Clinical Efficacy of Allergen Specific Immunotherapy (ASIT) in Allergic Rhinitis

Though efficacy of Allergen Specific Immunotherapy (ASIT) has been proved in many studies, reports about success in clinical practice and under field conditions in alleviating the suffering or decreasing the morbidity in patients of Allergic Rhinitis are few. 260 patients of Allergic Rhinitis without coexisting diseases were included. Skin prick test was done on all patients. ASIT was initiated with common inhalant indoor allergens as per standard protocol and patients were assessed at the start and at 2 m, 6 m and 18 months of ASIT. ASIT was able to significantly reduce the symptom score in all the three groups namely sneezing, rhinorrhoea and nasal itching (p < 0.001). Concurrently it was also able to produce a significant reduction in the usage of concomitant drug intake (p < 0.001) thereby implying a decrease in morbidity. When assessed regarding clinical efficacy, ASIT was found to be satisfactory or highly effective in more than 75% patients. ASIT has got a role in clinical practice in polysensitized patients in field conditions. This is based on the evidence that besides decrease in hypersensitivity/symptoms, it also has an effect on minimizing the necessity of taking drugs to relieve the symptoms, which has strong implications of economics and toxicity, while treating patients.

LMP2-DC Vaccine Elicits Specific EBV-LMP2 Response to Effectively Improve Immunotherapy in Patients with Nasopharyngeal Cancer

Objective To evaluate the safety and effectiveness of a vaccine based on latent membrane protein 2(LMP2)modified dendritic cells(DCs)that boosts specific responses of cytotoxic T lymphocytes(CTLs)to LMP2 before and after intradermal injection in patients with nasopharyngeal carcinoma(NPC).Methods DCs were derived from peripheral blood monocytes of patients with NPC.We prepared LMP2-DCs infected by recombinant adenovirus vector expressing LMP2(rAd-LMP2).NPC patients were immunized with 2×105 LMP2-DCs by intradermal injection at week 0 and after the second and fourth weeks.Specific responses to LMP2 were detected by enzyme-linked immunospot(ELISPOT)assay at week 0 and at the fifth and eighth weeks.Local clinicians performed the follow-up and tracking of patients.Results We demonstrated that DCs derived from monocytes displayed typical DC morphologies;the expression of LMP2 in the LMP2-DCs vaccine was confirmed by immunocytochemical assay.Twenty-nine patients with NPC were enrolled in this clinical trial.The LMP2-DCs vaccine was well tolerated in all of the patients.Boosted responses to LMP2 peptide sub-pools were observed in 18 of the 29 patients with NPC.The follow-up data of 29 immunized patients from April,2010 to April 2015 indicated a five-year survival rate of 94.4%in responders and 45.5%in non-responders.Conclusion In this pilot study,we demonstrated that the LMP2-DCs vaccine is safe and effective in patients with NPC.Specific CTLs responses to LMP2 play a certain role in controlling and preventing the recurrence and metastasis of NPC,which warrants further clinical testing.

Efficacy of Oral Antigen Specific Immunotherapy on Desensitization of Some Autoimmune Diseases Associated with Milk Allergy

There are several reports on the prevalence and importance of milk allergens in the induction of allergic diseases, whereas its role in the induction of autoimmune disease was rarely studied. So, the present work aimed to study the diagnosis and the efficacy of oral antigen specific immunotherapy (OAIT) on two groups of autoimmune disease patients namely, rheumatic arthritis (RA), group II, and systemic lupus erythematosus (SLE), group III, who has allergens for milk as an effective treatment option. From the assessment of the data obtained and the clinical outcome of RA and SLE patients after food elimination strategy and milk immunotherapy, it was evident that there were significant reductions (P < 0.001) in the levels of total IgE, specific IgE, Rheumatic factor (R.F), C-reactive protein (C.R.P), Anti-nuclear antibodies (ANA) and anti-double stranded DNA antibodies (Anti-ds DNA) compared to pretreated levels. Moreover, the immunotherapy induced “blocking antibodies” by remarkable highly significant increasing in IgG, phagocytic inhibition test (PIT %), Complement component 3(C3), and Complement component 4 (C4) levels. More improvement was noticed in the SLE as a result of the immunotherapy. Conclusion: milk desensitization is a gained interest and a safe valuable effective treatment of autoimmune conditions in Egypt.

