Immunotherapy最新文献

Autoimmune Pulmonary Alveolar Proteinosis (aPAP) is a rare disease characterized by myeloid cell dysfunction, abnormal pulmonary surfactant accumulation, and innate immune deficiency. Pathogenesis is driven by GM-CSF neutralizing autoantibodies (GMAbs) present in high titer in serum and bronchoalveolar lavage fluid (BALF) of patients. GM-CSF is a cytokine and a hematopoietic growth factor produced by a variety of cells. In the lungs, GM-CSF regulates surfactant homeostasis and lung host defense through innate immune function. Whole lung lavage (WLL) is the current first line therapy for aPAP. It is a procedure in which excessive surfactant is mechanically removed from the alveoli. Pathogenesis-driven treatment with GM-CSF augmentation has been investigated over the last two decades with recombinant GM-CSF (rGM-CSF). Molgramostim and sargramostim are rGM-CSF which can be self-administered at home by patients with aPAP either subcutaneously or using a handheld nebulizer. In Phase II and III studies of adults with aPAP, daily administration of inhaled molgramostim resulted in greater improvements in pulmonary gas transfer and functional health status than placebo, with similar rates of adverse events. In all clinical studies to date, rGM-CSF has shown a favorable safety profile with no dose limiting toxicity. This supports the application of inhaled rGM-CSF for the treatment of aPAP and the possibility of WLL as a rescue therapy.

B-cell maturation antigen (BCMA) directed chimeric antigen receptor T-cell therapy (CAR-T) has transformed the treatment of relapsed/refractory multiple myeloma (RRMM), yet relapse is still common for most patients. A variety of different salvage treatment strategies have been studied in the last several years to address several resistance mechanisms that lead to relapse after BCMA CAR-T. To date, there are no clear guidelines regarding treatment sequencing strategies for salvage therapy. This review will investigate the current landscape of available salvage therapies and data supporting their use, as well as possible treatment sequencing strategies to maximize clinical outcomes in this difficult-to-treat population.

Background and objective: This study aimed to evaluate the cost-utility analyses of blinatumomab in children with relapsed/refractory B-cell Acute Lymphoblastic Leukemia (B-ALL) compared to Consolidation Chemotherapy in Iran.

Method: Based on the results of the phase III randomized 20120215 trial (NCT02393859) the cost-utility analysis, was evaluated over a lifetime using the Parietal Survival model with three health states. The model considered both direct and indirect costs from a societal perspective. The incremental cost-effectiveness ratio (ICER) was calculated by determining the cost per quality-adjusted life year (QALY) gained. Costs and QALYs were discounted annually at 5.8% and 5%, respectively. Deterministic sensitivity analysis (DSA) and Probabilistic sensitivity analysis (PSA) were performed to assess the model's robustness.

Results: The study estimated that blinatumomab is a cost-effective treatment option, with a probability of 57.2%. Blinatumomab was associated with a higher cost ($42,481 versus $21,355) and higher QALYs gained (13.14 versus 8.06) compared to Consolidation Chemotherapy with an ICER of USD 4,160, which is below the willingness-to-pay (WTP) threshold of 4,210 USD in Iran.

Conclusions: Blinatumomab is a cost-effective treatment strategy for pediatric patients with relapsed/refractory B-cell acute lymphoblastic leukemia B-ALL from an Iranian societal perspective.

Aim: To assess the clinical relevance of B. tropicalis IgE sensitization through nasal challenge test (NCT) and explore the effectiveness of immunotherapy (AIT) with this mite.

Methods: A prospective cohort study was conducted in patients with moderate/severe persistent allergic rhinitis. In phase one, atopy tests for B. tropicalis were evaluated using NCT as reference parameter. In phase two, NCT-positive patients underwent AIT for 1 year, followed by a second NCT.

Result: Eighty patients sensitized to B. tropicalis were enrolled; 56% had a positive baseline NCT. The SPT and sIgE exhibited a sensitivity over 90%, but a specificity lower than 50% with an overall diagnostic accuracy of 64%. The sIgE to Blo t 5 exhibited a sensitivity of 59.9%, specificity of 80%, and overall diagnostic accuracy 72%. Of those with positive NCT, 39 started AIT. During the second NCT, 82% of these patients tolerated a B. tropicalis extract concentration tenfold higher than baseline.

Conclusion: B. tropicalis is clinically relevant for allergic rhinitis patients, but atopy tests for this disease have a low specificity. AIT with B. tropicalis is a therapeutic tool for allergic rhinitis, mainly when a positive-NCT is demonstrated.

Background: Oral immunotherapy (OIT) is an emerging treatment for IgE-mediated food allergy, but eosinophilic esophagitis (EoE) has been reported as a potential complication, especially with milk and egg. Data on wheat OIT are limited. This study examined the incidence, course, and outcomes of EoE in children undergoing wheat OIT.

