ATC Group: L03A Immunostimulants

Aldesleukin, a lymphokine, is produced by recombinant DNA technology and acts as a regulator of the immune response. The biological activities of aldesleukin and native human IL-2, a naturally occurring lymphokine, are comparable. The administration of aldesleukin in murine tumour models has been shown to reduce both tumour growth and spread. The exact mechanism by which aldesleukin-mediated immunostimulation leads to antitumour activity is not yet known.

BCG vaccine is an immunostimulating agent. It has anti-tumor activity, but the exact mechanism of action is not known.

Human granulocyte-colony stimulating factor (G-CSF) is a glycoprotein, which regulates the production and release of neutrophils from the bone marrow. Efbemalenograstim alfa is a recombinant fusion protein containing G-CSF, a 16 amino-acid linker, and the Fc portion of human IgG2. Efbemalenograstim alfa is a sustained duration form of G-CSF due to decreased renal clearance. Efbemalenograstim alfa and other G-CSFs have identical modes of action, causing a marked increase in peripheral blood neutrophil counts within 24 hours, with minor increases in monocytes and/or lymphocytes.

Eflapegrastim-xnst is a recombinant human granulocyte growth factor that binds to G-CSF receptors on myeloid progenitor cells and neutrophils, triggering signaling pathways that control cell differentiation, proliferation, migration and survival. Eflapegrastim-xnst has been shown to elevate neutrophil counts in healthy subjects and in cancer patients.

Elapegademase is a recombinant adenosine deaminase (rADA). It provides an exogenous source of ADA enzyme that is associated with a decrease in toxic adenosine and deoxyadenosine nucleotides levels as well as an increase in lymphocyte number. Severe combined immune deficiency (SCID) associated with a deficiency of ADA enzyme is a rare, inherited, and often fatal disease.

Filgrastim causes marked increases in peripheral blood neutrophil counts within 24 hours, with minor increases in monocytes.

Glatiramer is presumed to involve modulation of immune processes. Glatiramer is licensed for reduced frequency of relapses in relapsing-remitting multiple sclerosis.

Histamine/IL-2 is an immunotherapy which aims to induce immune-mediated destruction of residual myeloid leukaemic cells and thereby to prevent relapse of leukaemia. The role of histamine is to protect lymphocytes, in particular NK cells and T cells, which are responsible for the immune-mediated destruction of residual leukaemic cells.

Recombinant interferon alfa-2b is a sterile, stable, formulation of highly purified interferon alfa-2b produced by recombinant DNA techniques. Interferons exert their cellular activities by binding to specific membrane receptors on the cell surface. Recombinant interferon alfa-2b has exhibited antiproliferative effects in studies employing both animal and human cell culture systems as well as human tumour xenografts in animals. It has demonstrated significant immunomodulatory activity in vitro.

Interferon alfacon-1 is a recombinant hybrid protein based on the consensus amino acid sequence of naturally occurring human type-I interferon alphas. Interferon alfacon-1 does not act directly on the hepatitis C virus but binds to the interferon cell-surface receptor leading to the production of several interferon-stimulated gene products. Interferons induce pleiotropic biologic responses which include antiviral, antiproliferative, and immunomodulatory effects, regulation of cell surface major histocompatibility antigen (HLA class I and class II) expression and regulation of cytokine expression.

Interferon beta-1a exerts its biological effects by binding to specific receptors on the surface of human cells. This binding initiates a complex cascade of intracellular events that leads to the expression of numerous interferon-induced gene products and markers. Whether the mechanism of action of interferon beta-1a in MS is mediated by the same pathway as the biological effects described above is not known because the pathophysiology of MS is not well established.

Interferon beta-1b has been shown to possess both antiviral and immunoregulatory activity. The mechanisms by which interferon beta-1b exerts its actions in multiple sclerosis are not clearly understood. However, it is known that the biological response-modifying properties of interferon beta-1b are mediated through its interactions with specific cell receptors found on the surface of human cells.

It is presumed that interferon gamma-1b increases macrophage cytotoxicity by enhancing the respiratory burst via generation of toxic oxygen metabolites capable of mediating the killing of intracellular micro-organisms.

Leniolisib inhibits PI3K-delta by blocking the active binding site of PI3K-delta. In cell-free isolated enzyme assays, leniolisib was selective for PI3K-delta over PI3K-alpha (28-fold), PI3K-beta (43-fold), and PI3K-gamma (257-fold), as well as the broader kinome. In cell-based assays, leniolisib reduced pAkt pathway activity and inhibited proliferation and activation of B and T cell subsets.

