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Page 1: Focal point Molecular Medicine - ruhr-uni-bochum.de · The immune response to tumors and fighting infectious diseases with vaccination Regulation of the immune system Chiara Geyer

27.06.2018 1

Focal point Molecular Medicine

http://www.brignoles.fr

Page 2: Focal point Molecular Medicine - ruhr-uni-bochum.de · The immune response to tumors and fighting infectious diseases with vaccination Regulation of the immune system Chiara Geyer

27.06.2018 2

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

vaccinated and I am proudof it!!!

What is the best cancertreatment for my friend?

Focal point Molecular Medicine

http://www.brignoles.fr

Page 3: Focal point Molecular Medicine - ruhr-uni-bochum.de · The immune response to tumors and fighting infectious diseases with vaccination Regulation of the immune system Chiara Geyer

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

Page 4: Focal point Molecular Medicine - ruhr-uni-bochum.de · The immune response to tumors and fighting infectious diseases with vaccination Regulation of the immune system Chiara Geyer

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

Page 5: Focal point Molecular Medicine - ruhr-uni-bochum.de · The immune response to tumors and fighting infectious diseases with vaccination Regulation of the immune system Chiara Geyer

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

Page 6: Focal point Molecular Medicine - ruhr-uni-bochum.de · The immune response to tumors and fighting infectious diseases with vaccination Regulation of the immune system Chiara Geyer

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

Page 7: Focal point Molecular Medicine - ruhr-uni-bochum.de · The immune response to tumors and fighting infectious diseases with vaccination Regulation of the immune system Chiara Geyer

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

Page 8: Focal point Molecular Medicine - ruhr-uni-bochum.de · The immune response to tumors and fighting infectious diseases with vaccination Regulation of the immune system Chiara Geyer

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

Page 9: Focal point Molecular Medicine - ruhr-uni-bochum.de · The immune response to tumors and fighting infectious diseases with vaccination Regulation of the immune system Chiara Geyer

• 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

Page 10: Focal point Molecular Medicine - ruhr-uni-bochum.de · The immune response to tumors and fighting infectious diseases with vaccination Regulation of the immune system Chiara Geyer

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

Page 11: Focal point Molecular Medicine - ruhr-uni-bochum.de · The immune response to tumors and fighting infectious diseases with vaccination Regulation of the immune system Chiara Geyer

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

Page 12: Focal point Molecular Medicine - ruhr-uni-bochum.de · The immune response to tumors and fighting infectious diseases with vaccination Regulation of the immune system Chiara Geyer

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

Page 13: Focal point Molecular Medicine - ruhr-uni-bochum.de · The immune response to tumors and fighting infectious diseases with vaccination Regulation of the immune system Chiara Geyer

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

Page 14: Focal point Molecular Medicine - ruhr-uni-bochum.de · The immune response to tumors and fighting infectious diseases with vaccination Regulation of the immune system Chiara Geyer

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

Page 15: Focal point Molecular Medicine - ruhr-uni-bochum.de · The immune response to tumors and fighting infectious diseases with vaccination Regulation of the immune system Chiara Geyer

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

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

Perica et al (2015)

27.06.2018 15

Page 16: Focal point Molecular Medicine - ruhr-uni-bochum.de · The immune response to tumors and fighting infectious diseases with vaccination Regulation of the immune system Chiara Geyer

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

Breast cancer:

• Breast cancer (BC) is the most common

cancer in women worldwide

• Over-expression of HER2 has been associated

with a more clinically aggressive tumor and a

worse prognosis

Romond (2005)

https://chipsahospital.org/

27.06.2018 16

Immunotherapy: Monoclonal Antibody therapy

Page 17: Focal point Molecular Medicine - ruhr-uni-bochum.de · The immune response to tumors and fighting infectious diseases with vaccination Regulation of the immune system Chiara Geyer

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

Monoclonal antibody against breast

cancer

• Monoclonal Antibody Trastuzumab

• Targets Her-2

• Combined with conventional

chemotheraphy

Maximiano et al. (2016)

