Immunotherapy Protocols Research Articles

Safety of 1 mcg/mL as the starting dose in cluster protocol for hymenoptera immunotherapy.

Hymenoptera venom allergy is a potentially severe allergic reaction in the general population. The only preventative approach in these cases is venom immunotherapy (VIT), which follows different protocols. The recommended initial dose is 0.001-0.1 mcg of venom extract. However, few reports have declared the safety of 1 mcg venom as the starting dose. The study was conducted on Iranian patients with a history of anaphylaxis to venom. Skin tests confirmed hypersensitivity to honeybee, yellow jacket, and/or paper wasp from subfamily Polistes using Apis melifera, Vespula spp, and Polistes spp venom extracts, respectively. Subsequently, the patients were treated with the cluster protocol. Twenty-two patients (17 males and 5 females, aged 28.3±11.8 years) were enrolled in the study. Skin prick tests and intradermal tests showed positive results for yellow jacket in 17 (77.3%) and 21 (95.4%) patients, honeybee in 14 (63.6%) and 17 (77.3%) patients, and wasp in 14 (63.6%) and 17 (77.3%) patients, respectively. Upon administering the initial dose of 1 mcg/mL, 40.9% (9 cases) of patients presented mild local reactions, including 7 with yellow jacket allergy, 5 with honeybee allergy, and 3 with wasp allergy. One patient with yellow jacket allergy had a mild systemic reaction. Patients with a positive skin test for wasp had significantly lower rate of reactions after the first dose of venom (p=0.026). Throughout the entire build-up phase, more than 90% (20 of 22) of patients experienced mild local reactions, followed by large local reactions (3 cases, 13.6%), mild systemic reactions (1 case at 1 mcg/mL dose), and moderate-to-severe systemic reactions (3 cases, 13.6%). Large local and moderate-to-severe systemic reactions were detected after injecting 50 mcg (each one case) and 100 mcg (each 2 cases) of venom extracts. This study recommends 1 mcg/mL of the venom extract as a safe starting dose for VIT. This accelerated protocol could successfully reduce the time and costs of therapy for patients undergoing out-patient cluster VIT.

A hypoxia-activated and microenvironment-remodeling nanoplatform for multifunctional imaging and potentiated immunotherapy of cancer

Activatable theranostic systems combining precise diagnosis and robust immune activation have significant potential in cancer treatment. Herein, we develop a versatile nanoplatform integrating hypoxia-activatable molecular imaging with effective photoimmunotherapy for cancer treatment. Our molecular probe features turn-on near-infrared-II (NIR-II) fluorescence and photoacoustic signals in hypoxic tumor environments. It also induces hypoxia-triggered photodynamic and photothermal effects, promoting immunogenic cell death and activating the STING pathway, engaging both innate and adaptive immunity. The molecular probe is formulated with a vascular disrupting agent to amplify the hypoxia-responsive phototheranostic properties, on which M1-like macrophage membrane is camouflaged to shield against premature release while conferring cancer-targeting affinity. The activatable NIR-II fluorescence and photoacoustic imaging enable precise tumor delineation, while the enhanced phototherapy activates tumor-specific cytotoxic T cells, impeding both primary and distant tumor progression and providing protective immunity against rechallenge in 4T1 tumor-bearing female mice. This work advances activatable theranostic protocols for image-guided immunotherapy.

