Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0406810 (NAME)
 13,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To prove clinical benefits of cancer vaccine is currently difficult, except for one phase III trial has documented improved overall survival with the vaccine, Sipuleucel-T, although induction of anti-tumor immune responses through cancer vaccine is theoretically promising and would be straightforward. In contrast, immune checkpoint blockade with anti-CTLA4 mAb and anti-PD-1 mAb has demonstrated clear evidence of objective responses including improved overall survival and tumor shrinkage, driving renewed enthusiasm for cancer immunotherapy in multiple cancer types. In addition, there is a promising novel cancer immunotherapy, CAR therapy-a personalized treatment that involves genetically modifying a patient's T-cells to make them target tumor cells. We are now facing new era of cancer immunotherapy.
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PMID:Current status of cancer immunotherapy. 2507 56

Cancer immunotherapy began as a Coley's vaccine, and then, non-specific immuno- modulators, anti-tumor monoclonal antibody, cytokines, cancer vaccine (e.g. tumor antigens, dendritic cells, modified cancer cells), adoptive cell therapy (e.g. TIL, TCR/CAR-T cells), and immune-checkpoint inhibitors (PD-1/PD-Li, CTLA4 blocking antibody) have been developed and evaluated in clinical trials. The last two immunotherapies have recently shown durable clinical effects even in the patients with advanced cancers. Progress of human cancer immu- nology has been made along with the development of immunotherapy. Particularly, the anal- ysis of clinical trials of the recent immune-checkpoint inhibitors resulted in the understand- ing of human cancer immune-environments. Further investigation with multi-omics and immunological studies will lead to development of more effective cancer immunotherapy.
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PMID:Recent progress of cancer immunology and immunotherapy. 3056 49

The immune system is the hard-wired host defense mechanism against pathogens as well as cancer. Five years ago, we pondered the question if the era of cancer immunotherapy was upon us (Li et al., Exp Hem Oncol 2013). Exciting progresses have been made at all fronts since then, including (1) sweeping approval of six agents by the US Food and Drug Administration (FDA) to block the PD-1/PD-L1 pathway for treatment of 13 cancer types; (2) a paradigm shifting indication of PD-1 and CTLA4 blockers for the management of a broad class of cancers with DNA mismatch repair defect, the first-ever tissue agnostic approval of cancer drugs; (3) real world practice of adoptive T cell therapy with two CD19-directed chimeric antigen receptor T cell products (CAR-T) for relapsed and/or refractory B cell malignancies including acute lymphoid leukemia and diffuse large B cell lymphoma, signaling the birth of a field now known as synthetic immunology; (4) the award of 2018 Nobel Prize in Physiology and Medicine from the Nobel Committee to Tasuku Honjo and James Allison "for their discovery of cancer medicine by inhibition of negative immune regulation" ( www.nobelprize.org/prizes/medicine/2018 ); and (5) the emerging new concept of normalizing rather than amplifying anti-tumor immunity for guiding the next wave of revolution in the field of immuno-oncology (IO) (Sanmamed and Chen, Cell 2018).This article will highlight the significant developments of immune-oncology as of October 2018. The US FDA approved indications of all seven immune checkpoint blockers, and two CD19-directed CAR-T products are tabulated for easy references. We organized our discussion into the following sections: introduction, cell therapy, emerging immunotherapeutic strategies, expediting oncology drug development in an era of breakthrough therapies, new concepts in cancer immunology and immunotherapy, and concluding remarks. Many of these topics were covered by the 2018 China Cancer Immunotherapy Workshop in Beijing, the fourth annual conference co-organized by the Chinese American Hematologist and Oncologist Network (CAHON), China FDA (CFDA; now known as China National Medical Product Administration (NMPA)), and the Tsinghua University. We significantly expanded our discussion of important IO developments beyond what were covered in the conference, and proposed a new Three Rs conceptual framework for cancer immunotherapy, which is to reverse tolerance, rejuvenate the immune system, and restore immune homeostasis. We conclude that the future of immuno-oncology as a distinct discipline of cancer medicine has arrived.
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PMID:Recent updates in cancer immunotherapy: a comprehensive review and perspective of the 2018 China Cancer Immunotherapy Workshop in Beijing. 3057 97