Methods: We retrospectively reviewed 79 children with confirmed IgE-mediated wheat allergy treated with OIT between 2020 and 2023 at two tertiary centers in Iran. Patients with suspected EoE underwent endoscopy with histopathology. Diagnosis required ≥15 eosinophils/high-power field. Management included wheat elimination and proton pump inhibitors (PPIs) ± topical corticosteroids.

Results: Eight of 79 patients (10.1%) developed EoE. Seven became symptomatic during up-dosing or early maintenance; one asymptomatic patient was diagnosed at parental request. Histopathology confirmed 18-110 eosinophils/HPF. All symptomatic cases improved after OIT discontinuation and medical therapy. No severe anaphylaxis occurred. Follow-up endoscopy was limited by patient refusal.

Conclusion: EoE occurred in 10% of children during wheat OIT, mainly in the up-dosing phase. While symptoms resolved with treatment and cessation, distinguishing transient OIT-induced eosinophilia from persistent EoE remains critical. Prospective studies with pre- and post-OIT endoscopy are needed to guide monitoring and management.

With the rapid advancements in oncology, immunology, and molecular biology, immunotherapy has emerged as a cornerstone of anti-tumor treatment, complementing traditional modalities such as surgery, radiotherapy, and chemotherapy. Among the many immunotherapy strategies, adoptive cell therapy (ACT) is the most representative one. A key technology within ACT is chimeric antigen receptor (CAR) T-cell therapy, a precision-targeted treatment that leverages genetic engineering to modify T cells, enabling them to express antigen-specific receptors independent of major histocompatibility complex (MHC) restrictions. In recent years, continuous optimization of CAR-T therapy has been leading to remarkable clinical outcomes in oncology. However, its efficacy is significantly compromised by T-cell exhaustion, characterized by reduced proliferative capacity, attenuated anti-tumor activity, and limited persistence. Notably, CAR-T cell exhaustion is primarily driven by repeated tumor antigen stimulation, sustained autonomous activation of CAR constructs, and the immunosuppressive tumor microenvironment (TME), collectively contributing to disease relapse in hematologic malignancies and limited efficacy in solid tumors. Therefore, it is important to elucidate and inhibit the mechanism of CAR-T cell dysfunction to improve its efficacy. Overcoming these challenges will facilitate the development of CAR-T cells with sustained proliferative potential and tumor clearance.

Case: A 40-year-old man presented with malignant giant cell tumor of bone of the left distal femur. Despite distal femur resection/replacement and adjuvant chemotherapy, he experienced local recurrence and lung metastases. Salvage radiation therapy was ineffective. Biopsy of the tumor showed a PD-L1 tumor proportion score of 40%. Pembrolizumab was initiated and resulted in a major partial response. However, the patient experienced radiation recall pneumonitis necessitating stoppage of pembrolizumab. The patient then experienced another local recurrence.

Conclusion: PD-L1 blockade should be considered for MGCTB expressing PD-L1. Unfortunately, pembrolizumab was stopped, which likely allowed for tumor progression in this case.

CAR T cell therapy represents an emerging, promising approach in the field of autoimmune diseases. Unlike monoclonal antibodies, CAR T cells offer a deeper B cell depletion than monoclonal antibodies through their ability to infiltrate tissues and their independence from effector mechanisms. Early data from case reports and phase I/II studies demonstrate encouraging clinical responses in patients with severely refractory autoimmune disorders. CD19, BCMA and dual-targeting CAR constructs were generally well tolerated with limited safety concerns. This promising data encourages further research investigating CAR T cell therapy in a broader range of autoimmune indications and to advance CAR T constructs to improve efficacy, safety, and clinical application. In this review, we explore the rationale of using CAR T cell therapy in autoimmune diseases, summarize relevant clinical data, and highlight future perspectives within the field.

Tumor necrosis factor-alpha (TNF-α) inhibitors, notably adalimumab, represent a cornerstone in managing chronic inflammatory disorders such as ankylosing spondylitis and Crohn's disease. Despite their therapeutic efficacy, paradoxical dermatologic adverse events, including pustular eruptions, have been occasionally documented. This report presents the case of a 62-year-old Caucasian female patient who developed erythematous-pustular lesions following prolonged exposure to adalimumab. Histopathologic assessment confirmed subcorneal pustular dermatosis (SPD), characterized by subcorneal neutrophilic accumulations and focal spongiosis. Discontinuation of adalimumab and initiation of systemic corticosteroids alone led to prompt clinical resolution. This case contributes to the limited literature on anti-TNF-induced SPD, emphasizing the critical role of early recognition and interdisciplinary intervention.