Abstract IA025: Targeting the gut microbiome for cancer immunotherapy

Abstract Growing evidence suggests that the gut microbiota modulates the efficacy and toxicity of cancer therapy, most notably immunotherapy and its immune-related adverse effects. The impaired response to immunotherapy in patients treated with antibiotics supports this role of the microbiota. Until recently, results pertaining to the identification of the microbial species responsible for these effects were incongruent, and relatively few studies analyzed the underlying mechanisms. Gut microbial communities (microbiotypes) with non-uniform geographic distribution were associated with favorable and unfavorable outcomes, contributing to discrepancies between cohorts Now, a better understanding of the taxonomy of the species involved and of their mechanisms of action has been achieved. Defined bacterial species have been shown to promote a response to immune checkpoint inhibitors through the production of different products or metabolites, although a suppressive effect of Gram(-) bacteria may be dominant in some unresponsive patients. Machine learning approaches trained on patients’ microbiota composition can predict the ability of patients to respond to immunotherapy with some accuracy. Thus, the interest in modulating the microbiota composition to improve patients’ responsiveness to therapy has been mounting. Our data of a fecal microbiota transfer clinical trial in anti-PD1 refractory melanoma patients has provided clinical proof of concept of the possibility to target the gut microbiota composition in cancer therapy. Also, both in clinical studies and in experimental animals, diets rich in fibers improve the response to immunotherapy by modifying the gut microbiome suggesting the possibility of dietary approaches to target the microbiota composition in cancer therapy. However, while many early clinical studies have analyzed the association of the microbiota composition with the response to anti-PD-1 in cancer patients, emerging evidence suggests that the association may be context dependent and different types of mono or combination immunotherapies may be differentially regulated by the microbiota, Thus, a more personalized approach depending original gut microbiota composition of the patients and the type of immunotherapy protocol selected may be necessary for optimal clinical results. Citation Format: Giorgio Trinchieri. Targeting the gut microbiome for cancer immunotherapy [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor-body Interactions: The Roles of Micro- and Macroenvironment in Cancer; 2024 Nov 17-20; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(22_Suppl):Abstract nr IA025.

Evaluation of the protocol for rush subcutaneous immunotherapy with birch pollen extract.

We previously reported the effectiveness of rush subcutaneous immunotherapy with birch pollen extract (Birch rSCIT) for pollen-food allergy syndrome (PFAS) and the high rate of systemic reactions (SR) during the rapid escalation phase. In this study, we examined whether modifying the dose escalation protocol of Birch rSCIT would reduce SR and maintain therapeutic effects. Birch rSCIT was introduced in 20 patients with PFAS who experienced systemic symptoms upon ingestion of soybeans. Birch rSCIT was implemented using 3 protocols: 2 protocols (nonstep-up group) increased the target dose to more than 1:2 × 102 (w/v) in 0.05 mL, while 1 protocol (step-up group) increased the target dose to 1:2 × 103 (w/v) in 0.3 mL, and then increased to 1:2 × 102 (w/v) in 0.05 mL using the conventional method in the following week. In the nonstep-up group, 4 out of 5 patients (80%), and in the step-up group, 2 out of 15 patients (13.3%) developed SR during rapid escalation. During the rapid escalation phase, the step-up group had significantly fewer SR than the nonstep-up group (P = 0.014). The median ingestible dose of soy milk in the oral food challenge was 3.5 mL before the treatment and increased significantly to 200 mL 1 year after initiating Birch SCIT (P < 0.01). We confirmed that reducing the target antigen dose in Birch rSCIT improved safety and maintained the therapeutic effect for soybean allergy with PFAS.

EP.08A.02 Adherence to Adjuvant Immunotherapy and Target Therapy Protocols Inpatients with Resected NSCLC: A Meta Analysis

EP.08A.02 Adherence to Adjuvant Immunotherapy and Target Therapy Protocols Inpatients with Resected NSCLC: A Meta Analysis

Venom immunotherapy in clinical practice: comparison of two ultra-rush protocols.