27.06.2018 17

Immunotherapy: Monoclonal Antibody therapy

Page 18: Focal point Molecular Medicine - ruhr-uni-bochum.de · The immune response to tumors and fighting infectious diseases with vaccination Regulation of the immune system Chiara Geyer

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

Monoclonal antibody therapy:

• Problem with monoclonal

antibodies: inefficient killing

Janeway`s Immunobiology, 8ed (2012)

27.06.2018 18

Immunotherapy: Monoclonal Antibody therapy

Page 19: Focal point Molecular Medicine - ruhr-uni-bochum.de · The immune response to tumors and fighting infectious diseases with vaccination Regulation of the immune system Chiara Geyer

Using immune response to attack tumors

Introduction Cancer Cancer

Immunoediting Tumor specific

antigens Adoptive T-cell

immunotherapy

Monoclonal Antibodies against

tumor antigens

Checkpoint blockade

SummaryFighting infectious

diseases with vaccination

Melanoma

• malignancy of pigment-producing

cells (melanocytes)

• least common form of skin cancer, it

has the highest mortality

• median overall survival (OS) was

approximately 8 to 10 months with

approved therapies for stage IV

melanoma

McCourt (2014)

Schadendorf (2015)27.06.2018 19

Immunotherapy: Checkpoint Blockade

Page 20: Focal point Molecular Medicine - ruhr-uni-bochum.de · The immune response to tumors and fighting infectious diseases with vaccination Regulation of the immune system Chiara Geyer

Using immune response to attack tumors

Introduction Cancer Cancer

Immunoediting Tumor specific

antigens Adoptive T-cell

immunotherapy

Monoclonal Antibodies against

tumor antigens

Checkpoint blockade

SummaryFighting infectious

diseases with vaccination

Therapy against Melanoma

• Immune response is controlled by

several positive and negative

checkpoints

• Inhibitory signals such as CTLA-4

and PD-1

• Ipilimumab antagonistic monoclonal

antibody against cytotoxic T-

lymphocyte antigen-4 (CTLA-4)

Tang (2018)

27.06.2018 20

Immunotherapy: Checkpoint Blockade

Page 21: Focal point Molecular Medicine - ruhr-uni-bochum.de · The immune response to tumors and fighting infectious diseases with vaccination Regulation of the immune system Chiara Geyer

Using immune response to attack tumors

Introduction Cancer Cancer

Immunoediting Tumor specific

antigens Adoptive T-cell

immunotherapy

Monoclonal Antibodies against

tumor antigens

Checkpoint blockade

SummaryFighting infectious

diseases with vaccination

Summary

• Tumors evade or suppress the immune system in several ways

• Monoclonal antibodies have been successfully developed for tumor

immunotherapy

• Checkpoint blockade are developed to interfere with inhibitory mechanisms that

suppress the tumor response against cancer

• Current trends are attempting to incorporate immunotherapy with other

traditional anticancer drugs

27.06.2018 21

Page 22: Focal point Molecular Medicine - ruhr-uni-bochum.de · The immune response to tumors and fighting infectious diseases with vaccination Regulation of the immune system Chiara Geyer

Using immune response to attack tumors

Fighting infectious diseases with vaccination

Introduction Vaccination

Most vaccines generate antibodies

Live-attenuated viral vaccines

Peptide-based vaccines

AdjuvantsIncreasing the efficiency of

vaccinesSummary

www.hpd.de (2017)

www.hpd.de (2017)

World Helath Organisation (2018)

27.06.2018 22

Introduction: Vaccination

Page 23: Focal point Molecular Medicine - ruhr-uni-bochum.de · The immune response to tumors and fighting infectious diseases with vaccination Regulation of the immune system Chiara Geyer

https://www.sciencealert.com (2017)