Lenograstim belongs to the cytokine group of biologically active proteins which regulate cell differentiation and cell growth. Lenograstim induces a marked increase in peripheral blood neutrophil counts within 24 hours of administration.

Lipegfilgrastim is a sustained duration form of filgrastim due to decreased renal clearance. Lipegfilgrastim binds to human the G-CSF receptor like filgrastim and pegfilgrastim. Human G-CSF is a glycoprotein that regulates the production and release of functional neutrophils from the bone marrow.

Mifamurtide (MTP-PE) is a fully synthetic derivative of muramyl dipeptide (MDP). MTP-PE is a potent activator of monocytes and macrophages. The exact mechanism by which mifamurtide activation of monocytes and macrophages leads to anti-tumour activity in animals and humans is not yet known.

Pegfilgrastim is a sustained duration form of filgrastim due to decreased renal clearance. Pegfilgrastim and filgrastim have been shown to have identical modes of action, causing a marked increase in peripheral blood neutrophil counts within 24 hours, with minor increases in monocytes and/or lymphocytes.

Peginterferon beta-1a is an interferon conjugated to a single, linear 20 kDa methoxy poly(ethyleneglycol) molecule at the alpha-amino group of the N-terminal amino acid residue. A definitive mechanism of action of peginterferon beta-1a in multiple sclerosis (MS) is not known. Peginterferon beta-1a binds to the type I interferon receptor on the surface of cells and elicits a cascade of intracellular events leading to the regulation of interferon-responsive gene expression.

Peginterferon alpha-2a is a pegylated interferon alfa-2a that possesses the in vitro antiviral and antiproliferative activities that are characteristic of interferon alfa-2a. Peginterferon alpha-2a is indicated for the treatment of hepatitis B and C.

Peginterferon alpha-2b is a covalent conjugate of recombinant interferon alfa-2b with monomethoxy polyethylene glycol. Although the exact antiviral mode of action of recombinant interferon alfa-2b is unknown, it appears to alter the host cell metabolism. This action inhibits viral replication or if replication occurs, the progeny virions are unable to leave the cell.

Plerixafor induces leukocytosis and elevations in circulating haematopoietic progenitor cell levels due to a disruption of CXCR4 binding to its cognate ligand, known as CXCL12, resulting in the appearance of both mature and pluripotent cells in the systemic circulation. CD34+ cells mobilised by plerixafor are functional and capable of engraftment with long-term repopulating capacity.

Ropeginterferon alfa-2b is a recombinant interferon alfa-2b conjugated with a two-arm mPEG at a degree of substitution of 1 mole of polymer/mole of protein. Interferon alfa belongs to the class of type I interferons which exhibit their cellular effects by binding to a transmembrane receptor termed interferon alfa receptor (IFNAR). Binding to IFNAR initiates a downstream signalling cascade through the activation of kinases, particularly Janus kinase 1 (JAK1) and tyrosine kinase 2 (TYK2) and signal transducer and activator of transcription (STAT) proteins. Interferon alfa was shown to have an inhibitory effect on the proliferation of hematopoietic and bone marrow fibroblast progenitor cells and antagonised the action of growth factors and other cytokines that have a role in the development of myelofibrosis. These actions may be involved in the therapeutic effects of interferon alfa in polycythaemia vera.

Sargramostim is a recombinant human granulocyte-macrophage colony stimulating factor (rhu GM-CSF) produced by recombinant DNA technology in a yeast (S. cerevisiae) expression system. GM-CSF is a hematopoietic growth factor which induces partially committed progenitor cells to divide and differentiate in the granulocyte-macrophage pathways which include neutrophils, monocytes/macrophages and myeloid-derived dendritic cells.

Sipuleucel-T is an autologous cellular immunotherapy designed to induce an immune response targeted against prostatic acid phosphatase (PAP), an antigen expressed in most prostate cancers. Peripheral blood mononuclear cells collected from the patients are cultured with PAP-GM-CSF, a fusion protein consisting of PAP linked to granulocyte-macrophage colony-stimulating factor (GM-CSF) an immune cell activator. During ex vivo culture with PAP-GM-CSF, activated APCs (antigen presenting cells) take up and process the recombinant target antigen into peptides that are then presented to T cells.

Tasonermin is cytotoxic or cytostatic in vitro for a variety of tumour cell lines of different histogenesis. Tasonermin affects the morphology and reduces proliferation of endothelial cells. Also, it has profound effects on cellular components of the immune system.