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Tomography (Ann Arbor, Mich.) Jun 2024CAR-T-cell therapy, also referred to as chimeric antigen receptor T-cell therapy, is a novel method in the field of immunotherapy for the treatment of non-Hodgkin's... (Review)
Review
CAR-T-cell therapy, also referred to as chimeric antigen receptor T-cell therapy, is a novel method in the field of immunotherapy for the treatment of non-Hodgkin's lymphoma (NHL). In patients receiving CAR-T-cell therapy, fluorodeoxyglucose Positron Emission Tomography/Computer Tomography ([F]FDG PET/CT) plays a critical role in tracking treatment response and evaluating the immunotherapy's overall efficacy. The aim of this study is to provide a systematic review of the literature on the studies aiming to assess and predict toxicity by means of [F]FDG PET/CT in patients with NHL receiving CAR-T-cell therapy. PubMed/MEDLINE and Cochrane Central Register of Controlled Trials (CENTRAL) databases were interrogated by two investigators to seek studies involving the use of [F]FDG PET/CT in patients with lymphoma undergoing CAR-T-cell therapy. The comprehensive computer literature search allowed 11 studies to be included. The risk of bias for the studies included in the systematic review was scored as low by using version 2 of the "Quality Assessment of Diagnostic Accuracy Studies" tool (QUADAS-2). The current literature emphasizes the role of [F]FDG PET/CT in assessing and predicting toxicity in patients with NHL receiving CAR-T-cell therapy, highlighting the evolving nature of research in CAR-T-cell therapy. Additional studies are warranted to increase the collected evidence in the literature.
Topics: Humans; Fluorodeoxyglucose F18; Positron Emission Tomography Computed Tomography; Lymphoma, Non-Hodgkin; Immunotherapy, Adoptive; Radiopharmaceuticals; Receptors, Chimeric Antigen; Treatment Outcome
PubMed: 38921943
DOI: 10.3390/tomography10060066 -
Molecular Cancer Jun 2024Tumor immune microenvironment (TIME) consists of intra-tumor immunological components and plays a significant role in tumor initiation, progression, metastasis, and... (Review)
Review
Tumor immune microenvironment (TIME) consists of intra-tumor immunological components and plays a significant role in tumor initiation, progression, metastasis, and response to therapy. Chimeric antigen receptor (CAR)-T cell immunotherapy has revolutionized the cancer treatment paradigm. Although CAR-T cell immunotherapy has emerged as a successful treatment for hematologic malignancies, it remains a conundrum for solid tumors. The heterogeneity of TIME is responsible for poor outcomes in CAR-T cell immunotherapy against solid tumors. The advancement of highly sophisticated technology enhances our exploration in TIME from a multi-omics perspective. In the era of machine learning, multi-omics studies could reveal the characteristics of TIME and its immune resistance mechanism. Therefore, the clinical efficacy of CAR-T cell immunotherapy in solid tumors could be further improved with strategies that target unfavorable conditions in TIME. Herein, this review seeks to investigate the factors influencing TIME formation and propose strategies for improving the effectiveness of CAR-T cell immunotherapy through a multi-omics perspective, with the ultimate goal of developing personalized therapeutic approaches.
Topics: Humans; Tumor Microenvironment; Neoplasms; Immunotherapy, Adoptive; Receptors, Chimeric Antigen; Animals; Genomics; T-Lymphocytes
PubMed: 38918817
DOI: 10.1186/s12943-024-02047-2 -
Blood Advances Jun 2024
Topics: Humans; Immunotherapy, Adoptive; Receptors, Chimeric Antigen; T-Lymphocytes; Receptors, Antigen, T-Cell
PubMed: 38916899
DOI: 10.1182/bloodadvances.2024013146 -
Frontiers in Immunology 2024Chimeric antigen receptor (CAR) T-cell therapy (CAR T therapy) is a treatment option for patients with relapsed or refractory multiple myeloma that has led to...