Revolutionizing gastric cancer treatment:The potential of immunotherapy

Gastric cancer,a prevalent malignancy worldwide,ranks sixth in terms of frequency and third in fatality,causing over a million new cases and 769000 annual deaths.Predominant in Eastern Europe and Eastern Asia,risk factors include family medical history,dietary habits,tobacco use,Helicobacter pylori,and Epstein-Barr virus infections.Unfortunately,gastric cancer is often diagnosed at an advanced stage,leading to a grim prognosis,with a 5-year overall survival rate below 5%.Surgical intervention,particularly with D2 Lymphadenectomy,is the mainstay for early-stage cases but offers limited success.For advanced cases,the National Comprehensive Cancer Network recommends chemotherapy,radiation,and targeted therapy.Emerging immunotherapy presents promise,especially for unresectable or metastatic cases,with strategies like immune checkpoint inhibitors,tumor vaccines,adoptive immunotherapy,and nonspecific immunomodulators.In this Editorial,with regards to the article“Advances and key focus areas in gastric cancer immunotherapy:A comprehensive scientometric and clinical trial review”,we address the advances in the field of immunotherapy in gastric cancer and its future prospects.

New avenues for the treatment of immunotherapy-resistant pancreatic cancer

Pancreatic cancer(PC)is characterized by its extremely aggressive nature and ranks 14th in the number of new cancer cases worldwide.However,due to its complexity,it ranks 7th in the list of the most lethal cancers worldwide.The pathogenesis of PC involves several complex processes,including familial genetic factors associated with risk factors such as obesity,diabetes mellitus,chronic pancreatitis,and smoking.Mutations in genes such as KRAS,TP53,and SMAD4 are linked to the appearance of malignant cells that generate pancreatic lesions and,consequently,cancer.In this context,some therapies are used for PC,one of which is immunotherapy,which is extremely promising in various other types of cancer but has shown little response in the treatment of PC due to various resistance mechanisms that contribute to a drop in immunotherapy efficiency.It is therefore clear that the tumor microenvironment(TME)has a huge impact on the resistance process,since cellular and non-cellular elements create an immunosuppressive environment,characterized by a dense desmoplastic stroma with cancerassociated fibroblasts,pancreatic stellate cells,extracellular matrix,and immunosuppressive cells.Linked to this are genetic mutations in TP53 and immunosuppressive factors that act on T cells,resulting in a shortage of CD8+T cells and limited expression of activation markers such as interferon-gamma.In this way,finding new strategies that make it possible to manipulate resistance mechanisms is necessary.Thus,techniques such as the use of TME modulators that block receptors and stromal molecules that generate resistance,the use of genetic manipulation in specific regions,such as microRNAs,the modulation of extrinsic and intrinsic factors associated with T cells,and,above all,therapeutic models that combine these modulation techniques constitute the promising future of PC therapy.Thus,this study aims to elucidate the main mechanisms of resistance to immunotherapy in PC and new ways of manipulating this process,resulting in a more efficient therapy for cancer patients and,consequently,a reduction in the lethality of this aggressive cancer.

Immunotherapy in type 1 diabetes:Novel pathway to the future ahead

Since the discovery of insulin over 100 years ago,the focus of research in the management of type 1 diabetes(T1D)has centered around glycemic control and management of complications rather than the prevention of autoimmune destruc-tion of pancreaticβcells.Fortunately,in recent years,there has been significant advancement in immune-targeted pharmacotherapy to halt the natural progres-sion of T1D.The immune-targeted intervention aims to alter the underlying pa-thogenesis of T1D by targeting different aspects of the immune system.The im-munotherapy can either antagonize the immune mediators like T cells,B cells or cytokines(antibody-based therapy),or reinduce self-tolerance to pancreaticβcells(antigen-based therapy)or stem-cell treatment.Recently,the US Food and Drug Administration approved the first immunotherapy teplizumab to be used only in stage 2 of T1D.However,the window of opportunity to practically implement this approved molecule in the selected target population is limited.In this Edito-rial,we briefly discuss the various promising recent developments in the field of immunotherapy research in T1D.However,further studies of these newer thera-peutic agents are needed to explore their true potential for prevention or cure of T1D.

