Th1 cytokines in pediatric acute lymphoblastic leukemia
AbstractImmune milieus play an important role in various types of cancer. The present study focuses on the effect of Th1 cytokines on pediatric acute lymphoblastic leukemia (ALL). The reaction of ALL cell lines and patient-derived xenografts (PDX) to the most important Th1 cytokines TNF- α (tumor necrosis factor alpha) and IFN-γ (interferon gamma) is analyzed and correlated with the respective cytokine receptors and the intracellular signaling molecules. ALL cell lines and ALL PDX display a great heterogeneity in cell death after incubation with TNF-α and IFN-γ. Several samples show a dose-dependent and additive induct...
Source: Cancer Immunology, Immunotherapy - October 14, 2023 Category: Cancer & Oncology Source Type: research
Dual targeting ovarian cancer by Muc16 CAR T cells secreting a bispecific T cell engager antibody for an intracellular tumor antigen WT1
AbstractEpithelial ovarian cancer is the most lethal of gynecological cancers. The therapeutic efficacy of chimeric antigen receptor (CAR) T cell directed against single antigens is limited by the heterogeneous target antigen expression in epithelial ovarian tumors. To overcome this limitation, we describe an engineered cell with both dual targeting and orthogonal cytotoxic modalities directed against two tumor antigens that are highly expressed on ovarian cancer cells: cell surface Muc16 and intracellular WT1. Muc16-specific CAR T cells (4H11) were engineered to secrete a bispecific T cell engager (BiTE) constructed from ...
Source: Cancer Immunology, Immunotherapy - October 14, 2023 Category: Cancer & Oncology Source Type: research
GK-1 effectively reduces angiogenesis and prevents T cell exhaustion in a breast cancer murine experimental model
AbstractBreast cancer is the leading malignancy in women worldwide, both in terms of incidence and mortality. Triple-negative breast cancer (TNBC) is the type with the worst clinical outcomes and with fewer therapeutic options than other types of breast cancer. GK-1 is a peptide that in the experimental model of the metastatic 4T1 breast cancer has demonstrated anti-tumor and anti-metastatic properties. Herein, GK-1 (5 mg/kg, i.v.) weekly administrated not only decreases tumor growth and the number of lung macro-metastases but also lung and lymph nodes micro-metastases. Histological analysis reveals that GK-1 reduced 57%...
Source: Cancer Immunology, Immunotherapy - October 14, 2023 Category: Cancer & Oncology Source Type: research
Cancer management during the COVID-19 world pandemic
AbstractSince 2019, the world has been experiencing an outbreak of a novel beta-coronavirus, severe acute respiratory syndrome coronavirus (SARS-CoV)-2. The worldwide spread of this virus has been a severe challenge for public health, and the World Health Organization declared the outbreak a public health emergency of international concern. As of June 8, 2023, the virus' rapid spread had caused over 767 million infections and more than 6.94 million deaths worldwide. Unlike previous SARS-CoV-1 and Middle East respiratory syndrome coronavirus outbreaks, the COVID-19 outbreak has led to a high death rate in infected patients;...
Source: Cancer Immunology, Immunotherapy - October 14, 2023 Category: Cancer & Oncology Source Type: research
Radiation-induced dormancy of intracerebral melanoma: endotoxin inflammation leads to both shortened tumor dormancy and long-term survival with localized senescence
AbstractRadiation therapy (RT) treats approximately half of all cancers and most brain cancers. RT is variably effective at inducing a dormant tumor state i.e. the time between RT and clinical recurrence of tumor growth. Interventions that significantly lengthen tumor dormancy would improve long-term outcomes. Inflammation can promote the escape of experimental tumors from metastatic dormancy in the lung. Previously we showed intracerebral B16F10 melanoma dormancy varied with RT dose; 20.5 Gy induced dormancy lasted ~ 2 to 4 weeks—sufficient time to study escape from dormancy. Tumors were followed over time using ...
Source: Cancer Immunology, Immunotherapy - October 14, 2023 Category: Cancer & Oncology Source Type: research
Intravenous injection of tumor extracellular vesicles suppresses tumor growth by reducing the regulatory T cell phenotype
ConclusionOur study suggests that TEVs possess components for tumor suppression. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - October 14, 2023 Category: Cancer & Oncology Source Type: research
Anti-CD79b/CD3 bispecific antibody combined with CAR19-T cells for B-cell lymphoma treatment
In this study, an anti-CD79b/CD3 bispecific antibody (BV28-OKT3) was constructed and combined with CAR19-T cells for B-cell lymphoma treatment. When the CD19 antigen was lost or reduced, B V28-OKT3 redirected CAR19-T cells to CD79b+ CD19– lymphoma cells; therefore, BV28-OKT3 overcomes the escape of CD79b+ CD19– lymphoma cells by the killing action of CAR19-T cells in vitro and in vivo. Furthermore, BV28-OKT3 triggered the antitumor function of CAR– T cells in the infusion product and boosted the antitumor immune response of bystander T cells, markedly improving the cytotoxicity of CAR19-T cells to lymphoma cells in v...
