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Transcript of Focal point Molecular Medicine - ruhr-uni- · PDF fileThe immune response to tumors and...

  • 27.06.2018 1

    Focal point Molecular Medicine

    http://www.brignoles.fr

  • 27.06.2018 2

    I heard that vaccination is a bad thing…my son is not

    vaccinated and I am proud of it!!!

    What is the best cancer treatment for my friend?

    Focal point Molecular Medicine

    http://www.brignoles.fr

  • The immune response to tumors and fighting infectious diseases with vaccination

    Regulation of the immune system

    Chiara Geyer

    SS2018

    Using immune response to attack tumors

    Introduction Cancer Cancer

    Immunoediting Tumor specific

    antigens Adoptive T-cell

    immunotherapy

    Monoclonal Antibodies against

    tumor antigens

    Vaccination for prevention and

    therapy of cancer

    Checkpoint blockade

    Fighting infectious diseases with vaccination

    27.06.2018 3

  • Using immune response to attack tumors

    Introduction Cancer Cancer

    Immunoediting Tumor specific

    antigens Adoptive T-cell

    immunotherapy

    Monoclonal Antibodies against

    tumor antigens

    Vaccination for prevention and

    therapy of cancer

    Checkpoint blockade

    Fighting infectious diseases with vaccination

    Introduction: Cancer

    World Health Organisation (2018) Weir et al. (2016)

    27.06.2018 4

  • Introduction: Cancer

    Hanahan (2011)

    Using immune response to attack tumors

    Introduction Cancer Cancer

    Immunoediting Tumor specific

    antigens Adoptive T-cell

    immunotherapy

    Monoclonal Antibodies against

    tumor antigens

    Vaccination for prevention and

    therapy of cancer

    Checkpoint blockade

    Fighting infectious diseases with vaccination

    Lecture BCIV Schulze-Osthoff (SS 2016)

    27.06.2018 5

  • Introduction: Cancer

    Hanahan (2011)

    Using immune response to attack tumors

    Introduction Cancer Cancer

    Immunoediting Tumor specific

    antigens Adoptive T-cell

    immunotherapy

    Monoclonal Antibodies against

    tumor antigens

    Vaccination for prevention and

    therapy of cancer

    Checkpoint blockade

    Fighting infectious diseases with vaccination

    Lecture BCIV Schulze-Osthoff (SS 2016)

    27.06.2018 6

  • Immune surveillance hypothesis

    “It is by no means inconceivable that small accumulation of tumor cells may develop and because of their possession of new antigenic potentialities provoke an effective immunological reaction with regression of the tumor and no clinical hint of its existence.” (Burnet FM; 1970)

    Using immune response to attack tumors

    Introduction Cancer Cancer

    Immunoediting Tumor specific

    antigens Adoptive T-cell

    immunotherapy

    Monoclonal Antibodies against

    tumor antigens

    Vaccination for prevention and

    therapy of cancer

    Checkpoint blockade

    Fighting infectious diseases with vaccination

    27.06.2018 7

    Introduction: Cancer

  • Cancer Immunoediting

    Using immune response to attack tumors

    Introduction Cancer Cancer

    Immunoediting Tumor specific

    antigens Adoptive T-cell

    immunotherapy

    Monoclonal Antibodies against

    tumor antigens

    Vaccination for prevention and

    therapy of cancer

    Checkpoint blockade

    Fighting infectious diseases with vaccination

    Dunn et al. (2004)27.06.2018 8

  • • Mice lacking perforin show

    an increased frequency of

    lymphomas

    • Mice lacking RAG2 show

    increased rate of sarcomas

    Using immune response to attack tumors

    Introduction Cancer Cancer

    Immunoediting Tumor specific

    antigens Adoptive T-cell

    immunotherapy

    Monoclonal Antibodies against

    tumor antigens

    Vaccination for prevention and

    therapy of cancer

    Checkpoint blockade

    Fighting infectious diseases with vaccination

    Shankaran et al. (2001) Smyth et al. (2000)

    27.06.2018 9

    Cancer Immunoediting

  • Using immune response to attack tumors

    Introduction Cancer Cancer

    Immunoediting Tumor specific

    antigens Adoptive T-cell

    immunotherapy

    Monoclonal Antibodies against

    tumor antigens

    Vaccination for prevention and

    therapy of cancer

    Checkpoint blockade

    Fighting infectious diseases with vaccination

    Janeway`s Immunobiology, 8ed (2012)