Peptide drugs: a new direction in cancer immunotherapy

Cancer immunotherapy has emerged as a promising approach in cancer treatment and is considered a major advancement after surgical interventions, radiotherapy, chemotherapy, and targeted therapy. The clinical use of immunotherapeutic drugs, particularly antibody-based drugs that target immune checkpoints, has notably increased~1.

Deep insight into the B-cell associated tertiary lymphoid structure and tumor immunotherapy

Bod et al.1 recently published a study in Nature that garnered attention to B cell-associated anti-tumor immunity and immunotherapy of melanoma and other tumors1.As a promising supplemental immunotherapy to mainstream methods that target T and natural killer(NK)cells,B cell-associated anti-tumor immunotherapy is promising。

Analysis of the impact of immunotherapy efficacy and safety in patients with gastric cancer and liver metastasis

BACKGROUND Gastric cancer(GC)is the fifth most common type of cancer and has the fourth highest death rate among all cancers.There is a lack of studies examining the impact of liver metastases on the effectiveness of immunotherapy in individuals diagnosed with GC.AIM To investigate the influence of liver metastases on the effectiveness and safety of immunotherapy in patients with advanced GC.METHODS This retrospective investigation collected clinical data of patients with advanced stomach cancer who had immunotherapy at our hospital from February 2021 to January 2023.The baseline attributes were compared using either the Chi-square test or the Fisher exact probability method.The chi-square test and Kaplan-Meier survival analysis were employed to assess the therapeutic efficacy and survival duration in GC patients with and without liver metastases.RESULTS The analysis comprised 48 patients diagnosed with advanced GC,who were categorized into two groups:A liver metastasis cohort(n=20)and a non-liver metastatic cohort(n=28).Patients with liver metastasis exhibited a more deteriorated physical condition compared to those without liver metastasis.The objective response rates in the cohort with metastasis and the cohort without metastasis were 15.0%and 35.7%(P>0.05),respectively.Similarly,the disease control rates in these two cohorts were 65.0%and 82.1%(P>0.05),respectively.The median progression-free survival was 5.0 months in one group and 11.2 months in the other group,with a hazard ratio of 0.40 and a significance level(P)less than 0.05.The median overall survival was 12.0 months in one group and 19.0 months in the other group,with a significance level(P)greater than 0.05.CONCLUSION Immunotherapy is less effective in GC patients with liver metastases compared to those without liver metastasis.

Present situation and prospect of immunotherapy for unresectable locally advanced esophageal cancer during peri-radiotherapy

Four major studies(Checkmate577,Keynote-590,Checkmate649 and Attraction-4)of locally advanced esophageal cancer published in 2020 have established the importance of immunotherapy,represented by anti-programmed death protein(PD)-1 in postoperative adjuvant treatment and advanced first-line treatment of locally advanced or advanced esophageal cancer and esophagogastric junction cancer,from the aspects of proof of concept,long-term survival,overall survival rate and progression-free survival.For unresectable or inoperable nonmetastatic esophageal cancer,concurrent radiotherapy and chemotherapy is the standard treatment recommended by various guidelines.Because its curative effect is still not ideal,it is necessary to explore radical radiotherapy and chemotherapy in the future,and it is considered to be promising to combine them with immunotherapeutic drugs such as anti-PD-1.This paper mainly discusses how to combine radical concurrent radiotherapy and chemotherapy with immunotherapy for unresectable local advanced esophageal cancer.

