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Cytotoxic T lymphocyte antigen-4 (CTLA-4) is a negative regulator of T-cell mediated immune responses and is the target of new anti-tumor immunotherapy strategies. Ipilimumab is a fully human, antagonistic monoclonal antibody directed against CTLA-4. Results from preclinical and early clinical trials support current phase II/III testing of ipilimumab as(More)
Acute graft-versus-host disease (GVHD) results from the attack of host tissues by donor allogeneic T cells and is the most serious limitation of allogeneic hematopoietic cell transplantation (allo-HCT). Host antigen-presenting cells are thought to control the priming of alloreactive T cells and the induction of acute GVHD after allo-HCT. However, whereas(More)
The survival rate of patients diagnosed with late-stage melanoma is poor--only 5%-10%. Enlisting the immune system in the fight against cancers such as melanoma could help improve the prognosis of these patients. Data have shown that melanocyte proteins make good targets for immune system-based therapy in this disease. However, self-tolerance, which(More)
Passive immunization with monoclonal antibody TA99 targeting melanoma differentiation antigen tyrosinase-related protein-1 (Tyrp1; gp75) and active immunization with plasmid DNA encoding altered Tyrp1 both mediate tumor immunity in the B16 murine melanoma model. We report here that TA99 enhances Tyrp1 DNA vaccination in the treatment of B16 lung metastases,(More)
Talimogene laherparepvec (T-Vec) is the first live virus to be approved by the US Food and Drug Administration for the treatment of cancer. This engineered version of herpes simplex virus type 1 (HSV-1) is the product of decades of preclinical work aimed at identifying and modifying aspects of the viral genome involved in virulence and immunogenicity. T-Vec(More)
BACKGROUND & AIMS Premalignant lesions and early stage tumors contain immunosuppressive microenvironments that create barriers for cancer vaccines. Kras(G12D/+);Trp53(R172H/+);Pdx-1-Cre (KPC) mice, which express an activated form of Kras in pancreatic tissues, develop pancreatic intraepithelial neoplasms (PanIN) that progress to pancreatic ductal(More)
The structure recognized by regulatory T cells that enables them to discriminate self from nonself in the periphery is one of the central issues of regulatory T cell biology. A link between immunoregulation and self-nonself discrimination has emerged from experiments showing that Qa-1-restricted CD8(+) T cells selectively down-regulate target T cells(More)
Patients with resected stage II-III cutaneous melanomas remain at high risk for metastasis and death. Biomarker development has been limited by the challenge of isolating high-quality RNA for transcriptome-wide profiling from formalin-fixed and paraffin-embedded (FFPE) primary tumor specimens. Using NanoString technology, RNA from 40 stage II-III FFPE(More)
Matrix metalloproteinase-2 (MMP-2) is involved in several physiological mechanisms, including wound healing and tumor progression. We show that MMP-2 directly stimulates dendritic cells (DCs) to both upregulate OX40L on the cell surface and secrete inflammatory cytokines. The mechanism underlying DC activation includes physical association with Toll-like(More)
BACKGROUND To date, patients with pre-existing autoimmune conditions have been excluded from immunotherapy trials out of concern for severe autoimmune exacerbations. CASE PRESENTATION We describe the first case of a patient with metastatic cKIT mutated acral melanoma, brain metastasis, and pre-existing severe autoimmune bullous pemphigoid (BP) with stable(More)