-
Zhongguo Shi Yan Xue Ye Xue Za Zhi Jun 2024Chimeric antigen receptor T (CAR-T) cell therapy is a rapidly developing new immunotherapy in recent years. Compared with other therapies, CAR-T has significant... (Review)
Review
Chimeric antigen receptor T (CAR-T) cell therapy is a rapidly developing new immunotherapy in recent years. Compared with other therapies, CAR-T has significant advantages for high-risk and relapsed/refractory B cell non-Hodgkin's lymphoma (B-NHL) patients. Currently, a variety of anti-CD19 CAR-T cells have been approved by the FDA for the treatment of B-NHL, such as axicabtagene ciloleucel, tisagenlecucel, lisocababtagene maraleucel and brexucabtagene autoleucel. In addition, many studies are actively exploring and developing different targeted CAR-T cells, which show great potential in B-NHL. This review briefly summarized the latest research progress on the application of CAR-T in common B-NHL.
Topics: Humans; Immunotherapy, Adoptive; Receptors, Chimeric Antigen; Lymphoma, B-Cell; Antigens, CD19; Lymphoma, Non-Hodgkin; Receptors, Antigen, T-Cell; T-Lymphocytes; Immunotherapy; Biological Products
PubMed: 38926998
DOI: 10.19746/j.cnki.issn.1009-2137.2024.03.050 -
Zhongguo Shi Yan Xue Ye Xue Za Zhi Jun 2024Chimeric antigen receptor (CAR) T cell therapy, one of the most promising tumor treatments, combines the targeted recognition of antigen and antibody with the killing... (Review)
Review
Chimeric antigen receptor (CAR) T cell therapy, one of the most promising tumor treatments, combines the targeted recognition of antigen and antibody with the killing effect of T cells. CAR-T has shown a strong therapeutic effect in lymphoid tumors and been applied in clinical practice. However, in the treatment of acute myeloid leukemia (AML), no effective and specific target like CD19 in lymphoid tumors has been found. Therefore, the key research direction is to try multiple probabilities and use optimization strategies to enhance efficacy and reduce toxicity. This review introduces the latest research progress of AML targets in CAR-T therapy in recent years, analyzes the related problems that need to be solved at present, and summarizes the optimization construction strategies mentioned in the research. Hope it can provide reference for related research and clinical application of related product.
Topics: Humans; Leukemia, Myeloid, Acute; Receptors, Chimeric Antigen; Immunotherapy, Adoptive; T-Lymphocytes; Receptors, Antigen, T-Cell; Antigens, CD19
PubMed: 38926997
DOI: 10.19746/j.cnki.issn.1009-2137.2024.03.049 -
BMC Infectious Diseases Jun 2024There is a need to understand the relationship between COVID-19 Convalescent Plasma (CCP) anti-SARS-CoV-2 IgG levels and clinical outcomes to optimize CCP use. This... (Meta-Analysis)
Meta-Analysis
BACKGROUND
There is a need to understand the relationship between COVID-19 Convalescent Plasma (CCP) anti-SARS-CoV-2 IgG levels and clinical outcomes to optimize CCP use. This study aims to evaluate the relationship between recipient baseline clinical status, clinical outcomes, and CCP antibody levels.
METHODS
The study analyzed data from the COMPILE study, a meta-analysis of pooled individual patient data from 8 randomized clinical trials (RCTs) assessing the efficacy of CCP vs. control, in adults hospitalized for COVID-19 who were not receiving mechanical ventilation at randomization. SARS-CoV-2 IgG levels, referred to as 'dose' of CCP treatment, were retrospectively measured in donor sera or the administered CCP, semi-quantitatively using the VITROS Anti-SARS-CoV-2 IgG chemiluminescent immunoassay (Ortho-Clinical Diagnostics) with a signal-to-cutoff ratio (S/Co). The association between CCP dose and outcomes was investigated, treating dose as either continuous or categorized (higher vs. lower vs. control), stratified by recipient oxygen supplementation status at presentation.
RESULTS
A total of 1714 participants were included in the study, 1138 control- and 576 CCP-treated patients for whom donor CCP anti-SARS-CoV2 antibody levels were available from the COMPILE study. For participants not receiving oxygen supplementation at baseline, higher-dose CCP (/control) was associated with a reduced risk of ventilation or death at day 14 (OR = 0.19, 95% CrI: [0.02, 1.70], posterior probability Pr(OR < 1) = 0.93) and day 28 mortality (OR = 0.27 [0.02, 2.53], Pr(OR < 1) = 0.87), compared to lower-dose CCP (/control) (ventilation or death at day 14 OR = 0.79 [0.07, 6.87], Pr(OR < 1) = 0.58; and day 28 mortality OR = 1.11 [0.10, 10.49], Pr(OR < 1) = 0.46), exhibiting a consistently positive CCP dose effect on clinical outcomes. For participants receiving oxygen at baseline, the dose-outcome relationship was less clear, although a potential benefit for day 28 mortality was observed with higher-dose CCP (/control) (OR = 0.66 [0.36, 1.13], Pr(OR < 1) = 0.93) compared to lower-dose CCP (/control) (OR = 1.14 [0.73, 1.78], Pr(OR < 1) = 0.28).
