Search results for "immunotherapy"

Immunotherapy in gastrointestinal cancer: Recent results, current studies and future perspectives

2016

The new therapeutic approach of using immune checkpoint inhibitors as anticancer agents is a landmark innovation. Early studies suggest that immune checkpoint inhibition might also be effective in patients with gastrointestinal cancer. To improve the efficacy of immunotherapy, different strategies are currently under evaluation. This review summarises the discussion during the European Organisation for Research and Treatment of Cancer Gastrointestinal Tract Cancer Translational Research Meeting in Mainz in November 2014 and provides an update on the most recent results of immune therapy in gastrointestinal cancers. Knowledge of potential relationships between tumour cells and their microenv…

Gene transfer approaches for the treatment of inflammatory bowel disease.

2003

The pathogenesis of Crohn's disease and ulcerative colitis, the two major forms of inflammatory bowel disease, involves a complex interplay between certain genetic, environmental and immunological factors. Considerable research progress in the last decade defined key inflammatory pathways in the inflamed gut and identified new potential therapeutic targets. Since the current medical treatment with corticosteroids and anti-inflammatory drugs is often associated with undesired side effects and cannot completely cure IBD, these current advances in our understanding of intestinal pathology may now allow the development of new biologic treatment strategies including gene therapy. In this review,…

A Potent Tumor-Reactive p53-Specific Single-Chain TCR without On- or Off-Target Autoimmunity In Vivo

2018

Genetic engineering of T cells with a T cell receptor (TCR) targeting tumor antigen is a promising strategy for cancer immunotherapy. Inefficient expression of the introduced TCR due to TCR mispairing may limit the efficacy and adversely affect the safety of TCR gene therapy. Here, we evaluated the safety and therapeutic efficiency of an optimized single-chain TCR (scTCR) specific for an HLA-A2.1-restricted (non-mutated) p53(264–272) peptide in adoptive T cell transfer (ACT) models using our unique transgenic mice expressing human p53 and HLA-A2.1 that closely mimic the human setting. Specifically, we showed that adoptive transfer of optimized scTCR-redirected T cells does not induce on-tar…

Strategies for tumor elimination by cytotoxic T lymphocytes.

1998

Despite differences in their tissue of origin, many tumors share high level expression of certain tumor-associated proteins. Our laboratory has focused on the possibility of utilizing antigenic components of these proteins as a focus for T-cell immunotherapy of cancer. The advantage of targeting such commonly expressed proteins is the fact that such therapy could be of value in eliminating many different types of tumors. A potential barrier in the identification of T-cell epitopes derived from these proteins and presented by tumor cells is the fact that these proteins are also expressed at low levels in some normal tissues, and therefore, self-tolerance may eliminate T cells that are capabl…

In the literature: October 2016

2016

A consortium on clinical and molecular stratification on oesophageal adenocarcinoma established in Britain has recently published in Nature Genetics , a whole-genomic sequencing analysis of more than 100 samples.1 Interestingly, they describe three distinct molecular subtypes with potential treatment relevance. This observation has also been verified in an independent validation cohort. Those three types are: (1) the ones showing homologous recombination and chromosome segregation pathways defects with enrichment of a BRCA signature. These tumours would be sensitive to DNA damaging agents, including neutron and photon irradiation with the addition of PARP inhibitors, (2) a group with high m…

FROM ALLERGEN BACK TO ANTIGEN: A RATIONAL APPROACH TO NEW FORMS OF IMMUNOTHERAPY

2007

TCR Clonality and Genomic Instability Signatures as Prognostic Biomarkers in High Grade Serous Ovarian Cancer.

2021

Simple Summary High-grade serous ovarian carcinoma (HGSC) could be analyzed with a molecular stratification defined by different genomic instability signatures associated with specific mutational process and prognostic biomarkers. Immune infiltrate is known to be a robust biomarker in HGSC. We aimed to investigate immune parameters according to genomic instability signatures. We observed that homologous recombination deficiency positive, copy cumber variant signature 7 and TCR (T cells receptor) clonality are good prognostic biomarkers in HGSC. Combining TCR clonality and genomic instability signature or T cell infiltration improved the prognostic value compared to each variable taken alone…

Physiological Mechanisms of Treatment Resistance

2009

It is generally accepted that tumor perfusion, microcirculation, characteristics of the interstitial space of tumors, oxygen (and nutrient) supply, tissue pH distribution and the bioenergetic status—factors that are usually closely linked and that define the so-called pathophysiological microenvironment—can markedly influence the therapeutic response of malignant tumors to sparsely ionizing radiation, chemotherapy, photodynamic therapy, hormonal therapy and immunotherapy. Besides more direct mechanisms involved in the development of acquired therapeutic resistance, there are in addition, obstacles in intratumor pharmacokinetics of antitumor agents due to delivery problems caused by an inade…

The Development of Vaccines from Synthetic Tumor‐Associated Mucin Glycopeptides and their Glycosylation‐Dependent Immune Response

2021

Tumor-associated carbohydrate antigens are overexpressed as altered-self in most common epithelial cancers. Their glycosylation patterns differ from those of healthy cells, functioning as an ID for cancer cells. Scientists have been developing anti-cancer vaccines based on mucin glycopeptides, yet the interplay of delivery system, adjuvant and tumor associated MUC epitopes in the induced immune response is not well understood. The current state of the art suggests that the identity, abundancy and location of the glycans on the MUC backbone are all key parameters in the cellular and humoral response. This review shares lessons learned by us in over two decades of research in glycopeptide vac…

Abstract CT020: MERIT: introducing individualized cancer vaccines for the treatment of TNBC - a phase I trial

2016

Abstract The majority of metastatic cancers remain incurable since the current methods of treatment often fail to target the heterogeneous nature of each individual patient's tumor. Personalized approaches targeting each individual patient's tumor may therefore bring significant improvements. The Mutanome Engineered RNA Immuno-Therapy (MERIT) consortium will clinically validate a pioneering RNA-based immunotherapy concept for the treatment of triple negative breast cancer (TNBC) by targeting shared tumor antigens and individual neo-antigens in TNBC patients. MERIT combines two personalized treatment concepts: (i) treatment with vaccines containing “off-the-shelf” mRNAs selected from a pre-s…