-
Frontiers in Immunology 2024Triple-negative breast cancer (TNBC) is a subtype of breast cancer that presents significant therapeutic challenges due to the absence of estrogen receptor (ER),... (Review)
Review
Triple-negative breast cancer (TNBC) is a subtype of breast cancer that presents significant therapeutic challenges due to the absence of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) expression. As a result, conventional hormonal and targeted therapies are largely ineffective, underscoring the urgent need for novel treatment strategies. γδT cells, known for their robust anti-tumor properties, show considerable potential in TNBC treatment as they can identify and eliminate tumor cells without reliance on MHC restrictions. These cells demonstrate extensive proliferation both and , and can directly target tumors through cytotoxic effects or indirectly by promoting other immune responses. Studies suggest that expansion and adoptive transfer strategies targeting Vδ2 and Vδ1 γδT cell subtypes have shown promise in preclinical TNBC models. This review compiles and discusses the existing literature on the primary subgroups of γδT cells, their roles in cancer therapy, their contributions to tumor cell cytotoxicity and immune modulation, and proposes potential strategies for future γδT cell-based immunotherapies in TNBC.
Topics: Humans; Triple Negative Breast Neoplasms; Animals; Female; Receptors, Antigen, T-Cell, gamma-delta; Intraepithelial Lymphocytes; Immunotherapy, Adoptive; Immunotherapy
PubMed: 38933280
DOI: 10.3389/fimmu.2024.1420107 -
Vaccines Jun 2024The battle against Human Papillomavirus (HPV)-related cancers is hindered by suboptimal vaccination rates, despite the proven efficacy and availability of vaccines. This... (Review)
Review
The battle against Human Papillomavirus (HPV)-related cancers is hindered by suboptimal vaccination rates, despite the proven efficacy and availability of vaccines. This systematic review and meta-analysis addressed this issue by evaluating the impact of clinician communication training on increasing HPV vaccination uptake among adolescents. From an initial pool of 3213 records, six randomized controlled trials involving 245,195 participants across the United States were rigorously selected and analyzed. Our findings indicated that clinician communication training could enhance vaccination uptake rates by an average of 5.2%. Specifically, presumptive communication strategies, which proactively assume a patient's acceptance of vaccination, achieved a significant 9.1% increase in uptake, markedly outperforming the 2.3% increase observed with more passive conversational techniques. Moreover, interventions that incorporated audit and feedback processes were particularly impactful, boosting vaccination rates by 9.4%. The most striking results emerged from combining presumptive communication with audit and feedback, which propelled the effectiveness to an 11.4% increase in vaccination rates. These outcomes highlight the pivotal role of deliberate, targeted clinician-patient communication in improving health interventions. This study offers actionable insights for healthcare providers and policymakers to refine communication strategies, thus potentially maximizing HPV vaccination rates and mitigating the spread of HPV-related conditions.
PubMed: 38932340
DOI: 10.3390/vaccines12060611 -
Vaccines May 2024Hand, foot, and mouth disease (HFMD) is a contagious viral infection predominantly affecting infants and young children, caused by multiple enteroviruses, including...
Hand, foot, and mouth disease (HFMD) is a contagious viral infection predominantly affecting infants and young children, caused by multiple enteroviruses, including Enterovirus 71 (EV71), Coxsackievirus A16 (CA16), Coxsackievirus A10 (CA10), and Coxsackievirus A6 (CA6). The high pathogenicity of HFMD has garnered significant attention. Currently, there is no specific treatment or broad-spectrum preventive measure available for HFMD, and existing monovalent vaccines have limited impact on the overall incidence or prevalence of the disease. Consequently, with the emergence of new viral strains driven by vaccine pressure, there is an urgent need to develop strategies for the rapid response and control of new outbreaks. In this study, we demonstrated the broad protective effect of maternal antibodies against three types of HFMD by immunizing mother mice with a trivalent inactivated vaccine targeting EV71, CA16, and CA10, using a neonatal mouse challenge model. Based on the feasibility of maternal antibodies as a form of passive immunization to prevent HFMD, we prepared a multivalent antiviral milk by immunizing dairy cows with the trivalent inactivated vaccine to target multiple HFMD viruses. In the neonatal mouse challenge model, this immunized milk exhibited extensive passive protection against oral infections caused by the three HFMD viruses. Compared to vaccines, this strategy may offer a rapid and broadly applicable approach to providing passive immunity for the prevention of HFMD, particularly in response to the swift emergence and spread of new variants.
PubMed: 38932299
DOI: 10.3390/vaccines12060570 -
Viruses Jun 2024Although antiretroviral therapy (ART) effectively halts disease progression in HIV infection, the complete eradication of the virus remains elusive. Additionally,... (Review)
Review
BACKGROUND
Although antiretroviral therapy (ART) effectively halts disease progression in HIV infection, the complete eradication of the virus remains elusive. Additionally, challenges such as long-term ART toxicity, drug resistance, and the demanding regimen of daily and lifelong adherence required by ART highlight the imperative need for alternative therapeutic and preventative approaches. In recent years, broadly neutralizing antibodies (bNAbs) have emerged as promising candidates, offering potential for therapeutic, preventative, and possibly curative interventions against HIV infection.