Source: Cancer Immunology, Immunotherapy - October 14, 2023 Category: Cancer & Oncology Source Type: research
Metabolic diversity of tumor-infiltrating T cells as target for anti-immune therapeutics
AbstractTumor-infiltrating T cells are promising drug targets to modulate the tumor microenvironment. However, tumor-infiltrating T lymphocytes, as central targets of cancer immunotherapy, show considerable heterogeneity and dynamics across tumor microenvironments and cancer types that may fundamentally influence cancer growth, metastasis, relapse, and response to clinical drugs. The T cell heterogeneity not only refers to the composition of subpopulations but also divergent metabolic states of T cells. Comparing to the diversity of tumor-infiltrating T cell compositions that have been well recognized, the metabolic divers...
Source: Cancer Immunology, Immunotherapy - October 14, 2023 Category: Cancer & Oncology Source Type: research
Reconstructing the immunosenescence core pathway reveals global characteristics in pan-cancer
In conclusion, our study provided a systematic understanding of immunosenescence pathways and revealed the global characteristics of immunosenescence in pan-cancer. We highlighted MTOR gene could be a powerful immunosenescence biomarker of HNSC that helps to develop sex-specific immunosenescence drugs. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - October 14, 2023 Category: Cancer & Oncology Source Type: research
Nomogram for predicting the prognosis of metastatic colorectal cancer patients treated with anti-PD1 therapy based on serum lipids analysis
ConclusionOverall, high level at baseline and an early elevation of HDL-C are correlated with better outcomes in mCRC patients treated with anti-PD1 therapy. The constructed nomogram indicated that the factors are strong predictive markers for response and prognosis to anti-PD-1 therapy in metastatic colorectal cancer. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - October 14, 2023 Category: Cancer & Oncology Source Type: research
Immune checkpoint inhibitor-induced neurotoxicity is not associated with seroprevalence of neurotropic infections
ConclusionPrevious viral, bacterial and protozoal neurotropic infections appear not to be associated with the development of neurological irAEs in melanoma patients who underwent therapy with ICI across 3 countries. Further efforts are needed to unravel the factors underlying neurological irAEs in order to identify risk factors for these toxicities, especially with the increasing use of ICI in earlier stage disease. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - October 14, 2023 Category: Cancer & Oncology Source Type: research
A novel agonist of 4-1BB costimulatory receptor shows therapeutic efficacy against a tobacco carcinogen-induced lung cancer
AbstractImmunotherapy utilizing checkpoint inhibitors has shown remarkable success in the treatment of cancers. In addition to immune checkpoint inhibitors, immune co-stimulation has the potential to enhance immune activation and destabilize the immunosuppressive tumor microenvironment. CD137, also known as 4-1BB, is one of the potent immune costimulatory receptors that could be targeted for effective immune co-stimulation. The interaction of the 4-1BB receptor with its natural ligand (4-1BBL) generates a strong costimulatory signal for T cell proliferation and survival. 4-1BBL lacks costimulatory activity in soluble form....
Source: Cancer Immunology, Immunotherapy - October 14, 2023 Category: Cancer & Oncology Source Type: research
A novel CD47-blocking peptide fused to pro-apoptotic KLA repeat inhibits lung cancer growth in mice
In this study, we identified a novel CD47-blocking peptide VK17 by phage display technique. A pro-apoptotic VK30 peptide was obtained after VK17 was fused to KLA amino acid repeat at C-termini. The VK30 was specifically bound to CD47 on lung cancer cells, and subsequently inducing lung cancer cell apoptosis. Meanwhile, the expression of Bax was increased, whereas the expression of Bcl-2 and Ki-67 were reduced in the VK30-treated lung cancer cells. In addition, VK30 effectively improved the phagocytic activity of macrophages against VK30-pretreated lung cancer cells. Combinational treatment of lung cancer cells with blockin...
Source: Cancer Immunology, Immunotherapy - October 13, 2023 Category: Cancer & Oncology Source Type: research
The influence of plasma sPD-L1 concentration on the effectiveness of immunotherapy in advanced NSCLC patients
ConclusionHigh sPD-L1 concentration is a negative predictor of immunotherapy efficacy in patients with NSCLC. It is worthwhile to determine sPD-L1 concentration to predict the risk of resistance to anti-PD-1 or anti-PD-L1 antibodies with greater certainty. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - October 10, 2023 Category: Cancer & Oncology Source Type: research
Translational development of a novel BAFF-R CAR-T therapy targeting B-cell lymphoid malignancies
In this study, we present the development of a novel CAR-T cell therapy targeting B-cell activating factor receptor (BAFF-R), a key regulator of B-cell proliferation and maturation. A new monoclonal antibody against BAFF-R was generated from a hybridoma clone and used to create a novel MC10029 CAR construct. Through a series of in vitro and in vivo models using the Nalm-6 cell line for leukemia and the Z138 cell line for lymphoma, we demonstrated the antigen-specific cytotoxicity of MC10029 CAR-T cells against tumor cells. Additionally, MC10029 CAR-T cells exhibited potent antitumor effects against CD19 knockout tumor cell...
Source: Cancer Immunology, Immunotherapy - October 10, 2023 Category: Cancer & Oncology Source Type: research
