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Long-term survival without graft-versus-host-disease following infusion of allogeneic myeloma-specific Vβ T cell families

Despite chemo-induction therapy and autologous stem cell transplantation (ASCT), the vast majority of patients with Multiple Myeloma (MM) relapse within 7 years and the disease remains incurable. Adoptive Allogeneic T-cell therapy (ATCT) might be curative for MM, however current ATCT protocols...


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CRISPR-Cas9 disruption of PD-1 enhances activity of universal EGFRvIII CAR T cells in a preclinical model of human glioblastoma

Despite remarkable success in the treatment of hematological malignancies, CAR T-cell therapies for solid tumors have floundered, in large part due to local immune suppression and the effects of prolonged stimulation leading to T-cell dysfunction and exhaustion. One mechanism by which gliomas...


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Guillain-Barre syndrome observed with adoptive transfer of lymphocytes genetically engineered with an NY-ESO-1 reactive T-cell receptor

Adoptive transfer of autologous T-lymphocytes transduced with a high affinity NY-ESO-1-reactive T-cell receptor (NY-ESO-1 c259 T-cells) has emerged as a promising therapeutic strategy for patients with refractory synovial sarcoma. Secondary autoimmune T-cell mediated toxicities can occur long...


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Targeting of CXCR3 improves anti-myeloma efficacy of adoptively transferred activated natural killer cells

The peculiar multiple myeloma microenvironment, characterized by up-regulated levels of several inflammatory chemokines, including the CXCR3 receptor ligands CXCL9 and CXCL10, limits NK cell positioning into the bone marrow by interfering with CXCR4 function. It is still unclear if the...


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Chronic TCR-MHC (self)-interactions limit the functional potential of TCR affinity-increased CD8 T lymphocytes

Affinity-optimized T cell receptor (TCR)-engineered lymphocytes targeting tumor antigens can mediate potent antitumor responses in cancer patients, but also bear substantial risks for off-target toxicities. Most preclinical studies have focused on T cell responses to antigen-specific stimulation...


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Systemic and local immunity following adoptive transfer of NY-ESO-1 SPEAR T cells in synovial sarcoma

Gene-modified autologous T cells expressing NY-ESO-1 c259 , an affinity-enhanced T-cell receptor (TCR) reactive against the NY-ESO-1-specific HLA-A*02-restricted peptide SLLMWITQC (NY-ESO-1 SPEAR T-cells; GSK 794), have demonstrated clinical activity in patients with advanced synovial sarcoma ...


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Inflammatory signatures for quick diagnosis of life-threatening infection during the CAR T-cell therapy

Chimeric antigen receptor-modified (CAR) T-cell immunotherapy is a novel promising therapy for treatment of B-cell malignancy. Cytokine release syndrome (CRS) and infection are the most common adverse events during CAR T-cell therapy. Similar clinical presentation of concurrent CRS and infection...


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CAR-T cell therapy: a potential new strategy against prostate cancer

Prostate cancer (PCa) is one of the main causes of cancer-related death in men. In the present immunotherapy era , several immunotherapeutic agents have been evaluated in PCa with poor results, possibly due to its low mutational burden. The recent development of chimeric antigen receptor (CAR...


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A TIGIT-based chimeric co-stimulatory switch receptor improves T-cell anti-tumor function

Tumors can employ different mechanisms to evade immune surveillance and function. Overexpression of co-inhibitory ligands that bind to checkpoint molecules on the surface of T-cells can greatly impair the function of latter. TIGIT (T cell immunoreceptor with Ig and ITIM domains) is such a co...


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Biomaterial-based platforms for in situ dendritic cell programming and their use in antitumor immunotherapy

Dendritic cells (DCs) are central players in the immune system, with an exquisite capacity to initiate and modulate immune responses. These functional characteristics have led to intense research on the development of DC-based immunotherapies, particularly for oncologic diseases. During recent...