Using immune response to attack tumors

Fighting infectious diseases with vaccination

Introduction Vaccination

Most vaccines generate antibodies

Live-attenuated viral vaccines

Peptide-based vaccines

AdjuvantsIncreasing the efficiency of

vaccinesSummary

27.06.2018 23

Introduction: Vaccination and

Page 24: Focal point Molecular Medicine - ruhr-uni-bochum.de · The immune response to tumors and fighting infectious diseases with vaccination Regulation of the immune system Chiara Geyer

First Vaccination

• Generation of long-lasting and protective

immunity

• Early 20th Century

• Cowpox vaccination against smallpox

• Cowpox antigens that stimulate an immune-

response that cross-reacts with smallpox

antigens

• Attenuated organisms -> stimulate

protective immunity but don´t cause disease

• Develop vaccines based on killed organisms

Riedel (2005)

https://imgur.com/gallery/oF6EQOo (2018)

Using immune response to attack tumors

Fighting infectious diseases with vaccination

Introduction Vaccination

Most vaccines generate antibodies

Live-attenuated viral vaccines

Peptide-based vaccines

AdjuvantsIncreasing the efficiency of

vaccinesSummary

27.06.2018 24

Vaccination against smallpox

Page 25: Focal point Molecular Medicine - ruhr-uni-bochum.de · The immune response to tumors and fighting infectious diseases with vaccination Regulation of the immune system Chiara Geyer

BUT: For many pathogens, natural infection does not seem to

generate protective immunity.

Riedel (2005)

Janeway`s Immunobiology, 8ed (2012)

Using immune response to attack tumors

Fighting infectious diseases with vaccination

Introduction Vaccination

Most vaccines generate antibodies

Live-attenuated viral vaccines

Peptide-based vaccines

AdjuvantsIncreasing the efficiency of

vaccinesSummary

27.06.2018 25

First Vaccination

• Generation of long-lasting and protective

immunity

• Early 20th Century

• Cowpox vaccination against smallpox

• Cowpox antigens that stimulate an immune-

response that cross-reacts with smallpox

antigens

• Attenuated organisms -> stimulate

protective immunity but don´t cause disease

• Develop vaccines based on killed organisms

Vaccination against smallpox

Page 26: Focal point Molecular Medicine - ruhr-uni-bochum.de · The immune response to tumors and fighting infectious diseases with vaccination Regulation of the immune system Chiara Geyer

Most effective vaccines generate

antibodies

• exposure to the spores of the

bacterium, Clostridium tetani

• Neurotoxins produced under

anaerobic conditions in wounds

contaminated with the bacterial

spores lead to tetanus

Antibodies:

• Prevent the damage caused by the

pathogen, prevent reinfection

• Neutralization Roitt et al. (2001)

Ganesh (2016)

Using immune response to attack tumors

Fighting infectious diseases with vaccination

Introduction Vaccination

Most vaccines generate antibodies

Live-attenuated viral vaccines

Peptide-based vaccines

AdjuvantsIncreasing the efficiency of

vaccinesSummary

27.06.2018 26

Most vaccinations generate Antibodys

Page 27: Focal point Molecular Medicine - ruhr-uni-bochum.de · The immune response to tumors and fighting infectious diseases with vaccination Regulation of the immune system Chiara Geyer

Most effective vaccines generate

antibodies

• exposure to the spores of the

bacterium, Clostridium tetani

• Neurotoxins produced under

anaerobic conditions in wounds

contaminated with the bacterial

spores lead to tetanus

Antibodies:

• Prevent the damage caused by the

pathogen, prevent reinfection

• Neutralization

Janeway`s Immunobiology, 8ed (2012)

Roitt et al. (2001)

Using immune response to attack tumors

Fighting infectious diseases with vaccination

Introduction Vaccination

Most vaccines generate antibodies

Live-attenuated viral vaccines

Peptide-based vaccines

AdjuvantsIncreasing the efficiency of

vaccinesSummary

27.06.2018 27

Most vaccinations generate Antibodys

Page 28: Focal point Molecular Medicine - ruhr-uni-bochum.de · The immune response to tumors and fighting infectious diseases with vaccination Regulation of the immune system Chiara Geyer