The tumor microenvironmental immune cells (TMICs) consists of myeloid cells (tumor-associated macrophages, dendritic cells, myeloid-derived suppressor cells, etc.) and lymphocytes (T cells and B cells), all of which could be immunologically suppressed through their interactions with cancer cells. Immunological understanding of the tumor microenvironment (TME) has led to great success in the development of clinical cancer immunotherapeutic. The most advanced cancer immunotherapies are chimeric antigen receptor-modified T cells (CAR-T cells) and checkpoint inhibiting antibodies blocking CTLA4, PD-1 and PD-L1. However, many hurdles remain that should be addressed for improved therapeutic efficacy and reduced side effects such as cytokine release syndrome and patient-death. In recent decades, nanoparticles have been demonstrated as an efficient drug delivery tool due to their ease of modification, biocompatibility and intrinsic tumor targeting effect, and also been applied for cancer immunotherapy. In this review, we briefly introduce the immunosuppressive functions of TMICs and review recent advances in the development of TMIC-targeted nanotherapeutics for cancer immunotherapy. Tumor-associated macrophage (TAM)-targeted systems have shown to deplete or repolarize macrophages to M1 state for anti-tumoral immune responses. Tumor-infiltrating T cell (TIT)-targeted strategies have provided the activation of effector T cells and suppression of regulatory T cells in tumor, overcoming the current hurdles of single regimen checkpoint inhibitors. Lastly, recent studies on dendritic cell-targeted mRNA vaccination are discussed and the future perspectives of nano-immunotherapeutic for next-generation of cancer immunotherapy is emphasized.
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PMID:Non-viral nano-immunotherapeutics targeting tumor microenvironmental immune cells. 3139 71

The immune cells within the tumor microenvironment (TME) play important roles in tumorigenesis. It has been known that these tumor associated immune cells may possess tumor-antagonizing or tumor-promoting functions. Although the tumor-antagonizing immune cells within TME tend to target and kill the cancer cells in the early stage of tumorigenesis, the cancer cells seems to eventually escape from immune surveillance and even inhibit the cytotoxic function of tumor-antagonizing immune cells through a variety of mechanisms. The immune evasion capability, as a new hallmark of cancer, accidently provides opportunities for new strategies of cancer therapy, namely harnessing the immune cells to battle the cancer cells. Recently, the administrations of immune checkpoint modulators (represented by anti-CTLA4 and anti-PD antibodies) and adoptive immune cells (represented by CAR-T) have exhibited unexpected antitumor effect in multiple types of cancer, bringing a new era for cancer therapy. Here, we review the biological functions of immune cells within TME and their roles in cancer immunotherapy, and discuss the perspectives of the basic studies for improving the effectiveness of the clinical use.
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PMID:Immune cells within the tumor microenvironment: Biological functions and roles in cancer immunotherapy. 3173 Sep 3

The application of therapeutic T cells for a number of conditions has been developed over the past few decades with notable successes including donor lymphocyte infusions, virus-specific T cells and more recently CAR-T cell therapy. Primary immunodeficiencies are monogenetic disorders leading to abnormal development or function of the immune system. Haematopoietic stem cell transplantation and, in specific candidate diseases, haematopoietic stem cell gene therapy has been the only definitive treatment option so far. However, autologous gene-modified T cell therapy may offer a potential cure in conditions primarily affecting the lymphoid compartment. In this review we will highlight several T cell gene addition or gene-editing approaches in different target diseases with a focus on what we have learnt from clinical experience and promising preclinical studies in primary immunodeficiencies. Functional T cells are required not only for normal immune responses to infection (affected in CD40 ligand deficiency), but also for immune regulation [disrupted in IPEX syndrome (immune dysregulation, polyendocrinopathy, enteropathy, X-Linked) due to dysfunctional FOXP3 and CTLA4 deficiency] or cytotoxicity [defective in X-lymphoproliferative disease and familial haemophagocytic lymphohistiocytosis (HLH) syndromes]. In all these candidate diseases, restoration of T cell function by gene therapy could be of great value.
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PMID:T cell gene therapy to treat immunodeficiency. 3328 98