INTRODUCTION
Chimeric antigen receptor (CAR) T-cell therapy (CAR T therapy) is a treatment option for patients with relapsed or refractory multiple myeloma that has led to unprecedented treatment outcomes. Among CAR T therapies available, ciltacabtagene autoleucel (cilta-cel) is a good candidate for outpatient administration due to its generally predictable safety profile. There are multiple advantages of outpatient administration of cilta-cel, including reduced healthcare burden, expanded access, and patient autonomy. This mixed methods qualitative study aimed to identify key factors for outpatient administration of CAR T and best practice recommendations by combining a targeted literature review with expert interviews and panels.
METHODS
The targeted review (Phase 1) aimed to identify factors for outpatient CAR T administration in the US and determine key topics for the exploratory interviews (Phase 2) and expert panels (Phase 3), which aimed to inform on best practices and challenges of outpatient CAR T administration (focusing on cilta-cel). Participants in clinical and administrative positions based in treatment centers that had experience with real-world outpatient administration of cilta-cel were recruited.
RESULTS
Seventeen studies were identified in Phase 1. Key factors for outpatient administration included the development of protocols for CAR T complications, education for caregivers, outpatient specialists, hospital staff, and emergency services staff for identification and referral after possible adverse events, the creation of multidisciplinary teams for effective communication and management, straightforward patient intake processes encompassing financial eligibility review and provision of patient education materials, and close patient monitoring throughout the treatment journey. In Phase 2, 5 participants from 2 centers were interviewed. In Phase 3, 14 participants across 6 treatment centers were interviewed. Two 90-minute virtual panel discussions took place. All participants agreed that cilta-cel can be safely and effectively administered in an outpatient setting. Key recommendations included the creation of educational resources for patients and caregivers, the development of standard operating procedures, dedicated outpatient infrastructure and establishment of interdisciplinary teams, outpatient monitoring for toxicity management, and monitoring of the reimbursement landscape.
DISCUSSION
This study offers a comprehensive understanding of the feasibility of outpatient cilta-cel administration in participating CAR T centers and provides actionable recommendations while acknowledging existing challenges.
Topics: Humans; Multiple Myeloma; Immunotherapy, Adoptive; Outpatients; Biological Products; Ambulatory Care; Receptors, Chimeric Antigen; Male
PubMed: 38915401
DOI: 10.3389/fimmu.2024.1405452 -
Journal of Hematology & Oncology Jun 2024Significant advances have been made in chimeric antigen receptor T (CAR-T)-cell therapy for the treatment of recurrent or refractory B-cell hematologic malignancies.... (Review)
Review
Significant advances have been made in chimeric antigen receptor T (CAR-T)-cell therapy for the treatment of recurrent or refractory B-cell hematologic malignancies. However, CAR-T-cell therapy has not yet achieved comparable success in the management of aggressive T-cell malignancies. This article reviews the challenges of CAR-T-cell therapy in treating T-cell malignancies and summarizes the progress of preclinical and clinical studies in this area. We present an analysis of clinical trials of CAR-T-cell therapies for the treatment of T-cell malignancies grouped by target antigen classification. Moreover, this review focuses on the major challenges encountered by CAR-T-cell therapies, including the nonspecific killing due to T-cell target antigen sharing and contamination with cell products during preparation. This review discusses strategies to overcome these challenges, presenting novel therapeutic approaches that could enhance the efficacy and applicability of CAR-T-cell therapy in the treatment of T-cell malignancies. These ideas and strategies provide important information for future studies to promote the further development and application of CAR-T-cell therapy in this field.
Topics: Humans; Immunotherapy, Adoptive; Receptors, Chimeric Antigen; T-Lymphocytes; Hematologic Neoplasms; Animals; Receptors, Antigen, T-Cell
PubMed: 38915099
DOI: 10.1186/s13045-024-01568-z -
PLoS Neglected Tropical Diseases Jun 2024Salmonella enterica serotype Typhi (Salmonella Typhi) causes severe and occasionally life-threatening disease, transmitted through contaminated food and water. Humans...
BACKGROUND
Salmonella enterica serotype Typhi (Salmonella Typhi) causes severe and occasionally life-threatening disease, transmitted through contaminated food and water. Humans are the only reservoir, inadequate water, sanitation, and hygiene infrastructure increases risk of typhoid. High-quality data to assess spatial and temporal relationships in disease dynamics are scarce.