CONCLUSION
Higher-dose CCP is associated with its effectiveness in patients not initially receiving oxygen supplementation, however, further research is needed to understand the interplay between CCP anti-SARS-CoV-2 IgG levels and clinical outcome in COVID-19 patients initially receiving oxygen supplementation.
Topics: Humans; COVID-19; Immunization, Passive; COVID-19 Serotherapy; Antibodies, Viral; SARS-CoV-2; Male; Middle Aged; Female; Immunoglobulin G; Aged; Treatment Outcome; Adult; Retrospective Studies; Randomized Controlled Trials as Topic
PubMed: 38926676
DOI: 10.1186/s12879-024-09529-0 -
Journal of Clinical and Experimental... 2024Patients with refractory or relapsed (R/R) large B-cell lymphoma (LBCL) refractory to first-line chemotherapy or with early relapse have poor outcomes. While chimeric...
Patients with refractory or relapsed (R/R) large B-cell lymphoma (LBCL) refractory to first-line chemotherapy or with early relapse have poor outcomes. While chimeric antigen receptor (CAR) T-cell therapy has impressive efficacy after two or more lines of chemotherapy, it's still uncertain if these outcomes remain consistent in the context of third-line CAR T-cell therapy. We conducted a retrospective study of 107 R/R LBCL patients. Patients with relapse 12 months or more after their first-line chemoimmunotherapy (late failure: n = 25) had significantly longer overall survival (OS) than patients with refractory disease or relapse within 12 months (early failure: n = 82) (median OS: not achieved vs. 18.4 months; P < 0.001). Among patients who proceeded to autologous hematopoietic stem-cell transplantation (auto-HSCT), those with late failure had significantly longer event-free survival (EFS) than those with early failure (median EFS: 26.9 vs. 3.1 months; P = 0.012). However, no significant difference in EFS was detected among patients who underwent CAR T-cell therapy (median EFS: not reached vs. 11.8; P = 0.091). Cox regression with restricted cubic spline demonstrated that timing of relapse had significant impact on EFS in patients with auto-HSCT but not in patients with CAR T-cell therapy. Of patients who were scheduled for CAR T-cell therapy, those with late failure were significantly more likely to receive CAR T-cell therapy than those with early failure (90% vs. 57%; P = 0.008). In conclusion, patients with early failure still experienced poor outcomes after the approval of third-line CAR T-cell therapy.
Topics: Humans; Male; Female; Middle Aged; Immunotherapy, Adoptive; Aged; Lymphoma, Large B-Cell, Diffuse; Adult; Retrospective Studies; Prognosis; Hematopoietic Stem Cell Transplantation; Receptors, Chimeric Antigen; Recurrence
PubMed: 38925972
DOI: 10.3960/jslrt.24009 -
Journal For Immunotherapy of Cancer Jun 2024Despite continuous improvements in the new target and construction of chimeric antigen receptor (CAR)-T, relapse remains a significant challenge following CAR-T therapy....
BACKGROUND
Despite continuous improvements in the new target and construction of chimeric antigen receptor (CAR)-T, relapse remains a significant challenge following CAR-T therapy. Tumor microenvironment (TME) strongly correlates with the efficacy of CAR-T therapy. V-domain Ig suppressor of T-cell activation (VISTA), which exerts a multifaceted and controversial role in regulating the TME, acts not only as a ligand on antigen-presenting cells but also functions as a receptor on T cells. However, the characteristics and underlying mechanisms governing endogenous T-cell activation by VISTA, which are pivotal for reshaping the TME, remain incompletely elucidated.
METHODS
The immunocompetent B acute lymphoblastic leukemia (B-ALL), lymphoma, and melanoma murine models were employed to investigate the characteristics of endogenous T cells within the TME following CD19 and hCAIX CAR-T cell therapy, respectively. Furthermore, we examined the role of VISTA controlled by interferon (IFN)-γ signaling in regulating endogenous T-cell activation and functionality in B-ALL mice.
