John Maher
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View article: Prospects for Development and Commercialisation of Allogeneic CAR-Based Therapies for Autoimmune Disease
Prospects for Development and Commercialisation of Allogeneic CAR-Based Therapies for Autoimmune Disease Open
Chimeric antigen receptor (CAR)-T cell therapies represent a promising therapeutic approach for refractory autoimmune diseases. Although autologous CAR-T cells have achieved success thus far, they require expensive, individualised manufact…
View article: Lentiviral-mediated panErbB CAR-T cell therapy against head and neck squamous cell carcinomas for patients with Fanconi anemia
Lentiviral-mediated panErbB CAR-T cell therapy against head and neck squamous cell carcinomas for patients with Fanconi anemia Open
Fanconi anemia (FA) is a DNA repair syndrome characterized by bone marrow failure and cancer predisposition, including acute myeloid leukemia and solid tumors such as head and neck squamous cell carcinoma (HNSCC). Due to the exacerbated to…
View article: Glycosylated extracellular matrix drives immune suppression by controlling T cell movement, macrophage phenotype, and macrophage-T cell crosstalk in triple negative breast cancer
Glycosylated extracellular matrix drives immune suppression by controlling T cell movement, macrophage phenotype, and macrophage-T cell crosstalk in triple negative breast cancer Open
The tumor extracellular matrix (ECM) is increasingly recognized as a key driver of immune suppression and therapy resistance in cancer. However, the specific ECM components and mechanisms that create this immunosuppressive environment rema…
View article: Tumor-intrinsic interferon signaling drives pancreatic cancer resistance to tumor mucin1-targeted CAR T cell therapy
Tumor-intrinsic interferon signaling drives pancreatic cancer resistance to tumor mucin1-targeted CAR T cell therapy Open
Pancreatic cancer (PC) remains one of the most challenging cancers and has the worst prognosis. Tumor-associated MUC1 (tMUC1) is overexpressed and aberrantly glycosylated in over 80% of human pancreatic ductal adenocarcinoma (PDA). Chimeri…
View article: Harnessing the immunotherapeutic potentials of gamma delta T cells against hematological malignancies
Harnessing the immunotherapeutic potentials of gamma delta T cells against hematological malignancies Open
Gamma delta (γδ) T cells, which constitute about 5%–10% of peripheral blood lymphocytes, play key roles in tumor immunosurveillance and are often enriched within epithelial tissues. They are unique in their Major Histocompatibility Complex…
View article: Gravitational Wave Detection with Angular Deviation of Electromagnetic Waves
Gravitational Wave Detection with Angular Deviation of Electromagnetic Waves Open
In this note, we discuss interesting aspects of the interaction of electromagnetic waves (EMW) with gravitational waves (GWs) and how we can use them for GW detection. We show that there is (i) a deviation from the original path of the EMW…
View article: Neuroprotective Activity of Bromelain in Alzheimer’s Disease: an in Vitro Study on Neuroblastoma Cell Line
Neuroprotective Activity of Bromelain in Alzheimer’s Disease: an in Vitro Study on Neuroblastoma Cell Line Open
Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline, largely attributed to the accumulation of amyloid-beta (Aβ) plaques and tau tangles. Current pharmacological treatments primarily focu…
View article: Solid tumor immunotherapy using NKG2D-based adaptor CAR T cells
Solid tumor immunotherapy using NKG2D-based adaptor CAR T cells Open
NKG2D ligands (NKG2DLs) are broadly expressed in cancer. To target these, we describe an adaptor chimeric antigen receptor (CAR) termed NKG2D/Dap10-12. Herein, T cells are engineered to co-express NKG2D with a fusion protein that comprises…
View article: CAR-T cell technologies that interact with the tumour microenvironment in solid tumours
CAR-T cell technologies that interact with the tumour microenvironment in solid tumours Open
In this review, we describe a number of recent advances in CAR T-cell technology that set out to combat the problems imposed by solid tumors including tumor recruitment, infiltration, immunosuppression, metabolic compromise, and hypoxia.