Background. Ultra-rush venom immunotherapy protocols have shown to be a safe and effective approach to prevent the occurrence of systemic reactions after hymenoptera stings. The aim was to describe our experience with two ultra-rush protocols - a five-step with 1 µg starting dose and a six-step with 0.1 µg starting dose, as well as to compare their safety profile. Methods. This is a retrospective study of all the patients who underwent VIT with honey bee or wasp venom between January 2008 and December 2021, in our department. Results. A total of 110 patients was included, with 109 patients (99%) completing the protocol. A total of 63 (57%) patients had no local or systemic reactions. Most systemic reactions occurred with 20 µg or higher doses (24, 83%). There were no documented grade IV systemic reactions (Mueller grading). No differences were found in local or systemic reactions regarding sex, atopy, β-blocker medication, the severity of the index reaction, ID test positivity, levels of total IgE, specific IgE and tryptase (all p > 0.05). Younger age, treatment with bee VIT or being a beekeeper were associated with more systemic reactions (p = 0.035, 0.006 and 0.047, respectively). No statistical differences in the number of local and systemic reactions were found when comparing both protocols (p = 1.000). Conclusions. Ultra-rush protocols are safe and effective, but systemic reactions are to be expected, especially with honeybee. Our data supports that ACE inhibitors do not compromise safety. Beginning with 1 µg is safe and can save time and resources.

Immunotherapy for children with malignant brain tumors

The incidence of high-grade malignant gliomas (MG) ranges from 35 to 46% of all central nervous system tumors. Despite combined therapy including surgery, radiation treatment and chemotherapy, overall five-year survival does not exceed 10%. The advent of novel immunotherapeutic strategies has promoted a renewed hopes for the treatment of MG. The aim of the present study was to improve the survival rates of glioma patients. Our study included 5 pediatric patients at the median age of 7.6 years (2-16). Three pts had anaplastic astrocytoma (AA) (1st relapse, 1 pt; 2nd relapse, in 2 pts), One patient was diagnosed with glioblastoma multiforme (GBM) (3rd recurrence), and 1 child had diffuse brainstem glioma (BSG). The median time to the first relapse was 12 months (4 to 16), the second relapse occurred at a median of 5 months (1 to 8). The protocol of immunotherapy included combined administration of autologous dendritic cell-based vaccine (DV) and repeated intrathecal/intraventricular injections of donor allogeneic immunocompetent cells (alloIC) for at least 2 years. Two of 3 pts with AA experienced a progression-free interval of 67 and 71 months. One patient with 3rd GBM relapse is alive without any treatment for 13.3 years after starting the immunotherapy. The median time of follow-up was 67 months, with the 2-year overall survival rate of 58%. Two pts died from the disease progression within 6 and 7 months from the beginning of immunotherapy. Over the period of treatment, the patients received a median of 20 alloIC injections (8 to 60), and 18 DV administrations (8 to 44). No serious side-effects were observed. Immunotherapy could be an promising option for treating patients with high-grade malignant gliomas refractory to conventional therapy and, therefore, deserves further investigations.

Disease-burden-adapted immunotherapy protocol for primary refractory or high-risk relapsed pediatric acute lymphoblastic leukemia.

Disease-burden-adapted immunotherapy protocol for primary refractory or high-risk relapsed pediatric acute lymphoblastic leukemia.

A retrospective study of a novel 3-session rush venom immunotherapy protocol

BackgroundVenom immunotherapy (VIT) is an effective treatment for life-threatening stinging-insect hypersensitivity. Rush VIT protocols allow patients to reach maintenance dosing faster, thus conferring protection sooner. The published protocols vary in dosing regimens, monitoring parameters, and safety profiles. ObjectiveTo describe a novel 3-session outpatient rush VIT protocol with full therapeutic dosing achieved at the end of session 3. MethodsWe conducted a retrospective chart review of adult patients treated with rush VIT in an outpatient university allergy/immunology clinic. Demographic and clinical data, including the type of sting reaction, the number of venom allergens, and any systemic reactions (SRs) during VIT, were analyzed. ResultsOver a 14-year period, 55 patients (28 females and 27 males) with a median age of 47 years underwent our VIT protocol. A total of 46 patients (84%) tolerated the procedure without SR, and 53 (96%) attained full maintenance dosing. All reactions during rush were Brown anaphylaxis criteria grade 1 or 2. Although the most common venom allergy was yellow jacket, most patients had multiple venom allergies and received therapy with more than 1 venom. Furthermore, 10 patients were re-stung while on maintenance with only 1 patient having a mild SR. ConclusionOur 3-session outpatient rush VIT protocol is effective and safe. Most patients had no SR and attained maintenance dosing. Compared with other 3-session rush protocols, our protocol requires non-invasive monitoring, and patients achieved monthly maintenance dosing immediately on completion.

