine in enhancing the safety of immunotherapy and increasing the proportion of patients achieving the TMD.

Adult↗
PubMed1996

Ragweed immunotherapy in adult asthma.

BACKGROUND: Although allergen immunotherapy is effective for allergic rhinitis, its role in treating asthma is unclear. METHODS: We examined the efficacy of immunotherapy for asthma exacerbated by seasonal ragweed exposure. During an observation phase, adults with asthma who were sensitive to ragweed kept daily diaries and recorded peak expiratory flow rates between July and October. Those who reported seasonal asthma symptoms and medication use as well as decreased peak expiratory flow were randomly assigned to receive placebo or ragweed-extract immunotherapy in doses that increased weekly for an additional two years. RESULTS: During the observation phase, the mean (+/- SE) peak expiratory flow rate measured in the morning during the three weeks representing the height of the pollination season was 454 +/- 20 liters per minute in the immunotherapy group and 444 +/- 16 liters per minute in the placebo group. Of the 77 patients who began the treatment phase, 64 completed one year of the study treatment and 53 completed two years. During the two treatment years, the mean peak expiratory flow rate was higher in the immunotherapy group (489 +/- 16 liters per minute, vs. 453 +/- 17 in the placebo group [P = 0.06] during the first year, and 480 +/- 12 liters per minute, vs. 461 +/- 13 in the placebo group [P = 0.03] during the second). Medication use was higher in the immunotherapy group than in the placebo group during observation and lower during the first treatment year (P = 0.01) but did not differ in the two groups during the second year (P = 0.7). Asthma-symptom scores were similar in the two groups (P = 0.08 in year 1 and P = 0.3 in year 2). The immunotherapy group had reduced hay-fever symptoms, skin-test sensitivity to ragweed, and sensitivity to bronchial challenges and increased IgG antibodies to ragweed as compared with the placebo group; there was no longer a seasonal increase in IgE antibodies to ragweed allergen in the immunotherapy group after two years of treatment. Reduced medication costs were counterbalanced by the costs of immunotherapy. CONCLUSIONS: Although immunotherapy for adults with asthma exacerbated by seasonal ragweed exposure had positive effects on objective measures of asthma and allergy, the clinical effects were limited and many were not sustained for two years.

Adult↗
PubMed2001

Effect of allergen immunotherapy on soluble adhesion molecules.

UNLABELLED: The level of soluble adhesion molecules in the serum reflects the degree of systemic inflammation but the dynamics of these molecules in the pathogenesis of allergic diseases and their evolution during treatment, remains to be established. OBJECTIVE: To determine the evolution of the levels of soluble forms of serum intercellular adhesion molecule-1 (sICAM-1) and vascular cell adhesion molecule-1 (sVCAM-1) during immunotherapy to Dermatophagoides pteronyssinus in patients with allergic rhinitis and/or asthma. POPULATION: We included in this study 23 patients with perennial allergic rhinitis and/or asthma to Dermatophogoides pteronyssinus. 17 patients (6 males, 11 females, 13-48 years; mean: 27.2 years) were treated for one year with specific immunotherapy using standardized slow-release D. pteronyssinus extract (Lofarma, Milan, Italy). The other 6 patients (control group; 2 males, 4 females, 20-37 years; mean: 26.5 years) received only symptomatic treatment. METHODS: Serum sICAM-1 and sVCAM-1 were measured by ELISA method (R&D system). Blood samples were collected from each immunotherapy-treated patient at two timings: before immunotherapy (T0) and after one year of immunotherapy (T1). The two blood samples from each control patient (T0 and T1) were also collected one year apart. RESULTS: Before Immunotherapy (T0), the mean serum level of sICAM-1 was 336.0 ng/ml. After one year of immunotherapy (T1) it decreased to 325.2 ng/ml but this difference was not statistically significant. Mean serum level of sVCAM-1 was 655.5 ng/ml before immunotherapy (T0), decreasing significantly (p < 0.05) to 568.2 ng/ml (T1). In the control group both sICAM-1 and sVCAM-1 had no significant changes (sICAM-1: 363.1 ng/ml (T0) and 374.7 ng/ml (T1); sVCAM-1: 611.5 ng/ml (T0) and 649.8 ng/ml (T1). CONCLUSIONS: These results suggest that specific immunotherapy with D. pteronyssinus induces a decrease in serum sVCAM-1 but not in sICAM-1 levels. The decreased expression of sVCAM-1 after immunotherapy is probably related to a decrease in the inflammatory reactions.