View article: <i>Fusobacterium</i> is toxic for head and neck squamous cell carcinoma and its presence may determine a better prognosis
<i>Fusobacterium</i> is toxic for head and neck squamous cell carcinoma and its presence may determine a better prognosis Open
Head and neck squamous cell carcinoma (HNSCC) is a devastating disease. Despite morbid treatment, 5-year survival rates remain poor (28%-67%) [1]. There is a significant knowledge gap regarding how the microbiota may impact HNSCC treatment…
View article: Bispecific T cell engager-armed T cells targeting integrin ανβ6 exhibit enhanced T cell redirection and antitumor activity in cholangiocarcinoma
Bispecific T cell engager-armed T cells targeting integrin ανβ6 exhibit enhanced T cell redirection and antitumor activity in cholangiocarcinoma Open
Advanced cholangiocarcinoma (CCA) presents a clinical challenge due to limited treatment options, necessitating exploration of innovative therapeutic approaches. Bispecific T cell engager (BTE)-armed T cell therapy shows promise in hematol…
View article: Engineering a Dual Specificity γδ T-Cell Receptor for Cancer Immunotherapy
Engineering a Dual Specificity γδ T-Cell Receptor for Cancer Immunotherapy Open
γδ T-cells provide immune surveillance against cancer, straddling both innate and adaptive immunity. G115 is a clonal γδ T-cell receptor (TCR) of the Vγ9Vδ2 subtype which can confer responsiveness to phosphoantigens (PAgs) when genetically…
View article: Mucin-1–Targeted Chimeric Antigen Receptor T Cells Are Effective and Safe in Controlling Solid Tumors in Immunocompetent Host
Mucin-1–Targeted Chimeric Antigen Receptor T Cells Are Effective and Safe in Controlling Solid Tumors in Immunocompetent Host Open
The chimeric antigen receptor (CAR) T-cell therapy in solid epithelial tumors has been explored, however, with limited success. As much of the preclinical work has relied on xenograft models in immunocompromised animals, the immune-related…
View article: Harnessing Nanomedicine to Potentiate the Chemo-Immunotherapeutic Effects of Doxorubicin and Alendronate Co-Encapsulated in Pegylated Liposomes
Harnessing Nanomedicine to Potentiate the Chemo-Immunotherapeutic Effects of Doxorubicin and Alendronate Co-Encapsulated in Pegylated Liposomes Open
Encapsulation of Doxorubicin (Dox), a potent cytotoxic agent and immunogenic cell death inducer, in pegylated (Stealth) liposomes, is well known to have major pharmacologic advantages over treatment with free Dox. Reformulation of alendron…
View article: The Role and Regulation of the NKG2D/NKG2D Ligand System in Cancer
The Role and Regulation of the NKG2D/NKG2D Ligand System in Cancer Open
The family of human NKG2D ligands (NKG2DL) consists of eight stress-induced molecules. Over 80% of human cancers express these ligands on the surface of tumour cells and/or associated stromal elements. In mice, NKG2D deficiency increases s…
View article: Chimeric Antigen Receptor (CAR) T-Cell Therapy for Patients with Lung Cancer: Current Perspectives
Chimeric Antigen Receptor (CAR) T-Cell Therapy for Patients with Lung Cancer: Current Perspectives Open
Immunotherapy using chimeric antigen receptor (CAR)-engineered T-cells has achieved unprecedented efficacy in selected hematological cancers. However, solid tumors such as lung cancer impose several additional challenges to the attainment …
View article: Intratumoral pan-ErbB targeted CAR-T for head and neck squamous cell carcinoma: interim analysis of the T4 immunotherapy study
Intratumoral pan-ErbB targeted CAR-T for head and neck squamous cell carcinoma: interim analysis of the T4 immunotherapy study Open
Background Locally advanced/recurrent head and neck squamous cell carcinoma (HNSCC) is associated with significant morbidity and mortality. To target upregulated ErbB dimer expression in this cancer, we developed an autologous CD28-based c…
View article: Solid tumours: Building bridges to CAR‐T success
Solid tumours: Building bridges to CAR‐T success Open
Immunotherapy using chimeric antigen receptor (CAR)‐engineered T‐cells has achieved remarkable impact in the treatment of selected blood cancers. However, meaningful clinical efficacy against nonhaematological malignancies has largely prov…
View article: CAR-Based Immunotherapy of Solid Tumours—A Survey of the Emerging Targets
CAR-Based Immunotherapy of Solid Tumours—A Survey of the Emerging Targets Open
Immunotherapy with CAR T-cells has revolutionised the treatment of B-cell and plasma cell-derived cancers. However, solid tumours present a much greater challenge for treatment using CAR-engineered immune cells. In a partner review, we hav…
View article: CAR Based Immunotherapy of Solid Tumours—A Clinically Based Review of Target Antigens
CAR Based Immunotherapy of Solid Tumours—A Clinically Based Review of Target Antigens Open
Immunotherapy with CAR-engineered immune cells has transformed the management of selected haematological cancers. However, solid tumours have proven much more difficult to control using this emerging therapeutic modality. In this review, w…
View article: P06.08.B Radiation therapy enhances anti-tumor activity of a MET CAR T-based immunotherapy for glioblastoma
P06.08.B Radiation therapy enhances anti-tumor activity of a MET CAR T-based immunotherapy for glioblastoma Open
Background Glioblastoma is the most frequent primary brain tumor with dismal prognosis after standard treatment with surgery, and chemoradiation (the Stupp protocol). After a decade of failed clinical trials, tumor-treating fields have bee…
View article: Highly effective liquid and solid phase extraction methods to concentrate radioiodine isotopes for radioiodination chemistry
Highly effective liquid and solid phase extraction methods to concentrate radioiodine isotopes for radioiodination chemistry Open
Radioactive iodine isotopes play a pivotal role in radiopharmaceuticals. Large‐scale production of multi‐patient dose of radioiodinated nuclear medicines requires high concentration of radioiodine. We demonstrate that tetrabutylammonium ch…
View article: CAR T-Cell Targeting of Macrophage Colony-Stimulating Factor Receptor
CAR T-Cell Targeting of Macrophage Colony-Stimulating Factor Receptor Open
Macrophage colony-stimulating factor receptor (M-CSFR) is found in cells of the mononuclear phagocyte lineage and is aberrantly expressed in a range of tumours, in addition to tumour-associated macrophages. Consequently, a variety of cance…
View article: 3D modelling of γδ T‐cell immunotherapy
3D modelling of γδ T‐cell immunotherapy Open
Adoptive T-cell therapy has shown promise in recent years, particularly in blood cancers using autologous CAR αβ T cells that target CD19.1 However, γδ T-cell therapies have many advantages compared to their αβ T-cell counterparts. Tumour …
View article: Generation and application of TGFβ-educated human Vγ9Vδ2 T cells
Generation and application of TGFβ-educated human Vγ9Vδ2 T cells Open
Clinical trials that tested the antitumor activity of γδ T cells have been mostly unsuccessful. To address this, we expanded human Vγ9Vδ2 T cells in TGFβ1, a cytokine which enhances their viability, trafficking properties, and intrinsic an…