Safety - a big issue

• Bordetella pertussis vaccination

• Encephalitis might rarely follow

vaccination

• Two deaths after vaccination

• 13.000 cases of whooping cough

• Vaccine is no primary cause of brain

injury

Janeway`s Immunobiology, 8ed (2012)www.hpd.de (2017)

Using immune response to attack tumors

Fighting infectious diseases with vaccination

Introduction Vaccination

Most vaccines generate antibodies

Live-attenuated viral vaccines

Peptide-based vaccines

AdjuvantsIncreasing the efficiency of

vaccinesSummary

27.06.2018 28

Why is it so important that vaccines are very save?

Page 29: Focal point Molecular Medicine - ruhr-uni-bochum.de · The immune response to tumors and fighting infectious diseases with vaccination Regulation of the immune system Chiara Geyer

Generation of Live-attenuated viral vaccines

• Viruses that are treated to be unable to replicate

• Life-attenuated viral vaccines are far more potent

Janeway`s Immunobiology, 8ed (2012)

Using immune response to attack tumors

Fighting infectious diseases with vaccination

Introduction Vaccination

Most vaccines generate antibodies

Live-attenuated viral vaccines

Peptide-based vaccines

AdjuvantsIncreasing the efficiency of

vaccinesSummary

27.06.2018 29

Live-attenuated viral vaccines

Page 30: Focal point Molecular Medicine - ruhr-uni-bochum.de · The immune response to tumors and fighting infectious diseases with vaccination Regulation of the immune system Chiara Geyer

Generation of Live-attenuated viral vaccines

• Viruses that are treated to be unable to replicate

• Life-attenuated viral vaccines are far more potent

Janeway`s Immunobiology, 8ed (2012)

Using immune response to attack tumors

Fighting infectious diseases with vaccination

Introduction Vaccination

Most vaccines generate antibodies

Live-attenuated viral vaccines

Peptide-based vaccines

AdjuvantsIncreasing the efficiency of

vaccinesSummary

27.06.2018 30

Live-attenuated viral vaccines

Janeway`s Immunobiology, 8ed (2012)

Page 31: Focal point Molecular Medicine - ruhr-uni-bochum.de · The immune response to tumors and fighting infectious diseases with vaccination Regulation of the immune system Chiara Geyer

Peptide-based vaccines

• Peptide epitopes that stimulate protective immunity

• Human HLA-B53 (resistance to cerebral malaria)

• Reverse genetic analysis

• Liver stage antigen-1

Problems of peptide derived vaccines:

• Particular peptide may not bind to all MHC molecules present in

the population (highly polymorphic)

• Exogenous proteins and peptides that delivered by a synthetic

vaccine are efficiently processed for MHC II molecules but do

not enter MHC I Processing pathway

Guinovart et al. (2009)

Using immune response to attack tumors

Fighting infectious diseases with vaccination

Introduction Vaccination

Most vaccines generate antibodies

Live-attenuated viral vaccines

Peptide-based vaccines

AdjuvantsIncreasing the efficiency of

vaccinesSummary

27.06.2018 31

New development: Peptide based vaccines

Page 32: Focal point Molecular Medicine - ruhr-uni-bochum.de · The immune response to tumors and fighting infectious diseases with vaccination Regulation of the immune system Chiara Geyer

Adjuvants

• Some vaccines require additional

components to mimic how infections

normally activate innate immunity

• Adjuvants: substances that enhance the

immunogenicity of antigens (e.g. alum:

inorganic aluminum salts)

• Activation of inflammasome

• Triggering the innate immunity via TLRs

and NOD-like receptors

Spreafico (2010)

Using immune response to attack tumors

Fighting infectious diseases with vaccination

Introduction Vaccination

Most vaccines generate antibodies

Live-attenuated viral vaccines

Peptide-based vaccines

AdjuvantsIncreasing the efficiency of

vaccinesSummary

27.06.2018 32

Adjuvants and their role in vaccination

Page 33: Focal point Molecular Medicine - ruhr-uni-bochum.de · The immune response to tumors and fighting infectious diseases with vaccination Regulation of the immune system Chiara Geyer