Emerging Strategies in Thyroid Cancer Immunotherapy: A Comprehensive Systematic Review and Meta-Analysis of Clinical Outcomes

Introduction: The most prevalent endocrine cancer is thyroid cancer (TC), which has a low death rate despite a rising frequency. In order to assess the clinical results of novel immunotherapeutic approaches in TC, this systematic review and meta-analysis will concentrate on treatment-related adverse events (AEs), overall response rate (ORR), progression-free survival (PFS), and overall survival (OS). Methods: A thorough search was done on PubMed, Embase, and ClinicalTrials.gov, covering research published between January 2018 and December 2023. The inclusion criteria were satisfied by 14 research, including a range of TC subtypes and study methodologies.Results: The effectiveness of immunotherapy varied throughout TC subtypes. In advanced TC with PD-L1 positivity, pembrolizumab showed a 9% ORR and a 7-month PFS. In advanced/metastatic TC, camrelizumab + famitinib demonstrated ORRs of 33.3%-62.5% and 8.4-month PFS. Patients who tested positive for PD-L1 had greater responses to spartalizumab (19% ORR) in ATC. Combination treatments, such as pembrolizumab and lenvatinib, demonstrated encouraging outcomes in ATC and poorly differentiated thyroid cancer (PDTC), with 34.3% ORRs and a significant increase in PFS. With the fixed-effects model, the pooled ORR was 40.8% (95% CI, 37.2%-44.5%), and with the random-effects model, it was 33.4% (95% CI, 20.8%-48.9%). Considerable heterogeneity (I2 = 94.4%, p &lt; 0.01) demonstrated varying treatment outcomes across several immunotherapy protocols. Conclusion: Immunotherapy has promise in the treatment of advanced tuberculosis, especially aggressive forms such as ATC, especially when used in combination regimens. Subsequent investigations have to concentrate on refining combination tactics and finding biomarkers for patient selection.

A novel dose-adjustment protocol for interrupted subcutaneous immunotherapy in children with allergic rhinitis.

Aim: To assess the effectiveness and safety of a new protocol for adjusting doses during interrupted subcutaneous immunotherapy maintenance, exceeding an 8-week interval, with mite allergen injections in children with allergic rhinitis.Patients & methods: 194children with allergic rhinitis who underwent subcutaneous immunotherapy and experienced interruptions lasting more than 8 weeks during maintenance were enrolled. Following the adoption of a novel dose-adjustment protocol, a real-world study was conducted.Results: After 3years of subcutaneous immunotherapy, the novel group exhibited a significant reduction in allergy symptoms compared with baseline. Systemic reactions related to the novel protocol did not significantly increase.Conclusion: The novel protocol was deemed safe and effective, offering advantages of time savings and reduced burdens.

Biomaterials-Boosted Immunotherapy for Osteosarcoma.