Immunotherapy of gastric cancer:Present status and future perspectives

In this editorial,we comment on the article entitled“Advances and key focus areas in gastric cancer immunotherapy:A comprehensive scientometric and clinical trial review(1999-2023),”which was published in the recent issue of the World Journal of Gastroenterology.We focused on the results of the authors’bibliometric analysis concerning gastric cancer immunotherapy,which they analyzed in depth by compiling the relevant publications of the last 20 years.Before that,we briefly describe the most recent data concerning the epidemiological parameters of gastric cancer(GC)in different countries,attempting to give an interpretation based on the etiological factors involved in the etiopathogenesis of the neoplasm.We then briefly discuss the conservative treatment(chemotherapy)of the various forms of this malignant neoplasm.We describe the treatment of resectable tumors,locally advanced neoplasms,and unresectable(advanced)cases.Special attention is given to modern therapeutic approaches with emphasis on immunotherapy,which seems to be the future of GC treatment,especially in combination with chemotherapy.There is also a thorough analysis of the results of the study under review in terms of the number of scientific publications,the countries in which the studies were conducted,the authors,and the scientific centers of origin,as well as the clinical studies in progress.Finally,an attempt is made to draw some conclusions and to point out possible future directions.

Efficacy of Bispecific Antibody Targeting EpCAM and CD3 for Immunotherapy in Ovarian Cancer Ascites:An Experimental Study

Objective This study aimed to explore the value of M701,targeting epithelial cell adhesion molecule(EpCAM)and CD3,in the immunotherapy of ovarian cancer ascites by the in vitro assay.Methods The expression of EpCAM in ovarian cancer tissues was analyzed by databases.The EpCAM expression and immune cell infiltration in different foci of ovarian cancer were detected by 8-channel flow cytometry.The toxic effect of M701 on OVCAR3 was tested using the in vitro cytotoxicity assay.The 3D cell culture and drug intervention experiments were performed to evaluate the therapeutic effect of M701 in ovarian cancer specimens.Flow cytometry was used to examine the effect of M701 on the binding of immune cells to tumor cells and the activation capacity of T cells.Results The results of the bioinformatic analysis showed that the expression of EpCAM in ovarian cancer tissue was significantly higher than that in normal ovarian tissue.The 8-channel flow cytometry of clinical samples showed that the EpCAM expression and lymphocyte infiltration were significantly heterogeneous among ovarian cancer patients and lesions at different sites.The in vitro experiment results showed that M701 had a significant killing effect on OVCAR3 cells.M701 also obviously killed primary tumor cells derived from some patients with ovarian cancer ascites.M701 could mediate the binding of CD3^(+)T cells to EpCAM^(+)tumor cells and induce T cell activation in a dose-dependent manner.Conclusion M701 showed significant inhibitory activity on tumor cells derived from ovarian cancer ascites,which had a promising application in immunotherapy for patients with ovarian cancer ascites.

Immunotherapy for esophageal cancer:Where are we now and where can we go

Immune checkpoint inhibitor therapy has dramatically improved patient prognosis,and thereby transformed the treatment in various cancer types including esophageal squamous cell carcinoma(ESCC)in the past decade.Monoclonal antibodies that selectively inhibit programmed cell death-1(PD-1)activity has now become standard of care in the treatment of ESCC in metastatic settings,and has a high expectation to provide clinical benefit during perioperative period.Further,anti-cytotoxic T-lymphocyte–associated protein 4(CTLA-4)monoclonal antibody has also been approved in the treatment of recurrent/metastatic ESCC in combination with anti-PD-1 antibody.Well understanding of the existing evidence of immune-based treatments for ESCC,as well as recent clinical trials on various combinations with chemotherapy for different clinical settings including neoadjuvant,adjuvant,and metastatic diseases,may provide future prospects of ESCC treatment for better patient outcomes.

Advancements in Lynch Syndrome Management: Applying Immunotherapy for Therapeutic Success

Lynch syndrome is the fourth most common cancer in the United States, with an early age of onset and poor prognosis. Here, we present a unique case of a patient with progressive colon cancer due to a late diagnosis of Lynch syndrome showing excellent response to immunotherapy. A 59-year-old male with a history of rectal cancer 30 years ago came to the hospital due to a fever and further found a large necrotic colon mass. Biopsy was positive for colorectal cancer;however, due to the size of the tumor, the patient was deemed not a surgical candidate and offered hospice with palliative chemotherapy. Based on further workup, the patient was diagnosed with Lynch syndrome, with colon cancer determined to be responsive to Immunotherapy. He was started on JEMPERLI (Dosterlimab-gxly), and after three cycles of therapy, imaging and PET scan were repeated, showing decreased activity and extent of the tumor—a tremendous success.