Adolescent↗
PubMed1982

BCG immunotherapy of lung cancer in a district oncology dispensary. I. Study of 860 patients with histologic diagnosis.

The investigation refers to lung cancer patients registered in an oncology dispensary from 1965 to 1975. The conventional treatment (surgery, radiotherapy and chemotherapy) has covered 35.9% of all patients, whereas immunotherapy with BCG or with its soluble fraction has been applied in 46.2% of them. Immunotherapy has mainly been applied to epidermoid carcinoma and large-cell carcinoma. Comparing the survival of immunotherapy treated with non-immunotherapy treated patients it was found that in Stage I-II group the difference in favor of immunotherapy was significant in the second year of observation and in Stage III group a significant difference was found in all observation periods (1-5 years). In Stage I-II the 5-year survival rate of immunotherapy treated patients (13.2%) was similar to the survival rate of operated patients (13.7%). Immunotherapy in large cell carcinoma showed significantly better results than immunotherapy in epidermoid carcinoma. Immunotherapy with BCG and F70 was applied as an independent treatment of lung cancer. When applied to patients primarily operated, radiation or chemotherapy treated, the survival was significantly higher than the survival of patients submitted to conventional treatment or to immunotherapy separately.

Adenocarcinoma↗
PubMed1997

Adjuvant immunotherapy for patients with melanoma: are patients with melanoma of the head and neck candidates for this therapy?

BACKGROUND: Although a wealth of information is available on adjuvant immunotherapy for melanoma, little is known about adjuvant immunotherapy for head and neck melanoma. Interestingly, a few immunotherapy clinical trials report the observation of clinical responses in a subset of patients with head and neck melanoma. METHOD: An up-to-date literature search was performed to identify the current information on adjuvant immunotherapy for patients with melanoma, including head and neck melanoma. Moreover, a retrospective analysis of a subset of primary head and neck melanoma was performed using data from a phase III, randomized, double-blind, multi-institutinal, vaccinia melanoma oncolysate adjuvant immunotherapy trial that was performed in our laboratory for patients with stage III (AJCC) melanoma. RESULTS: In a passive immunotherapy trial with an antibody to melanoma ganglioside antigen GM2, a complete regression was observed in one patient with lesions of the right cheek. In three active specific immunotherapy trials, including our phase III trial, a subset of patients with head and neck primary melanoma showed a longer disease-free and overall survival with immunotherapy. Moreover, these clinical responses were correlated to the induction of immune response, delayed-type hypersensitivity response and melanoma-specific antibody response. CONCLUSIONS: The above results therefore suggest that patients with head and neck melanoma clinically respond to immunotherapy. However, these results need to be confirmed in a prospectively randomized trial for patients with head and neck melanoma.

Cancer Vaccines↗
PubMed1993

Systemic chemotherapy combined with local adoptive immunotherapy cures rats bearing 9L gliosarcoma.

