IMMUNOTHERAPY / IMMUNE-BASED THERAPY (IBT)
(see also Immunoprophylaxis and Immunomodulatory xenobiotics)

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Table of contents :
 
  • Active specific immunotherapy (ASI)
  • Passive immunotherapy
  • Immuno-gene therapy
  • Combined cellular and humoral immunotherapy
  • Web resources


  • The accessibility of the immune system, toegether with its central role in so many disease processes, makes it highly appropriate for therapeutic intervention.
    History of immunotherapy :
    Active specific immunotherapy (ASI)

    For modulation of Th cell responses, peptides offere several advantages over intact Ags as immunogens or tolerogens (either as altered peptide ligands (APLs), competitors, or vaccines). First, peptides require less stringent degradative conditions than native Ags. Second, with a smaller determinant, there is less likelihood of cross-reactivity between the peptide and other self-proteins. And third, peptides offer exquisite specificity over native Ags. Despite these advantages, the use of peptides has remained fairly limited, because they are rapidly cleared from the circulation and poorly taken-up by APCs (by pinocytosis only) : effectiveness of taking up can be increased by coupling peptides to ligands (eg. transferrin (Tf)) specific for cell surface receptors found on APCs (eg. CD71 / TfR).

  • Therapeutic vaccines (see also prophylactic vaccines) are used for chronic infections and cancers

  •  
    tumor model / 100-days OS
    epitopes presentable by MHC class I molecules of 
    subunit vaccines
    whole-cell vaccines
    protein Id
    DNA Id
    irradiated apoptotic cells
    irradiated apoptotic cell-loaded DCs
     
    soluble Id
    soluble Id + adjuvant (CFA, KLH)
    Id-loaded DC
    plasmid
    plasmid + GM-CSF
    fragment C (FrC) sequence from tetanus toxin
    plasmid priming + AAV boosting
    BCL1



    anti-Id antibodies-dependent 
    (30-80%)
    anti-Id antibodies-dependent (30-100%)



    38C13 (Href, Lref)

    anti-Id antibodies-independent 
    (30%)
    no anti-idiotype antibodies induced (exception : ) 
    (40%)





    no anti-Id antibodies induced 
    (80%)
    JLms (sIg-)

    CD8+ T cell-dependent 
    (20%)
    CD8+ T cell-dependent 
    (50%)





    no anti-Id antibodies induced 
    CD8+ T cell-dependent











  • immunoplacental therapy (IPT), a cancer vaccine consisting of chorionic villi extractions from the human placenta after a live full-term delivery. This therapy was first introduced in the 1970s by Valentin I. Govallo, M.D., Ph.D.ref, who noted the immunological similarities between pregnancy and cancer. The goal of cancer immunotherapy, according to Govallo, is to view the fetal allograft as an "impregnating tumor" and create an immunological state in the oncological patient analogous to a spontaneous abortion in a pregnant women. The placenta shares identical growth mechanisms, antigenic determinants, and immune-escape properties with cancer cells; this includes numerous tumor-associated antigens, angiogenic growth factors, complement regulatory proteins, and defective apoptotic mechanisms which aid in their survival. Placental vaccination may function as a multi-epitope vaccine; the body recognizes the placental antigens of this vaccine as foreign, and thus stimulates a cross reactive humoral and cell-mediated immune response targeting cancer tumor-associated antigens as well as proteins that aid in cancer angiogenesis, complement regulation, and apoptotic resistance. With recent advancements in molecular and cellular cancer immunology, the model introduced by Govallo may provide an important strategic approach to cancer immunotherapyref

  •  
  • fusogenic membrane glycoproteins (FMG), such as the vesicular stomatitis virus G glycoprotein (VSV-G), represent a new class of gene therapy for cancer that cause cytotoxic fusion on expression in tumor cells. In addition, FMG-mediated tumor cell death stimulates antitumor immunity, suggesting potential applications for FMG-expressing cellular vaccines. This study addresses the promise of FMG-expressing allogeneic tumor cells, which are most practical for clinical use, as a novel platform for ex vivo and in situ vaccination. Murine B16 melanoma-derived cell lines expressing autologous or allogeneic MHC class I, expressing fusogenic or nonfusogenic VSV-G, were used to vaccinate mice in vivo against a live tumor challenge. Exosome-like vesicles released by fusing allogeneic cells (syncitiosomes) and intratumoral injection of fusing vaccines were also tested as novel therapeutic strategies for their antitumor effects.RESULTS: Expression of fusogenic VSV-G enhanced the immunogenicity of an allogeneic cellular vaccine, which was more effective than a fusing autologous vaccine. Allogeneic syncitiosomes were only as effective as cellular vaccines when administered with adjuvant, demonstrating that syncitiosomes cannot account entirely for the mechanism of immune priming. Intratumoral injection of FMG-expressing allogeneic cells led to significant tumor regression using both fusogenic or nonfusogenic VSV-G. However, specific priming against tumor-associated antigenic epitopes and protection against secondary rechallenge only occurred if the initial vaccine was competent for cell fusion. FMG-expressing allogeneic tumor cells are a potent source of antitumor vaccines. Syncitiosomes given with adjuvant and intratumoral injection of fusing cells represent novel strategies well-suited to clinical translationref

  •  
  • transfer of ex vivo primed and/or expanded immune cells

  • Techniques : Sources :