Gastric cancer immunotherapy:A scientometric and clinical trial review

This letter is intended to arouse your interest in a recent review of comprehensive scientometrics and clinical trials on immunotherapy for gastric cancer(GC).Our study reviews recent advances in immunotherapy in the field of GC and highlights its new prospects as a treatment for GC.Our research reveals China’s leadership in this field,as well as new therapeutic strategies such as immune checkpoint inhibitors,cellular immunotherapy,and vaccines.The combined findings highlight the potential of immunotherapy to improve survival and quality of life in patients with stomach cancer.We believe that this study will provide important guidance for the future direction of the GC treatment field.

Immune status and combined immunotherapy progression in Kirsten rat sarcoma viral oncogene homolog(KRAS)-mutant tumors

Kirsten rat sarcoma viral oncogene homolog(KRAS)is the most frequently mutated oncogene,occurring in various tumor types.Despite extensive efforts over the past 40 years to develop inhibitors targeting KRAS mutations,resistance to these inhibitors has eventually emerged.A more precise understanding of KRAS mutations and the mechanism of resistance development is essential for creating novel inhibitors that target specifically KRAS mutations and can delay or overcome resistance.Immunotherapy has developed rapidly in recent years,and in-depth dissection of the tumor immune microenvironment has led researchers to shift their focus to patients with KRAS mutations,finding that immune factors play an essential role in KRAS-mutant(KRAS-Mut)tumor therapy and targeted drug resistance.Breakthroughs and transitions from targeted therapy to immunotherapy have provided new hope for treating refractory patients.Here,we reviewed KRAS mutation-targeted treatment strategies and resistance issues,focusing on our in-depth exploration of the specific immune status of patients with KRAS mutations and the impact of body immunity following KRAS inhibition.We aimed to guide innovative approaches combining RAS inhibition with immunotherapy,review advances in preclinical and clinical stages,and discuss challenges and future directions.

Identifying Comprehensive Genomic Alterations and Potential Neoantigens for Cervical Cancer Immunotherapy in a Cohort of Chinese Squamous Cell Carcinoma of the Cervix

Objective Genomic alterations and potential neoantigens for cervical cancer immunotherapy were identified in a cohort of Chinese patients with cervical squamous cell carcinoma(CSCC).Methods Whole-exome sequencing was used to identify genomic alterations and potential neoantigens for CSCC immunotherapy.RNA Sequencing was performed to analyze neoantigen expression.Results Systematic bioinformatics analysis showed that C>T/G>A transitions/transversions were dominant in CSCCs.Missense mutations were the most frequent types of somatic mutation in the coding sequence regions.Mutational signature analysis detected signature 2,signature 6,and signature 7 in CSCC samples.PIK3CA,FBXW7,and BICRA were identified as potential driver genes,with BICRA as a newly reported gene.Genomic variation profiling identified 4,960 potential neoantigens,of which 114 were listed in two neoantigen-related databases.Conclusion The present findings contribute to our understanding of the genomic characteristics of CSCC and provide a foundation for the development of new biotechnology methods for individualized immunotherapy in CSCC.

Efficacy of a Diabetes Specific Nutrition Supplement on Glycemic, Anthropometric, Dietary and Gut Health Markers in Adults with Type 2 Diabetes: An RCT