Osteosarcoma (OS) is a primary malignant bone tumor that emanates from mesenchymal cells, commonly found in the epiphyseal end of long bones. The highly recurrent and metastatic nature of OS poses significant challenges to the efficacy of treatment and negatively affects patient prognosis. Currently, available clinical treatment strategies primarily focus on maximizing tumor resection and reducing localized symptoms rather than the complete eradication of malignant tumor cells to achieve ideal outcomes. The biomaterials-boosted immunotherapy for OS is characterized by high effectiveness and a favorable safety profile. This therapeutic approach manipulates the tumor microenvironments at the cellular and molecular levels to impede tumor progression. This review delves into the mechanisms underlying the treatment of OS, emphasizing biomaterials-enhanced tumor immunity. Moreover, it summarizes the immune cell phenotype and tumor microenvironment regulation, along with the ability of immune checkpoint blockade to activate the autoimmune system. Gaining a profound comprehension of biomaterials-boosted OS immunotherapy is imperative to explore more efficacious immunotherapy protocols and treatment options in this setting.

Diagnosis and treatment of Hymenoptera venom allergy in adults: A single-center experience in Lithuania

BackgroundVenom-specific immunotherapy (VIT) is a major treatment for patients allergic to Hymenoptera venom. Thus, correct diagnosis of sensitization, identification of the risk factors, and choice of venom for the treatment are the key issues. ObjectiveWe aimed to describe diagnostic and treatment experience data of VIT performed in a single center in Lithuania. MethodsIn this retrospective study, we analyzed 9 years of clinical data (severity of the allergic reaction, recognition of the culprit insects, diagnostics, VIT protocol safety and efficacy, sting challenge outcomes) of patients treated with cluster VIT. Sting challenge helped to reveal the influence of venom preparation quality and to adjust the dosage of venom. ResultsData from 83 patients were analyzed. Double sensitization confirmed by component diagnosis was found in 39.4% (13/33), and double immunotherapy was initiated in 9.1% (n = 3/33). The cluster immunotherapy protocol was used in 81 patients. Systemic reactions occurred in 7.4% (n = 6/81) patients during the build-up phase. VIT failure was related to bee venom immunotherapy and systemic reactions during a build-up phase. The efficacy in the short term of our approach to cluster VIT was confirmed by the sting challenge in 97% (42/43). Nine patients (10.8%, n = 9/83) voluntarily stopped the treatment due to a lack of motivation. ConclusionOur protocol regarding the investigation and treatment of patients allergic to Hymenoptera venom has been safe and effective. Patient's motivation to continue VIT is one of the concerns, but the biggest challenge is the patients with bee venom allergy and repeated systemic reactions during VIT.

Validation of the NUT CRACKER Diagnostic Algorithm and Prediction for Cashew and Pistachio Co-Allergy

BackgroundDue to the high cross sensitization among tree nuts, the NUT CRACKER study proposed a diagnostic algorithm to minimize the number of required oral food challenges (OFC). ObjectiveThe objective of this study was to validate the algorithm for cashew and pistachio allergy and determine markers for allergic severity. MethodsPatients (n=125) aged 7.9 (5.9-11.2) years (median (IQR)) with suspected tree nut allergy were evaluated prospectively with decision tree points based on skin prick test (SPT), basophil activation test (BAT) and knowledge of the coincidence of allergies. Validation of allergic status was determined by OFC. Markers of clinical severity were evaluated using the combined original and prospective cohort (n=187) in relationship to SPT, BAT and Ana o 3-sIgE. ResultsReactivity to cashew in SPT, BAT and Ana o 3-sIgE and the incidence of abdominal pain upon challenge were significantly higher in dual-allergic cashew/pistachio patients (n=82) vs single cashew allergy (n=18) (p=0.001). All three diagnostic tests showed significant inverse correlation with log10 reaction doses for positive cashew OFC. The algorithm reduced overall the total number of OFCs by 72.0% with a PPV and NPV of 93.0% and 99.0%, respectively. Cashew false positives were observed primarily in hazelnut allergic patients (p=0.026). In this population, Ana o 3-sIgE could diagnose cashew allergy with a sensitivity over 90%, and a specificity over 95%. ConclusionThe NUT CRACKER diagnostic algorithm was validated and reduced the number of diagnostic OFCs required. Markers for severity phenotypes may guide oral immunotherapy protocols, improving the risk/benefit ratio for patients.