Survival of Fischer rats bearing 9L gliosarcoma in the brain was measured to determine the efficacy of 1) systemically administered chemotherapy with local adoptive immunotherapy (chemo-adoptive immunotherapy) or 2) systemically administered chemo-immunotherapy. Winn assays, where tumor instillation coincided with the start of treatment, and one-week established tumor assays were conducted. Survival of chemo-adoptive immunotherapy treated groups given intraperitoneal cyclophosphamide and intracranial lymphokine activated killer cells and recombinant Interleukin-2 was significantly extended when compared to sham treated control groups, to groups given chemotherapy with intraperitoneal cyclophosphamide, and to groups treated by local adoptive immunotherapy with intracranial lymphokine activated killer cells and Interleukin-2. The killer cells were generated from spleens of donor rats that either had or had not been given cyclophosphamide 24 h earlier. Long-term survivors (9/39), sacrificed at day 70, were obtained only in the chemo-adoptive immunotherapy treated groups; 7/39 had no histologic evidence of tumor and had focal sterile abscesses at the site of killer cell instillation. Average group weight plotted over time showed that there was acceptable toxicity with chemo-adoptive immunotherapy; the toxicity was identical to that obtained with systemic cyclophosphamide treatment. In contrast, survival of chemo-immunotherapy treated groups given systemic cyclophosphamide and Interleukin-2 was not significantly extended from groups which were sham treated or treated only with systemic Interleukin-2. Rapid decline of average group weight plotted over time and early deaths following chemo-immunotherapy treatment indicated that the regimen was toxic. The effect of cyclophosphamide administration on the splenocytes of donor rats and the LAK cells generated from them was determined by in vitro studies analyzing cell number, viability, phenotypic expression and cytotoxicity against 9L tumor. In the treatment of this intracranial neoplasm, the beneficial effects of cyclophosphamide were determined to occur in situ in the tumor-bearing host. No benefit resulted from cyclophosphamide treatment of donor rats that supplied splenocytes for LAK cell production.

Animals↗
PubMed1976

Lung cancer: An immunologic viewpoint and the prospects for immunotherapy.

The size of the lung cancer problem and the dismal results of conventional therapy justify close attention to the possibilities of immunotherapy. Lung cancer patients, like other tumor patients, are often relatively immunosuppressed although an immune response directed against autochthonous tumor cells can usually be demonstrated. All conventional forms of therapy, surgery, chemotherapy, and particularly radiation therapy, are further immunosuppressive, which, there is reason to believe, jeopardizes a successful outcome. Immunotherapy seeks to counteract this either by nonspecfic immunoenhancement or by enhancing reactivity to tumor specific antigens. The results of immunotherapy trials in lung cancer patients suggest that survival can be prolonged and survivorship increased by immunotherapy, although the benefit is inconclusuve at present. Optimal conditions for immunotherapy, as presently understood, are outlined. Practical questions about the optimal use of current immunotherapy regimens need to be answered, but a more aggressive approach to lung cancer therapy when combined with immunotherapy seems justified. Im pariicular, the criteria for operability will need to be redefined, particularly as regards oat cell cancer and large tumors which cannot be completely resected but in which "debulking" may contribute to the success of subsequent radiation and immunotherapy. Possible future immunotherapy regimens applicable to lung cancer are proposed, with the reservation that their success is likely to be directly related to their practicability.

Chicago↗
PubMed1996

Mite-specific induction of interleukin-2 receptor on T lymphocytes from children with mite-sensitive asthma: modified immune response with immunotherapy.

BACKGROUND: The efficacy of immunotherapy is still controversial. To elucidate the mechanisms of immunotherapy, we studied mite-specific induction of IL-2 receptor (IL-2R) expression on T lymphocytes from children with mite-sensitive asthma. METHODS: Peripheral blood mononuclear cells were obtained from 28 children with mite-sensitive asthma: 13 had never received house dust immunotherapy (nonimmunotherapy group), 15 had been receiving house dust immunotherapy at the time of the study (immunotherapy group). After a 6-day culture with or without Dermatophagoides farinae (Df) antigen, the expression of IL-2Rp55 (CD25) and p75 on CD4+ or CD8+ T lymphocytes was measured by flow cytometry. RESULTS: The nonimmunotherapy group showed significant Df-specific CD25 induction on CD4+ T lymphocytes (delta CD4+ CD25+) but little induction on CD8+ T lymphocytes (delta CD8+ CD25+). delta CD4+ CD25+ was correlated with the severity of the disease. In the immunotherapy group delta CD8+ CD25+ was significantly higher than in the nonimmunotherapy group or in normal subjects and correlated with Df-specific IgG4 and cumulative doses of house dust extract, whereas delta CD4+ CD25+ was similar in the nonimmunotherapy and the immunotherapy groups. IL-2Rp75 was not induced either on CD4+ or CD8+ T lymphocytes. CONCLUSIONS: Our data suggest that house dust immunotherapy may have induced Df-specific CD8+ T lymphocytes in patients with mite-sensitive asthma and that the efficacy of immunotherapy may be attributed to the generation of Df-specific CD8+ T lymphocytes.

Adolescent↗