With increasing incidence of diabetes, use of diabetes specific nutrition supplements (DSNS) is common for better management of the disease. To study effect of 12-week DSNS supplementation on glycemic markers, anthropometry, lipid profile, SCFAs, and gut microbiome in individuals with diabetes. Markers studied were glycemic [Fasting Blood Glucose (FBG), Post Prandial Glucose (PPG), HbA1c, Incremental Area under curve (iAUC), Mean Amplitude of Glycemic Excursions (MAGE), Time in/above Range (TIR/TAR)], anthropometry [weight, Body Mass Index (BMI), waist circumference (WC)], lipid profile, diet and gut health [plasma short chain fatty acids (SCFAs)]. N = 210 adults were randomized to receive either DSNS with standard care (DSNS + SC;n = 105) or standard care alone (SC alone;n = 105). After 12 weeks, significant differences between DSNS + SC versus SC alone was observed in FBG [−3 ± 6 vs 14 ± 6 mg/dl;p = 0.03], PPG [−35 ± 9 vs −3 ± 9 mg/dl;p = 0.01], weight [−0.6 ± 0.1 vs 0.2 ± 0.1 kg;p = 0.0001], BMI [−0.3 ± 0.1 vs 0.1 ± 0.1 kg/m2;p = 0.0001] and WC [−0.3 ± 0.2 vs 0.2 ± 0.2 cm;p = 0.01]. HbA1C and low-density lipoprotein (LDL) were significantly reduced in DSNS + SC [−0.2 ± 0.9;p = 0.04 and −5 mg/dl;p = 0.03] respectively with no change in control. Continuous Glucose Monitoring (CGM) reported significant differences between DSNS + SC versus SC alone for mean glucose [−12 ± 65 vs 28 ± 93 mg/dl;p < 0.01], TAR 180 [−9 ± 42 vs 7 ± 45 mg/dl;p = 0.04], TAR 250 [−3 ± 27 vs 9 ± 38 mg/dl;p = 0.05], iAUC [−192 (1.1) vs −48 (1.1) mg/dl;p = 0.03]. MAGE was significantly reduced for both DSNS + SC (−19 ± 67;p < 0.001) and SC alone (−8 ± 70;p = 0.04), with reduction being more pronounced for DSNS + SC. DSNS + SC reported a decrease in carbohydrate energy % [−9.4 (−11.3, −7.6) %;p < 0.0001] and amount [−47.4 (−67.1, −27.7) g;p < 0.0001], increased dietary fiber [9.5 (7.2, 11.8) g;p < 0.0001] and protein energy % [0.9 (0.5, 1.3) %;p < 0.0001] versus SC alone. DSNS + SC reported significant increases versus SC alone in total (0.3 ng/ml;p = 0.03) and individual plasma SCFAs. The consumption of DSNS significantly improves the glycemic, anthropometric, dietary, and gut health markers in diabetes.

Codelivery of anti-CD47 antibody and chlorin e6 using a dual pH-sensitive nanodrug for photodynamic immunotherapy of osteosarcoma

Osteosarcoma is a malignant tumor originating from bone tissue that progresses rapidly and has a poor patient prognosis.Immunotherapy has shown great potential in the treatment of osteosarcoma.However,the immunosuppressive microenvironment severely limits the efficacy of osteosarcoma treatment.The dual pH-sensitive nanocarrier has emerged as an effective antitumor drug delivery system that can selectively release drugs into the acidic tumor microenvironment.Here,we prepared a dual pH-sensitive nanocarrier,loaded with the photosensitizer Chlorin e6(Ce6)and CD47 monoclonal antibodies(aCD47),to deliver synergistic photodynamic and immunotherapy of osteosarcoma.On laser irradiation,Ce6 can generate reactive oxygen species(ROS)to kill cancer cells directly and induces immunogenic tumor cell death(ICD),which further facilitates the dendritic cell maturation induced by blockade of CD47 by aCD47.Moreover,both calreticulin released during ICD and CD47 blockade can accelerate phagocytosis of tumor cells by macrophages,promote antigen presentation,and eventually induce T lymphocyte-mediated antitumor immunity.Overall,the dual pH-sensitive nanodrug loaded with Ce6 and aCD47 showed excellent immune-activating and anti-tumor effects in osteosarcoma,which may lay the theoretical foundation for a novel combination model of osteosarcoma treatment.

Progress of Immunotherapy Combined with Anti-Angiogenesis Therapy in Lung Cancer

Lung cancer is the most prevalent and fatal cancer in China and even around the world, and many patients are found in the late stage of lung cancer. For the treatment of advanced lung cancer, in addition to traditional chemotherapy modalities, many emerging treatments are increasingly significant, such as immunotherapy, anti-angiogenic therapy, and targeted therapy. An increasing number of studies have now shown that anti-angiogenic therapy improves the immune microenvironment by enhancing tumor immunity through normalization of tumor vessels. Immunization combined with anti-angiogenic therapy can exert synergistic effects and improve the prognosis of patients. This article summarizes the extent of benefit, current clinical study data, and future prospects of immunotherapy combined with anti-angiogenic agents in the treatment of advanced NSCLC.