OBJECTIVE
This review aims to provide a comprehensive overview of the current state of knowledge regarding the passive immunization of bNAbs in HIV-1-infected individuals.
MAIN FINDINGS
Recent findings from clinical trials have highlighted the potential of bNAbs in the treatment, prevention, and quest for an HIV-1 cure. While monotherapy with a single bNAb is insufficient in maintaining viral suppression and preventing viral escape, ultimately leading to viral rebound, combination therapy with potent, non-overlapping epitope-targeting bNAbs have demonstrated prolonged viral suppression and delayed time to rebound by effectively restricting the emergence of escape mutations, albeit largely in individuals with bNAb-sensitive strains. Additionally, passive immunization with bNAb has provided a "proof of concept" for antibody-mediated prevention against HIV-1 acquisition, although complete prevention has not been obtained. Therefore, further research on the use of bNAbs in HIV-1 treatment and prevention remains imperative.
Topics: Humans; HIV Infections; HIV-1; HIV Antibodies; Antibodies, Neutralizing; Immunization, Passive; Broadly Neutralizing Antibodies; Anti-HIV Agents; Animals
PubMed: 38932203
DOI: 10.3390/v16060911 -
International Journal of Molecular... Jun 2024CAR-T cell therapy offers a promising way for prolonged cancer remission, specifically in the case of blood cancers. However, its application in the treatment of solid... (Review)
Review
CAR-T cell therapy offers a promising way for prolonged cancer remission, specifically in the case of blood cancers. However, its application in the treatment of solid tumors still faces many limitations. This review paper provides a comprehensive overview of the challenges and strategies associated with CAR-T cell therapy for solid tumors, with a focus on gynecological cancer. This study discusses the limitations of CAR-T therapy for solid tumor treatment, such as T cell exhaustion, stromal barrier, and antigen shedding. Additionally, it addresses possible approaches to increase CAR-T efficacy in solid tumors, including combination therapies with checkpoint inhibitors and chemotherapy, as well as the novel approach of combining CAR-T with oncolytic virotherapy. Given the lack of comprehensive research on CAR-T combination therapies for treating gynecological cancers, this review aims to provide insights into the current landscape of combination therapies for solid tumors and highlight the potential of such an approach in gynecology.
Topics: Humans; Female; Genital Neoplasms, Female; Immunotherapy, Adoptive; Combined Modality Therapy; Oncolytic Virotherapy; Receptors, Chimeric Antigen; Immune Checkpoint Inhibitors; T-Lymphocytes
PubMed: 38928301
DOI: 10.3390/ijms25126595 -
International Journal of Molecular... Jun 2024Although preclinical investigations have shown notable efficacy in solid tumor models utilizing in vitro-differentiated Th17 cells for adoptive cell therapy (ACT), the...
Although preclinical investigations have shown notable efficacy in solid tumor models utilizing in vitro-differentiated Th17 cells for adoptive cell therapy (ACT), the potential benefits of this strategy in enhancing ACT efficacy in hematological malignancies, such as chronic lymphocytic leukemia (CLL), remain unexplored. CLL is a B-cell malignancy with a clinical challenge of increased resistance to targeted therapies. T-cell therapies, including chimeric antigen receptor (CAR) T cells, have demonstrated limited success in CLL, which is attributed to CLL-mediated T-cell dysfunction and skewing toward immunosuppressive phenotypes. Herein, we illustrate the feasibility of polarizing CD4 T cells from the Eμ-TCL1 murine model, the most representative model for human CLL, into Th17 phenotype, employing a protocol of T-cell activation through the inducible co-stimulator (ICOS) alongside a polarizing cytokine mixture. We demonstrate augmented memory properties of in vitro-polarized IL-17-producing T cells, and preliminary in vivo persistence in leukemia-bearing mice. Our findings gain translational relevance through successful viral transduction of Eμ-TCL1 CD4 T cells with a CD19-targeted CAR construct during in vitro Th17 polarization. Th17 CAR T cells exhibited remarkable persistence upon encountering antigen-expressing target cells. This study represents the first demonstration of the potential of in vitro-differentiated Th17 cells to enhance ACT efficacy in CLL.
Topics: Leukemia, Lymphocytic, Chronic, B-Cell; Animals; Th17 Cells; Mice; Immunotherapy, Adoptive; Humans; Lymphocyte Activation; Receptors, Chimeric Antigen; Cell Differentiation; Disease Models, Animal
PubMed: 38928031
DOI: 10.3390/ijms25126324 -
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