METHODS
We analyzed data from a prospective cohort conducted in an urban slum area of Dhaka City, Bangladesh. Passive surveillance at study centers identified typhoid cases by microbiological culture. Each incident case (index case) was matched to two randomly selected index controls, and we measured typhoid incidence in the population residing in a geographically defined region surrounding each case and control. Spatial clustering was evaluated by comparing the typhoid incidence in residents of geometric rings of increasing radii surrounding the index cases and controls over 28 days. Temporal clustering was evaluated by separately measuring incidence in the first and second 14-day periods following selection. Incidence rate ratios (IRRs) were calculated using Poisson regression models.
RESULTS
We evaluated 141 typhoid index cases. The overall typhoid incidence was 0.44 per 100,000 person-days (PDs) (95% CI: 0.40, 0.49). In the 28 days following selection, the highest typhoid incidence (1.2 per 100,000 PDs [95% CI: 0.8, 1.6]) was in the innermost cluster surrounding index cases. The IRR in this innermost cluster was 4.9 (95% CI: 2.4, 10.3) relative to the innermost control clusters. Neither typhoid incidence rates nor relative IRR between index case and control populations showed substantive differences in the first and second 14-day periods after selection.
CONCLUSION
In the absence of routine immunization programs, geographic clustering of typhoid cases suggests a higher intensity of typhoid risk in the population immediately surrounding identified cases. Further studies are needed to understand spatial and temporal trends and to evaluate the effectiveness of targeted vaccination in disrupting typhoid transmission.
PubMed: 38913735
DOI: 10.1371/journal.pntd.0012273 -
Frontiers in Immunology 2024The majority of patients with thyroid cancer can attain a favorable prognosis with a comprehensive treatment program based on surgical treatment. However, the current... (Review)
Review
The majority of patients with thyroid cancer can attain a favorable prognosis with a comprehensive treatment program based on surgical treatment. However, the current treatment options for advanced thyroid cancer are still limited. In recent years, chimeric antigen receptor-modified T-cell (CAR-T) therapy has received widespread attention in the field of oncology treatment. It has achieved remarkable results in the treatment of hematologic tumors. However, due to the constraints of multiple factors, the therapeutic efficacy of CAR-T therapy for solid tumors, including thyroid cancer, has not yet met expectations. This review outlines the fundamental structure and treatment strategies of CAR-T cells, provides an overview of the advancements in both preclinical investigations and clinical trials focusing on targets associated with CAR-T cell therapy in treating thyroid cancer, and discusses the challenges and solutions to CAR-T cell therapy for thyroid cancer. In conclusion, CAR-T cell therapy is a promising therapeutic approach for thyroid cancer, and we hope that our review will provide a timely and updated study of CAR-T cell therapy for thyroid cancer to advance the field.
Topics: Humans; Thyroid Neoplasms; Immunotherapy, Adoptive; Receptors, Chimeric Antigen; Animals; T-Lymphocytes; Clinical Trials as Topic; Treatment Outcome
PubMed: 38911868
DOI: 10.3389/fimmu.2024.1411300 -
Drug, Healthcare and Patient Safety 2024The manifestation and spread of neuroinvasive circulating vaccine-derived polioviruses (cVDPVs) across several countries, which led to the emergency use of the novel...
BACKGROUND
The manifestation and spread of neuroinvasive circulating vaccine-derived polioviruses (cVDPVs) across several countries, which led to the emergency use of the novel oral polio vaccine type 2 (nOPV2), raised concerns about adverse events following immunization (AEFI) surveillance. We assessed the attributes of AEFI with nOPV2 and examined stakeholder experiences and challenges in AEFI surveillance in Sierra Leone.
METHODS
Using a mixed method approach, we retrospectively reviewed passive data collected during a 2021 immunization campaign, and conducted semi-structured, interviews with vaccinators, district AEFI focal persons, and key stakeholders at the national Expanded Program on Immunization and the National Medicines Regulatory Authority. AEFI were categorized using the Medical Dictionary for Regulatory Activities (MedDRA) Preferred Terms (PTs) and System Organ Class (SOC). Outcomes were stratified as recovered or not, with preventability and causality assessed using the Schumock and Thornton and World Health Organization (WHO) algorithms, respectively.