Neoadjuvant Immune Checkpoint Inhibitors in hepatocellular carcinoma: a meta-analysis and systematic review.

Neoadjuvant immunotherapy has demonstrated beneficial outcomes in various cancer types; however, standardized protocols for neoadjuvant immunotherapy in hepatocellular carcinoma (HCC) are currently lacking. This systematic review and meta-analysis aims to investigate the reliability of neoadjuvant immunotherapy's efficacy and safety in the context of HCC. A systematic search was conducted across PubMed (MEDLINE), EMBASE, the Web of Science, the Cochrane Library, and conference proceedings to identify clinical trials involving resectable HCC and neoadjuvant immunotherapy. Single-arm meta-analyses were employed to compute odds ratios and 95% confidence intervals (CIs). Heterogeneity analysis, data quality assessment, and subgroup analyses based on the type of immunotherapy drugs and combination therapies were performed. This meta-analysis is registered in PROSPERO (identifier CRD42023474276). This meta-analysis included 255 patients from 11 studies. Among resectable HCC patients, neoadjuvant immunotherapy exhibited an overall major pathological response (MPR) rate of 0.47 (95% CI 0.31-0.70) and a pathological complete response (pCR) rate of 0.22 (95% CI 0.14-0.36). The overall objective response rate (ORR) was 0.37 (95% CI 0.20-0.69), with a grade 3-4 treatment-related adverse event (TRAE) incidence rate of 0.35 (95% CI 0.24-0.51). Furthermore, the combined surgical resection rate was 3.08 (95% CI 1.66-5.72). Subgroup analysis shows no significant differences in the efficacy and safety of different single-agent immunotherapies; the efficacy of dual ICIs (Immune Checkpoint Inhibitors) combination therapy is superior to targeted combined immunotherapy and monotherapy, while the reverse is observed in terms of safety. Neoadjuvant immunotherapy presents beneficial outcomes in the treatment of resectable HCC. However, large-scale, high-quality experiments are warranted in the future to provide robust data support.

The Three-dimensional Environment of Type Ⅰ Collagen Gels With Varying Stiffness Modulates the Immunological Functions of NK Cells

To construct type Ⅰ collagen gels with different stiffness and to investigate the effects of three-dimensional (3D) culture environments of the gels on the morphology, free migration ability, and cell killing function of natural killer (NK) cells. Type Ⅰ collagen was isolated from the tails of Sprague Dawley (SD) rats and collagen gels with different levels of stiffnesses were prepared accordingly. The microstructure of the collagen gels was observed by laser confocal microscopy. The stiffness of the collagen gels was assessed by measuring the plateau modulus with a rheometer. NK-92MI cells were cultured in collagen gels with different levels of stiffness. The morphology of NK-92MI cells was observed by inverted microscope. High content imaging system was used to record the free migration process of NK-92MI cells and analyze the migration speed and distance. NK-92MI cells were cultured with type Ⅰ collagen gels with different levels of stiffness for 24 h and 48 h and, then, co-cultured with human colorectal DLD-1, a human adenocarcinoma epithelial cell line. CCK8 assay was performed to determine the proliferation rate of DLD-1 cells and analyze the cell killing ability of NK-92MI cells. Low-stiffness type Ⅰ collagen gel and high-stiffness type Ⅰ collagen gel with the respective stiffness of (10.970±2.10) Pa and (114.50±3.40) Pa were successfully prepared. Compared with those cultured with the low-stiffness type Ⅰ collagen gel, the NK-92MI cells in the high-stiffness type Ⅰ collagen gel showed a more elongated shape (P<0.05), the mean area of the cells was reduced ([69.88±26.97] μm2 vs. [46.59±21.62] μm2, P<0.05), the roundness of the cells decreased (0.82±0.12 vs. 0.78±0.18, P<0.05), cell migration speed decreased ([2.50±0.91] μm/min vs. [1.70±0.72] μm/min, P<0.001) and the migration distance was shortened ([147.10±53.74] μm vs. [98.03± 40.95] μm, P<0.0001), with all the differences being statistically significant. Compared with those cultured with the low-stiffness type Ⅰ collagen gel, NK-92MI cells cultured with high-stiffness type Ⅰ collagen gel for 24 h could promote DLD-1 cell proliferation, with the proliferation rate being (46.39±12.79)% vs. (65.87±4.45)% (P<0.05) and reduce the cell killing ability. Comparison of the cells cultured for 48 h led to similar results, with the proliferation rates being (31.36±2.88)% vs. (74.57±2.16)% (P<0.05), and the differences were all statistically significant. The 3D culture environment of type Ⅰ collagen gels with different levels of stiffness alters the morphology, migration ability, and killing function of NK-92MI cells. This study provides the research basis for exploring and understanding the mechanisms by which the biomechanical microenvironment affects the immune response of NK cells, as well as laying the theoretical foundation for optimizing immunotherapy protocols.

