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The management of metastatic melanoma has been transformed by the development of immune checkpoint inhibitors. However, disease control in patients with extensive locoregional metastases remains a significant challenge. In this context, intralesional interleukin 2 (IL-2) presents a useful therapeutic option to maximize intratumoural drug concentration and minimize systemic toxicity. The utility of combined intralesional IL-2 and systemic immune checkpoint therapy, particularly in loco-regional disease, is unknown. We report the clinical and cellular effects of combined anti-programmed death-1 blockade- and intralesional IL-2 therapy in two patients with loco-regional metastatic melanoma. Combined intralesional and systemic therapy induced a lasting resolution of the injected skin tumours; maintained for up to 2 years. This impressive response was associated with increased PD-L1 expression and CD8 T cell infiltration. To our knowledge, this is the first report that raises the possibility of a synergistic effect between intralesional IL-2 and systemic checkpoint inhibition. The lasting remission of injected metastases may be in part due to an altered tumour microenvironment; characterized by increased PD-L1 expression and increased CD8 T cell infiltration. If this interesting and novel preliminary observation is confirmed in larger studies, combined local and systemic immunotherapy could highlight a novel treatment strategy for extensive loco-regional disease. This article is protected by copyright. All rights reserved.
This article was published in the following journal.
Name: Dermatologic therapy
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Keratoacanthoma (KA) is a common epidermal tumor that originates from the hair follicle of the skin. It is generally considered as a benign neoplasm, but in rare cases, it can also transform into squa...
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Substances that augment, stimulate, activate, potentiate, or modulate the immune response at either the cellular or humoral level. The classical agents (Freund's adjuvant, BCG, Corynebacterium parvum, et al.) contain bacterial antigens. Some are endogenous (e.g., histamine, interferon, transfer factor, tuftsin, interleukin-1). Their mode of action is either non-specific, resulting in increased immune responsiveness to a wide variety of antigens, or antigen-specific, i.e., affecting a restricted type of immune response to a narrow group of antigens. The therapeutic efficacy of many biological response modifiers is related to their antigen-specific immunoadjuvanticity.
A heterodimeric cytokine that plays a role in innate and adaptive immune responses. Interleukin-23 is comprised of a unique 19 kDa subunit and 40 kDa subunit that is shared with INTERLEUKIN-12. It is produced by DENDRITIC CELLS; MACROPHAGES and a variety of other immune cells
A soluble factor produced by MONOCYTES; MACROPHAGES, and other cells which activates T-lymphocytes and potentiates their response to mitogens or antigens. Interleukin-1 is a general term refers to either of the two distinct proteins, INTERLEUKIN-1ALPHA and INTERLEUKIN-1BETA. The biological effects of IL-1 include the ability to replace macrophage requirements for T-cell activation.
A receptor for INTERLEUKIN-33 that is related structurally to the interleukin-1 receptor. It contains three extracellular IMMUNOGLOBULIN-LIKE DOMAIN regions and associates with INTERLEUKIN-1 RECEPTOR ACCESSORY PROTEIN upon binding IL-33 to initiate signaling. It may function in the response of HELPER T CELLS to INFLAMMATION.
Group of diseases mediated by the deposition of large soluble complexes of antigen and antibody with resultant damage to tissue. Besides SERUM SICKNESS and the ARTHUS REACTION, evidence supports a pathogenic role for immune complexes in many other IMMUNE SYSTEM DISEASES including GLOMERULONEPHRITIS, systemic lupus erythematosus (LUPUS ERYTHEMATOSUS, SYSTEMIC) and POLYARTERITIS NODOSA.
There are three main types of skin cancer: basal cell carcinoma, squamous cell carcinoma and malignant melanoma. Basal cell carcinoma Basal cell carcinoma, or BCC, is a cancer of the basal cells at the bottom of the epidermis. It’s very common ...
Melanoma is a highly malignant tumor of melanin-forming cells (melanocytes) There are most commonly found in the skin (resulting from sunlight exposure), but also in the eyes and mucous membranes. Metastasis to other regions of the body is also common....
Clinical Approvals Clinical Trials Drug Approvals Drug Delivery Drug Discovery Generics Drugs Prescription Drugs In the fields of medicine, biotechnology and pharmacology, drug discovery is the process by which drugs are dis...