The route of vaccination is an important determinant of success

• Ideal vaccination induces host defense at the point of entry

• Many important pathogens enter the body through mucosal

surfaces

• Live-attenuated polio-vaccine

• Three attenuated polio vaccines, highly immunogenic

• Immunity from oral poliovirus vaccine is probably lifelong

Ärzte Zeitung (2006) www.unicef.de

Nomoto (2007)

Using immune response to attack tumors

Fighting infectious diseases with vaccination

Introduction Vaccination

Most vaccines generate antibodies

Live-attenuated viral vaccines

Peptide-based vaccines

AdjuvantsIncreasing the efficiency of

vaccinesSummary

27.06.2018 33

How can the efficiency of a vaccine be improved?

Page 34: Focal point Molecular Medicine - ruhr-uni-bochum.de · The immune response to tumors and fighting infectious diseases with vaccination Regulation of the immune system Chiara Geyer

Effectiveness of a vaccine can be enhanced by targeting it to the

side of infection

• More efficient presentation can be achieved if proteolysis of the

antigen to APCs is prevented

• Target the vaccine directly to APCs

• Coat vaccine antigen with mannose

• Target vaccine antigens to selectively into the antigen-

presenting pathways of the cell (Antigen coupled to DEC

205 antibody)

Using immune response to attack tumors

Fighting infectious diseases with vaccination

Introduction Vaccination

Most vaccines generate antibodies

Live-attenuated viral vaccines

Peptide-based vaccines

AdjuvantsIncreasing the efficiency of

vaccinesSummary

27.06.2018 34

How can the efficiency of a vaccine be improved?

Page 35: Focal point Molecular Medicine - ruhr-uni-bochum.de · The immune response to tumors and fighting infectious diseases with vaccination Regulation of the immune system Chiara Geyer

Summary

• Vaccination has eradicated or virtually eliminated several human diseases (e.g. smallpox)

• There are important human infectious diseases for which there is still no effective vaccine

• Most effective vaccines are based on attenuated live microorganisms

• Vaccines can also be based on components of the microorganism or its toxin

• Vaccines based on peptides are beginning to be tested on humans

• A vaccines immunity often depends on adjuvants

• Adjuvants activate the innate immune response

Using immune response to attack tumors

Fighting infectious diseases with vaccination

Introduction Vaccination

Most vaccines generate antibodies

Live-attenuated viral vaccines

Peptide-based vaccines

AdjuvantsIncreasing the efficiency of

vaccinesSummary

27.06.2018 35

Page 36: Focal point Molecular Medicine - ruhr-uni-bochum.de · The immune response to tumors and fighting infectious diseases with vaccination Regulation of the immune system Chiara Geyer

27.06.2018 36

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

vaccinated and I am proudof it!!!

What is the best cancertreatment for my friend?

Focal point Molecular Medicine

A lot ofanswers

Thank you for your attention

Page 37: Focal point Molecular Medicine - ruhr-uni-bochum.de · The immune response to tumors and fighting infectious diseases with vaccination Regulation of the immune system Chiara Geyer

Literature (immunotherapy)

• Janeways`s Immunobiology 8th ed. Page 682-710

• Burnet FM. Oxford: Pergamon Press; 1970. Immunological surveillance

• Tang F et al. Anti-CTLA-4 antibodies in cancer immunotherapy: selective depletion of intratumoral regulatory T cells or checkpoint blockade? Cell & Bioscience. (2018);8:30. doi:10.1186/s13578-018-0229-

• Schadendorf D.,et al. Pooled Analysis of Long-Term Survival Data From Phase II and Phase III Trials of Ipilimumab in Unresectable or Metastatic Melanoma. Journal of Clinical Oncology. (2015);33(17):1889-1894. doi:10.1200/JCO.2014.56.2736.

• Romond E.H., et al. “Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer.” N Engl J Med. (2005) Oct 20;353(16):1673-84.