Selective cytotoxicity and anticancer activity: ROS-induced cell death facilitated by metal complex

Hepatocellular carcinoma (HCC) recurrence rate consists of 10%-20% and remains the leading cause of cancer-related death. We have successfully designed the protocol for adoptive immunotherapy to liver cirrhotic patients with HCC. In our study we have shown that activated lymphocytes, containing much of immune cells of innate immunity, from healthy volunteers, have a vigorous anticancer effect. However, the volume and viability for the treatment with activated lymphocytes might lead to limited effects. We aimed to develop a new therapeutic approach for the efficient expansion of such innate components of cellular immunity in combination with metal complex. Human lymphocytes were cultured for 7 days by appropriate protocol with cytokines. The phenotype and characterization of activated lymphocytes were identified by flow cytometric analysis and the cytotoxicity against tumor was determined. After being cultured for 7 days the proportion of cell fractions in the expanded activated lymphocytes varied among individuals. The average proportion of immune cells of innate immunity which were activated were in a high level. The addition of metal complex exhibits enhanced expression of surface receptors and intracellular cytokines which involved in antitumor process. Activated lymphocytes in combination with metal complex showed vigorous anticancer ability in vitro, of HepG2, an HCC cell line. These findings suggest that adoptive immunotherapy using activated lymphocytes might be a promising approach for inducing innate immunity to decrease the incidence of cancer recurrence and repeatedly applied in the clinical setting.

Characteristics of adverse reactions due to subcutaneous allergen immunotherapy applied between 2011-2021: Single center experience.

The aim of this study was to elucidate the incidence of local, large local and systemic reactions after subcutaneus immunotherapy (SCIT) injections in our clinic and to determine the characteristic features of these adverse reactions. A total of 6000 SCIT injections administered to 163 patients between January 2011 and December 2021 were retrospectively evaluated. The study population consisted of patients with allergic rhinoconjunctivitis who underwent SCIT due to pollen, house dust mite or cat allergy, or patients who underwent SCIT due to venom allergy. Demographic characteristics of the patients, diagnoses, allergen sensitivities, immunotherapy protocol applied, adverse reactions, and the characteristics of these reactions were recorded. Totally, 163 patients with a mean age of 36.8 ± 12.7 years were enrolled in this research. Sex distribution was as follows: 55.2% (n= 90) were females. During the study, 218 allergic reactions were detected in 83 patients. The incidence of adverse reactions per injection was 3.6%. The probability of developing an adverse reaction in a patient during the entire subcutaneous immunotherapy was 53.9%. Of the adverse reactions that developed, 94 (43.1%, n= 47) were observed locally while 56 (25.7%, n= 40) were large local reactions, and 68 (31.2%, n= 30) were systemic. Incidence of adverse reactions per injection were 1.5%, 0.9%, and 1.1% for local reaction, large local reaction, and systemic reaction, respectively. The results of this analysis elaborated that subcutaneous immunotherapy is a safe and tolerable treatment modality. However, before initiating treatment, the benefits and risks should be evaluated. The risk of systemic reactions is quite low, but fatal anaphylaxis can occur, so physicians need to be aware of the potential risks.

