4
Onko (Subject) / x17 Stoitzner (Lesson)
- Which innate immune cells are involved in tumor immunity? GRANULOCYTES (neutrophils, eosinophils, basophils) MACROPHAGES MDSC (MYLOID-DERIVED SUPPRESSOR CELLS) NK CELLS DENDRITIC CELLS
- Which adaptive immune cells are involved in tumor immunity? B CELLS T CELLS in general Tregs
- Which tumor escape mechanism do you know? Failure to produce tumor antigene - lack of tumor antigenVariant of tumor cell with antigen-loss or altered antigensMutations in MHC genes or genes needed for antigen processing - no antigen prensentation production of immunesuppressive proteins and thus inhibition of T cell activation - immunosuppression
- Which immunotherapeutical approaches do you know and how do they work? • Cytokine therapy • Antibody therapy • vaccination with tumor antigen • genetic vaccines • Adoptive cell therapy: - genetically modified / killed tumor cells - tumor specific T cell transfer - dendritic cell therapy Administration of cytokines: IL-2 and Interferon - chemotherapy for treatment of melanoma and renal cell carcinoma -> activates T and NK cells for improved tumor cell killing Antibody therapy: Yervoy ® (ipilimumab) fully human anti-CTLA-4 mAb, is in Phase III trials in advanced melanoma. Yervoy may work by allowing the body’s immune system to recognize, target, and attack cells in melanoma tumors. Peptide vaccination: tumor-specific peptides (short and long) for MHC-class I and II co-administration of adjuvant is important. antigen presenting cells in tissue incorporate long peptides and process them or load short peptides directly on MHC-molecules antigen presentation in draining lymph nodes and induction of CD4+ and CD8+ T cell responses that eliminate tumor cells problem: not very efficient, combination therapy, antigen deposit at injection site genetic vaccination: plasmid DNA applied with „gene gun“ or injected intradermally, patch development for topical application delivery important: nanoparticles with lipid structure - antigen presenting cells in tissue incorporate nanoparticles, DNA integrated into cells and protein is produced and processed for antigen presentation- transport and antigen presentation in draining lymph nodes and induction of T cell responses problems: - induction of immune responses weak - Th2 responses with gene gun - nanoparticles as danger signal? immunotherapy with T cells: selection of tumor-specific T cells or transfection with tumorspecific T cell receptor, large numbers of effector cells delete tumor mass, clinical success great for transfer of T cells when lymphodepletion performed immunotherapy with NK cells • isolation and purification of NK cells from blood • expansion/activation in vitro and re-infusion into cancer patients after lymphodepletion • large numbers of effector cells delete tumor mass NK cell transfer prolongs survival in leukemia patients, inefficient so far in patients with solid tumors • problems: cells are short lived DC immunotherapy: generation of T cell-mediated anti-tumor immune responses, boost existing anti-tumor responses „Dendritic cells“ for treatment of prostate cancer monocytes are incubated with an antigen-GM-CSF conjugate for 40h and injected into patients Antigen loading: Peptide (with mature dendritic cells) - synthetic: GMP possible Protein (with immature dendritic cells) - purified - tumor lysate - apoptotic tumor cells transfection with RNA for tumor antigen (with mature dendritic cells)
Advertisement