Human leukocyte antigen (HLA) molecules play a predominant role in cancer immunotherapy by harnessing the immune system's capacity to differentiate between healthy and malignant cells. Most human cell types express HLA class I molecules, which interact with T-cell receptors (TCRs) to activate T cells and initiate adaptive immunological responses. The efficacy of several immunotherapeutic strategies, including checkpoint inhibitors, CAR-T-cell therapy, and personalized cancer vaccines, is significantly influenced by HLA diversity and polymorphisms. Human leukocyte antigen E (HLA-E) is a non-classical major histocompatibility complex class I (MHC-I) protein that plays a crucial role in immune regulation. Unlike classical HLA molecules, HLA-E exhibits unique immunosuppressive properties that influence tumor immune evasion mechanisms. Recent studies have highlighted the importance of HLA-E expression in various hematological malignancies and solid tumors. HLA-E interacts with inhibitory receptors on natural killer (NK) cells and certain T-cell subsets, thereby modulating immune responses against tumor cells. The expression of HLA-E on tumor cells can lead to immune escape by inhibiting the cytotoxic activity of NK and CD8+ T cells, which are critical for effective anti-tumor immunity. This review summarizes how HLA-E presents antigens, discusses recent advances in identifying HLA-E-restricted peptides, and evaluates current HLA-E-dependent and HLA-E-independent adoptive immunotherapies. Understanding the role of HLA-E in tumor immune evasion provides valuable insights for developing novel personalized cancer immunotherapies. Targeting HLA-E has the potential to increase the effectiveness of current treatments and improve patient prognosis across diverse cancer types.
Matched MeSH terms: Cancer Vaccines/therapeutic use
Certain anti-idiotypic antibodies that bind to the antigen-combining sites of antibodies can effectively mimic the three-dimensional structures and functions of the external antigens and can be used as surrogate antigens for active specific immunotherapy. Extensive studies in animal models have demonstrated the efficacy of these vaccines for triggering the immune system to induce specific and protective immunity against bacterial, viral and parasitic infections as well as tumors. Several monoclonal anti-idiotype antibodies that mimic distinct human tumor-associated antigens have been developed and characterized. Encouraging results have been obtained in recent clinical trials using these anti-idiotype antibodies as vaccines. In this article, we will review the current literature and discuss the potential of this novel therapeutic approach for various human cancers.
Matched MeSH terms: Cancer Vaccines/therapeutic use
Immunization with anti-idiotype (Id) antibodies represents a novel new approach to active immunotherapy. Extensive studies in animal tumor models have demonstrated the efficacy of anti-Id vaccines in preventing tumor growth and curing mice with established tumor. We have developed and characterized several murine monoclonal anti-Id antibodies (Ab2) which mimic distinct human tumor-associated antigens (TAA) and can be used as surrogate antigens for triggering active anti-tumor immunity in cancer patients. Encouraging results have been obtained in recent clinical trials. In this article, we will review the existing literature and summarize our own findings showing the potential of this approach for various human cancers. We will also discuss where anti-Id vaccines may perform better than traditional antigen vaccines.
Matched MeSH terms: Cancer Vaccines/therapeutic use*
Anti-idiotype (Id) vaccine therapy has been tested and shown to be effective, in several animal models, for triggering the immune system to induce specific and protective immunity against bacterial, viral and parasitic infections. The administration of anti-Id antibodies as surrogate tumor-associated antigens (TAA) also represents another potential application of the concept of the Id network. Limited experience in human trials using anti-Id to stimulate immunity against tumors has shown promising results. In this "counter-point" article, we discuss our own findings showing the potential of anti-Id antibody vaccines to be novel therapeutic approaches to various human cancers and also discuss where anti-Id vaccines may perform better than traditional multiple-epitope antigen vaccines.
Matched MeSH terms: Cancer Vaccines/therapeutic use