Mathematical modeling of tumor-immune system dynamics subject to dendritic cells immunotherapy: a brief review

Currently, there is a promising therapy to treat cancer that uses dendritic cell infusions. Dendritic cells play a crucial role in the initiation, programming, and regulation of the specific immune response, for this reason they are considered the best antigen-presenting cells. The objective of using them in immunotherapy is to induce a specific immune response of T cells towards cancer cells. This article provides a brief review of three mathematical models of the tumor-immune system interaction subject to dendritic cell immunotherapy. It is important to point out that analyzing mathematical models is a crucial stage in the design of control laws for establishing optimal administration protocols for dendritic cell immunotherapy.

FRI233 Adrenal Insufficiency Due To An Unusual Culprit

Abstract Disclosure: S. Decamps: None. K.T. Yeung: None. K. McCowen: None. Background: Chronic exogenous use of glucocorticoids is the most common cause of reversible secondary adrenal insufficiency (AI). There is a significant risk of cortisol deficiency if the medication is abruptly discontinued. Chronic glucocorticoid therapy may cause hypothalamic-pituitary-adrenal (HPA) axis suppression, resulting in low ACTH, atrophy of the adrenal zona fasciculata and decreased cortisol production. Immunotherapy rarely causes reversible central AI, usually permanent. We present a case of an immunotherapy-receiving patient who presented with biochemical evidence of adrenal insufficiency after using an oral solution (swish and spit) of dexamethasone as prophylaxis for mucositis. Patient Summary: A 52-year-old woman with stage IIb triple negative breast cancer receiving neoadjuvant Datopotamab, Dertuxtecan and Durvalumab was evaluated for adrenal insufficiency. Prior to starting therapy, serum cortisol level measured 7.9 mcg/dL at 11 AM (normal 6.0-18.4 mcg/dL at 6-10 A.M). She had received a single dose of dexamethasone 10 mg IV with her first cycle, but not thereafter. As part of the immunotherapy protocol, serial cortisol levels were obtained, and 2 weeks after the baseline, noon serum cortisol was 1.0 ug/dL. Patient was asymptomatic. At no point were glucocorticoids replaced, but 1-week later serum cortisol level was 0.6ug/dL at 11:00 AM along with an ACTH of 5 pg/mL. Immunotherapy-induced AI was strongly suspected. Her only glucocorticoid exposure had been a dexamethasone oral mouth rinse (swish 10mL for 1 minute and spit out, four times daily). Cortisol level at 7AM a week later measured 3.5 mcg/dL with ACTH 18.7 pg/mL and a dexamethasone level 108.2 ng/dL (normal &amp;lt; 50 ng/dL for patients not on dexamethasone). Technique of swish and spit was reviewed with the patient, and she was not ingesting the medication. An observational approach was pursued at this time given hemodynamic stability, treatment was continued and several weeks later repeat labs showed cortisol levels of 3.3 (7AM), with a dexamethasone level of 84.3 ng/dL. Her course of therapy has been completed, so she has been off the dexamethasone solution, continues to be asymptomatic and repeat labs now show a 9AM Cortisol level of 9.5 mcg/dL and, given lack of other sources, it is most likely that these low cortisol levels along with elevated dexamethasone levels are related to the use of dexamethasone swish and spit rather than immunotherapy induced permanent HPA axis suppression. Conclusion: There is no literature on dexamethasone swish and spit being absorbed systemically possibly leading to potentially reversible HPA suppression. Our case will raise awareness of help guide clinicians expand their differential when working up these patients. Presentation: Friday, June 16, 2023