• Hanahan D., Weinberg R,A. “Hallmarks of cancer: the next generation.” Cell. (2011) Mar 4;144(5):646-74. doi: 10.1016/j.cell.2011.02.013.

• Maximiano S. et al. “Trastuzumab in the Treatment of Breast Cancer” BioDrugs. (2016)

• Perica K, Varela JC, Oelke M, Schneck J. Adoptive T Cell Immunotherapy for Cancer. Rambam Maimonides Medical Journal. (2015);6(1):e0004. doi:10.5041/RMMJ.10179.

• http://www.who.int/en/news-room/fact-sheets/detail/the-top-10-causes-of-death

• https://www.cdc.gov/pcd/issues/2016/16_0211.htm

• Douglas Hanahan, Robert A. Weinberg “Hallmarks of Cancer: The Next Generation” Cell. (2011) doi: 10.1016/j.cell.2011.02.013

• Karlo Perica et al. “Adoptive T Cell Immunotherapy for Cancer” (2015) Rambam Maimonides Med J. 2015 Jan; 6(1): e0004.

• Dunn et al. „The Immunobiology of Cancer Immunosurveillance and Immunoediting” Immunity (2004) doi:10.1016/j.immuni.2004.07.017

• Smyth et al. “Perforin-Mediated Cytotoxicity Is Critical for Surveillance of Spontaneous Lymphoma” JEM (2000) doi: 10.1084/jem.192.5.755

• Domenico „ The concept of immune surveillance against tumors: The first theories” Oncotarget. (2016)

Literature

Literature (vaccination)

• Janeways`s Immunobiology 8th ed. Page 682-710

• Nomoto, A. “Molecular Aspects of Poliovirus Pathogenesis.” Proceedings of the Japan Academy. Series B, Physical and Biological Sciences 83.8 (2007): 266–275. PMC. Web. 24 June 2018.

• Spreafico R, Ricciardi-Castagnoli P., Mortellaro A.” The controversial relationship between NLRP3, alum, danger signals and the next-generation adjuvants.”Eur J Immunol. (2010) Mar;40(3):638-42. doi: 10.1002/eji.200940039.

• Riedel S. Edward Jenner and the history of smallpox and vaccination. Proceedings Baylor University Medical Center. (2005);18(1):21-25.

• Ganesh M., Sheikh N.K.,Shah P., Mehetre G., Dharne M.S., Nagoba B.S., “Detection of Clostridium tetani in human clinical samples using tetX specific primers targeting the neurotoxin” Journal of Infection and Public Health(2016)doi:10.1016/j.jiph.2015.06.014

• Yang, N. J., & Chiu, I. M. (2017). Bacterial Signaling to the Nervous System via Toxins and Metabolites. Journal of Molecular Biology, 429(5), 587–605. http://doi.org/10.1016/j.jmb.2016.12.023

• Anne-Line Blankenhorn, Tania Cernuschi, Michel J. Zaffran; Exceptional Financial Support for Introduction of Inactivated Polio Vaccine in Middle-Income Countries, The Journal of Infectious Diseases, Volume 216, Issue suppl_1, 1 July 2017, Pages S52–S56, https://doi.org/10.1093/infdis/jiw573

• Clem, A. S. (2011). Fundamentals of Vaccine Immunology. Journal of Global Infectious Diseases, 3(1), 73–78. http://doi.org/10.4103/0974-777X.77299

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• Alonso, Pedro L et al. “Duration of protection with RTS,S/AS02A malaria vaccine in prevention of Plasmodium falciparum disease in Mozambican children: single-blind extended follow-up of a randomised controlled tria”l The Lancet , Volume 366 , Issue 9502 , 2012 - 2018

Using immune response to attack tumors

Fighting infectious diseases with vaccination

Introduction Vaccination

Most vaccines generate antibodies

Live-attenuated viral vaccines

Peptide-based vaccines

AdjuvantsIncreasing the efficiency of

vaccinesSummary

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