RESULTS
A total of 528 suspected AEFI were documented, predominantly affecting children aged 28 days to 23 months (63.3%). Most reported AEFI were administration site conditions and general disorders, with pyrexia being the predominant PT. Of 80 serious cases, 78 recovered, with 74 having an inconsistent causal relationship with the vaccine. Most serious cases (78) were deemed non-preventable, with only two being probably preventable. AEFI reporting was not routinely carried out across the group of people interviewed. AEFI reporting was not consistently performed, with discrepancies in defining reportable events and confusion over responsibility. Challenges with the open data kit (ODK) platform were noted, along with perceived inadequacies in training.
CONCLUSION
While the nOPV2 is relatively new, the majority of AEFI were not serious, and most serious cases were not causally linked to the vaccine. Participants exhibited variations in experience and awareness of AEFI reporting.
PubMed: 38911456
DOI: 10.2147/DHPS.S466039 -
Cancer Control : Journal of the Moffitt... 2024Chimeric antigen receptor T cell therapy is used to treat hematological malignancies which are refractory to standard therapy. It is a form of immunotherapy in which a... (Review)
Review
Chimeric antigen receptor T cell therapy is used to treat hematological malignancies which are refractory to standard therapy. It is a form of immunotherapy in which a patient's T cells are programmed to act against tumor cells. We discuss the process of manufacturing CAR-T cells, the common side effects of therapy, and the recent emerging risk of T-cell malignancies after treatment.
Topics: Humans; Immunotherapy, Adoptive; Receptors, Chimeric Antigen; T-Lymphocytes; Hematologic Neoplasms; Receptors, Antigen, T-Cell
PubMed: 38910268
DOI: 10.1177/10732748241263713 -
Journal of Dairy Science Jun 2024Because calves are born with low levels of antibodies, effective colostrum management is one of the most critical factors for successful calf rearing. A timely and...
Because calves are born with low levels of antibodies, effective colostrum management is one of the most critical factors for successful calf rearing. A timely and adequate supply of sufficiently high-quality colostrum immediately after birth is essential to ensure the passive immunization of calves. Frozen colostrum reserves are recommended to fulfill the immunological and nutrient requirements of newborn calves, even in exceptional situations; however, the implementation rates on German dairy farms and challenges of realization remain unclear. A 33-question online survey, focused on frozen colostrum reserves, was developed to obtain an overview of colostrum management practices on German dairy farms. The questionnaire was divided into 3 sections: 1. personal data; 2. farm characteristics; 3. colostrum management. Of the 155 responses we received, 63.9% were from female farmers, and 35.5% were from male farmers. Conventional farming was practiced on 89.0% of farms, and organic farming was practiced on 7.1% of farms. Of the respondents, 89.0% froze colostrum. The main reasons for freezing colostrum were: 1. the dam does not produce enough colostrum; 2. the dam cannot be milked; or 3. in cases where the dam dies during birth. Farmers primarily froze colostrum from cows during their third to fifth lactation. Before freezing, 33.1% of the respondents measured indicators in the colostrum to estimate Ig concentrations, whereas 2.3% determined the colostrum quality after freezing. Reusable and disposable PET deposits (23.1%, 22.3%) and ColostroBags (20.0%) were the primary containers used to freeze colostrum. The main reasons for not freezing colostrum were the high labor intensity and the availability of fresh colostrum from other cows. Thawing methods included buckets (47.7%) and professional water baths (13.8%). The survey identified areas in which improved knowledge transfer could enhance colostrum management. Furthermore, there appeared to be a lack of specific, feasible instructions for employees concerning the practical implementation of colostrum management. Most importantly, the regular determination and documentation of Ig concentrations should be emphasized. The added value of stored colostrum, relative to a greater workload, should also be promoted, particularly on smaller farms.
PubMed: 38908701
DOI: 10.3168/jds.2024-24716