Nejvíce citovaný článek - PubMed ID 17616683
Malignant cells succumbing to some forms of radiation therapy are particularly immunogenic and hence can initiate a therapeutically relevant adaptive immune response. This reflects the intrinsic antigenicity of malignant cells (which often synthesize a high number of potentially reactive neo-antigens) coupled with the ability of radiation therapy to boost the adjuvanticity of cell death as it stimulates the release of endogenous adjuvants from dying cells. Thus, radiation therapy has been intensively investigated for its capacity to improve the therapeutic profile of several anticancer immunotherapies, including (but not limited to) checkpoint blockers, anticancer vaccines, oncolytic viruses, Toll-like receptor (TLR) agonists, cytokines, and several small molecules with immunostimulatory effects. Here, we summarize recent preclinical and clinical advances in this field of investigation.
Accumulating preclinical evidence indicates that Toll-like receptor (TLR) agonists efficiently boost tumor-targeting immune responses (re)initiated by most, if not all, paradigms of anticancer immunotherapy. Moreover, TLR agonists have been successfully employed to ameliorate the efficacy of various chemotherapeutics and targeted anticancer agents, at least in rodent tumor models. So far, only three TLR agonists have been approved by regulatory agencies for use in cancer patients. Moreover, over the past decade, the interest of scientists and clinicians in these immunostimulatory agents has been fluctuating. Here, we summarize recent advances in the preclinical and clinical development of TLR agonists for cancer therapy.
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- Ampligen™, G100, Hiltonol™, bacillus Calmette-Guérin, imiquimod, motolimod,
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The term "immunogenic cell death" (ICD) is now employed to indicate a functionally peculiar form of apoptosis that is sufficient for immunocompetent hosts to mount an adaptive immune response against dead cell-associated antigens. Several drugs have been ascribed with the ability to provoke ICD when employed as standalone therapeutic interventions. These include various chemotherapeutics routinely employed in the clinic (e.g., doxorubicin, epirubicin, idarubicin, mitoxantrone, bleomycin, bortezomib, cyclophosphamide and oxaliplatin) as well as some anticancer agents that are still under preclinical or clinical development (e.g., some microtubular inhibitors of the epothilone family). In addition, a few drugs are able to convert otherwise non-immunogenic instances of cell death into bona fide ICD, and may therefore be employed as chemotherapeutic adjuvants within combinatorial regimens. This is the case of cardiac glycosides, like digoxin and digitoxin, and zoledronic acid. Here, we discuss recent developments on anticancer chemotherapy based on ICD inducers.
- Klíčová slova
- ALL, acute lymphoblastic leukemia, AML, acute myeloid leukemia, CML, chronic myeloid leukemia, DAMP, damage-associated molecular pattern, EGFR, epidermal growth factor receptor, EOX, epirubicin plus oxaliplatin plus capecitabine, ER, endoplasmic reticulum, FDA, Food and Drug Administration, FOLFIRINOX, folinic acid plus 5-fluorouracil plus irinotecan plus oxaliplatin, FOLFOX, folinic acid plus 5-fluorouracil plus oxaliplatin, GEMOX, gemcitabine plus oxaliplatin, GM-CSF, granulocyte-macrophage colony-stimulating factor, HCC, hepatocellular carcinoma, ICD, immunogenic cell death, MM, multiple myeloma, NHL, non-Hodgkin's lymphoma, NSCLC, non-small cell lung carcinoma, TACE, transcatheter arterial chemoembolization, XELOX, capecitabine plus oxaliplatin, antigen-presenting cell, autophagy, damage-associated molecular pattern, dendritic cell, endoplasmic reticulum stress, mAb, monoclonal antibody, type I interferon,
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During the past decades, anticancer immunotherapy has evolved from a promising therapeutic option to a robust clinical reality. Many immunotherapeutic regimens are now approved by the US Food and Drug Administration and the European Medicines Agency for use in cancer patients, and many others are being investigated as standalone therapeutic interventions or combined with conventional treatments in clinical studies. Immunotherapies may be subdivided into "passive" and "active" based on their ability to engage the host immune system against cancer. Since the anticancer activity of most passive immunotherapeutics (including tumor-targeting monoclonal antibodies) also relies on the host immune system, this classification does not properly reflect the complexity of the drug-host-tumor interaction. Alternatively, anticancer immunotherapeutics can be classified according to their antigen specificity. While some immunotherapies specifically target one (or a few) defined tumor-associated antigen(s), others operate in a relatively non-specific manner and boost natural or therapy-elicited anticancer immune responses of unknown and often broad specificity. Here, we propose a critical, integrated classification of anticancer immunotherapies and discuss the clinical relevance of these approaches.