RESULTS
We demonstrated that the administration of CD19 CAR-T or hCAIX CAR-T cell therapy elicited augmented immune responses of endogenous T cells within the TME of B-ALL, lymphoma, and melanoma mice, thereby substantiating the efficacy of CAR-T cell efficacy. However, in the TME lacking IFN-γ signaling, VISTA levels remained elevated, resulting in attenuated cytotoxicity of endogenous T cells and reduced B-ALL recipient survival. Mice treated with CD19 CAR-T cells exhibited increased proportions of endogenous memory T cells during prolonged remission, which possessed the tumor-responsive capabilities to protect against B-ALL re-challenge. Compared with wild-type (WT) CAR-T treated mice, the administration of IFN-γ CAR-T to both WT and IFN-γ recipients resulted in a reduction in the numbers of endogenous CD4 and CD8 effectors, while exhibiting increased populations of naïve-like CD4 T and memory CD8 T cells. VISTA expression consistently remained elevated in resting or memory CD4 T cells, with distinct localization from programmed cell death protein-1 (PD-1) expressing T subsets. Blocking the VISTA signal enhanced dendritic cell-induced proliferation and cytokine production by syngeneic T cells.
CONCLUSION
Our findings confirm that endogenous T-cell activation and functionality are regulated by VISTA, which is associated with the therapeutic efficiency of CAR-T and provides a promising therapeutic strategy for relapse cases in CAR-T therapy.
Topics: Animals; Mice; Interferon-gamma; Immunotherapy, Adoptive; Antigens, CD19; Tumor Microenvironment; T-Lymphocytes; Humans; Cell Line, Tumor; Disease Models, Animal; B7 Antigens; Lymphocyte Activation; Receptors, Chimeric Antigen; Membrane Proteins
PubMed: 38925679
DOI: 10.1136/jitc-2023-008364 -
Biologicals : Journal of the... Jun 2024Convalescent plasma was proposed for passive immunization against COVID-19; but so far there are conflicting results and still open questions. However, besides...
Convalescent plasma was proposed for passive immunization against COVID-19; but so far there are conflicting results and still open questions. However, besides antibodies, other plasma proteins may be good candidates for further research and application. Thromboinflammation frequently complicates severe COVID-19, and classical anticoagulants like heparins seem to have limited effect. The natural protease inhibitors antithrombin III (ATIII), α-antitrypsin (α-AT) and α-macroglobulin (α-M), which are found decreased in severe COVD-19, play a crucial role in prothrombotic and inflammatory pathways. While ATIII and α-AT are licensed as commercially prepared therapeutic concentrates, there is no preparation of α-M available. The diagnostic, prognostic, and even therapeutic potential of plasma protease inhibitors should be further explored.
PubMed: 38924809
DOI: 10.1016/j.biologicals.2024.101781 -
The New England Journal of Medicine Jun 2024
Topics: Glioblastoma; Humans; Brain Neoplasms; T-Lymphocytes; Immunotherapy, Adoptive; Receptors, Chimeric Antigen
PubMed: 38924746
DOI: 10.1056/NEJMc2405721 -
The New England Journal of Medicine Jun 2024
Topics: Glioblastoma; Humans; Immunotherapy, Adoptive; Brain Neoplasms; T-Lymphocytes; Receptors, Chimeric Antigen; Male
PubMed: 38924745
DOI: 10.1056/NEJMc2405721 -
Cancer Medicine Jun 2024Chimeric antigen receptor T (CAR-T) cell therapy has emerged as a potent treatment for relapsed or refractory multiple myeloma, demonstrating significant clinical... (Review)
Review
BACKGROUND
Chimeric antigen receptor T (CAR-T) cell therapy has emerged as a potent treatment for relapsed or refractory multiple myeloma, demonstrating significant clinical efficacy. Despite these advances, treatment-related toxicities, particularly infections, pose a significant challenge to patient safety.
METHODS
This review synthesizes current knowledge on the mechanisms underlying post-CAR-T therapy infections, focusing on the interplay between immune dysfunction, host factors, and treatment-induced toxicity. It provides a comprehensive analysis of the temporal and individual variability in infection characteristics and the confounding clinical presentation of cytokine release syndrome.
RESULTS
The review identifies that patients receiving CAR-T cells are at increased risk of concurrent infections due to the heterogeneity in infection characteristics across different time periods, individuals, and patient groups. It highlights the diagnostic and therapeutic complexities introduced by the overlapping symptoms of infection and cytokine release syndrome.
CONCLUSION
To enhance the infection control post-CAR-T therapy, this review proposes preventive strategies tailored to the early and long-term management of patients. It underscores the need for a nuanced understanding of infection mechanisms and the importance of personalized prevention plans to improve clinical outcomes in multiple myeloma treatment.
Topics: Humans; Multiple Myeloma; Immunotherapy, Adoptive; Cytokine Release Syndrome; Receptors, Chimeric Antigen; Infections; Risk Factors
PubMed: 38923216
DOI: 10.1002/cam4.7372 -
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