    27.06.2018 10

    Cancer Immunoediting

  • Tumor specific antigens

    • Strictly tumor-specific antigens: Result from point mutations during

    oncogenesis

    • Cancer-testis antigens: Proteins encoded by genes that are normally

    expressed only in male germ cells in the testis

    • Differentiation antigens: encoded by genes that are expressed only

    in particular types of tissue

    • Strongly overexpressed antigens: derived from proteins that are

    strongly overexpressed compared to normal cells

    • Abnormal post translational modifications antigens

    • novel proteins antigens: generated when introns are retained in the

    mRNA

    • Oncoviral protein antigens: generated of viral proteins translated in

    the cell

    Using immune response to attack tumors

    Introduction Cancer Cancer

    Immunoediting Tumor specific

    antigens Adoptive T-cell

    immunotherapy

    Monoclonal Antibodies against

    tumor antigens

    Vaccination for prevention and

    therapy of cancer

    Checkpoint blockade

    Fighting infectious diseases with vaccination

    27.06.2018 11

    Anti-Cancer immune response

  • Tumor specific antigens

    • Strictly tumor-specific antigens: Result from point mutations during

    oncogenesis

    • Cancer-testis antigens: Proteins encoded by genes that are normally

    expressed only in male germ cells in the testis

    • Differentiation antigens: encoded by genes that are expressed only

    in particular types of tissue

    • Strongly overexpressed antigens: derived from proteins that are

    strongly overexpressed compared to normal cells

    • Abnormal post translational modifications antigens

    • novel proteins antigens: generated when introns are retained in the

    mRNA

    • Oncoviral protein antigens: generated of viral proteins translated in

    the cell Anti Cancer immune response

    Using immune response to attack tumors

    Introduction Cancer Cancer

    Immunoediting Tumor specific

    antigens Adoptive T-cell

    immunotherapy

    Monoclonal Antibodies against

    tumor antigens

    Vaccination for prevention and

    therapy of cancer

    Checkpoint blockade

    Fighting infectious diseases with vaccination

    Janeway`s Immunobiology, 8ed (2012)

    27.06.2018 12

    Anti-Cancer immune response

  • Tumor specific antigens

    • Strictly tumor-specific antigens: Result from point mutations during

    oncogenesis

    • Cancer-testis antigens: Proteins encoded by genes that are normally

    expressed only in male germ cells in the testis

    • Differentiation antigens: encoded by genes that are expressed only

    in particular types of tissue

    • Strongly overexpressed antigens: derived from proteins that are

    strongly overexpressed compared to normal cells

    • Abnormal post translational modifications antigens

    • novel proteins antigens: generated when introns are retained in the

    mRNA

    • Oncoviral protein antigens: generated of viral proteins translated in

    the cell

    Anti Cancer immune response

    Using immune response to attack tumors

    Introduction Cancer Cancer

    Immunoediting Tumor specific

    antigens Adoptive T-cell

    immunotherapy

    Monoclonal Antibodies against

    tumor antigens

    Vaccination for prevention and

    therapy of cancer

    Checkpoint blockade

    Fighting infectious diseases with vaccination

    27.06.2018 13

    Anti-Cancer immune response

  • Cancer Immunoediting

    Chronic myeloid leukemia (CML):

    • Bcr-Abl tyrosine kinase

    (chromosomal translocation

    t9;22)

    • HLA-A*0301 can display a

    peptide derived from the fusion

    side between Bcr-Abl

    Using immune response to attack tumors

    Introduction Cancer Cancer

    Immunoediting Tumor specific

    antigens Adoptive T-cell

    immunotherapy

    Monoclonal Antibodies against

    tumor antigens

    Vaccination for prevention and

    therapy of cancer

    Checkpoint blockade

    Fighting infectious diseases with vaccination

    27.06.2018 14

  • Immunotherapy: Adoptive T-cell therapy

    Adoptive T-cell immunotherapy:

    • T-cells specific for Bcr-Abl fusion

    protein can be identified in CML

    patients peripheral blood

    • Cytotoxic T-cells are able to

    recognize and kill the cancer cells

    Us