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- Fundamental aspects
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1. Inflammation and tissue homeostasis
- Prof. Herman Waldmann
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2. Introduction to the immune system
- Prof. Herman Waldmann
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3. Hematopoiesis: the making of an immune system
- Prof. Paul J. Fairchild
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4. Inflammation: purposes, mechanisms and development
- Prof. Pietro Ghezzi
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5. Phagocytosis
- Dr. Eileen Uribe-Querol
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6. Regulated cell death mechanisms and their crosstalk with the immune system 1
- Dr. Luis Alberto Baena-Lopez
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7. Regulated cell death mechanisms and their crosstalk with the immune system 2
- Dr. Luis Alberto Baena-Lopez
- Innate immunity
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11. Cells of the innate immune system
- Prof. Kevin Maloy
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12. Microbial recognition and the immune response
- Dr. Dana Philpott
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13. Toll-like receptor signalling during infection and inflammation
- Prof. Luke O'Neill
- Intercellular mediators
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14. Chemokines
- Dr. James E. Pease
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15. Cytokines
- Prof. Iain McInnes
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16. IL-1 family cytokines as the canonical DAMPs of the immune system
- Prof. Seamus Martin
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17. Glycoimmunology
- Prof. Paula Videira
- Adaptive immunity B cells
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20. Antigen recognition in the immune system
- Prof. Herman Waldmann
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21. B cell biology
- Prof. Richard Cornall
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22. Antibody structure and function: antibody structure
- Dr. Mike Clark
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23. Antibody structure and function: antibody function
- Dr. Mike Clark
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24. Antibody genes and diversity
- Dr. Mike Clark
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25. In vivo antibody discovery and hybridoma technology
- Prof. Dr. Katja Hanack
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26. Antibody engineering: beginnings to bispecifics and beyond
- Dr. Ian Wilkinson
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28. The immunobiology of Fc receptors
- Prof. Mark Cragg
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29. Immunoreceptors
- Prof. Anton van der Merwe
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30. Affinity, avidity and kinetics in immune recognition
- Prof. Anton van der Merwe
- Adaptive immunity T cells
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31. The thymus and T cell development: a primer
- Prof. Georg Holländer
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32. Lineage decisions in the thymus: T cell lineage commitment
- Prof. Bruno Silva-Santos
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33. Lineage decisions in the thymus: αβ and γδ T cell lineages
- Prof. Bruno Silva-Santos
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34. CD4 T cell subsets
- Dr. Brigitta Stockinger
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35. Cytotoxic T lymphocytes
- Prof. Gillian Griffiths
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36. Gamma delta T-cells
- Prof. Bruno Silva-Santos
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37. Tfh and Tfr cells
- Prof. Luis Graca
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38. Tissue resident memory T cells (TRM)
- Dr. Marc Veldhoen
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39. Mathematical modeling in immunology
- Prof. Ruy M. Ribeiro
- The importance of the MHC in immunity
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40. The MHC and MHC molecules 1
- Prof. Jim Kaufman
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41. The MHC and MHC molecules 2
- Prof. Jim Kaufman
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42. Natural killer cells
- Dr. Philippa Kennedy
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44. NK cells in viral immunity
- Prof. Lewis Lanier
- Lymphocyte activation
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45. Signal transduction by leukocyte receptors
- Dr. Omer Dushek
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46. Immunological memory 1
- Prof. David Gray
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47. Immunological memory 2
- Prof. David Gray
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48. Studying immune responses “one cell at a time”
- Dr. Mir-Farzin Mashreghi
- Major cellular partners in immunity
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49. The mononuclear phagocyte system - tissue resident macrophages: distribution and functions
- Prof. Emeritus Siamon Gordon
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50. The mononuclear phagocyte system: tissue resident macrophages - activation and regulation
- Prof. Emeritus Siamon Gordon
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51. Dendritic cells: professional antigen presenting cells
- Prof. Paul J. Fairchild
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52. Mucosal immunology
- Prof. Daniel Mucida
- Immunological tolerance and regulation
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53. Self-tolerance
- Prof. Herman Waldmann
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54. Tolerance and autoimmunity
- Prof. Emerita Anne Cooke
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55. The balance between intestinal immune homeostasis and inflammation
- Prof. Dr. Janneke Samsom
- Translational immunology - immune deficiency
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56. Primary immunodeficiency disorders
- Dr. Smita Y. Patel
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57. Changes in innate and adaptive immunity during human ageing 1
- Dr. Roel De Maeyer
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58. Changes in innate and adaptive immunity during human ageing 2
- Dr. Roel De Maeyer
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59. The aging immune system
- Prof. Ana Caetano
- Translational immunology - protection against pathogenic microbes
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60. Immune responses to viruses
- Prof. Paul Klenerman
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61. HIV and the immune system
- Prof. Quentin Sattentau
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62. COVID-19: the anti-viral immune response
- Prof. Danny Altmann
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63. Bacterial immune evasion
- Prof. Christoph Tang
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64. The immunology underlying tuberculosis
- Prof. Thomas R. Hawn
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65. Innate immunity to fungi
- Prof. Gordon D. Brown
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66. Parasite immunity: introduction and Plasmodium
- Dr. Catarina Gadelha
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67. Parasite immunity: Leishmania and Schistosoma
- Dr. Catarina Gadelha
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68. Vaccination
- Dr. Anita Milicic
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69. The history of vaccines 1
- Prof. Emeritus Anthony R. Rees
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70. The history of vaccines 2
- Prof. Emeritus Anthony R. Rees
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71. The history of vaccines 3
- Prof. Emeritus Anthony R. Rees
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72. The science of vaccine adjuvants
- Dr. Derek O'Hagan
- Translational immunology - hypersensitivity, autoimmune disease and their management
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73. Hypersensitivity diseases: type 1 hypersensitivity
- Prof. Herman Waldmann
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74. Innate lymphoid cells in allergy
- Prof. Emeritus Shigeo Koyasu
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75. Hypersensitivity diseases: type II-IV hypersensitivity
- Prof. Sara Marshall
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76. B cells at the crossroads of autoimmune diseases
- Dr. Xiang Lin
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77. Interleukin-17: from clone to clinic
- Prof. Leonie Taams
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78. Autoimmunity and type 1 diabetes
- Prof. Emerita Anne Cooke
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79. What is new in type 1 diabetes?
- Prof. Åke Lernmark
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80. Antibodies to control or prevent type 1 diabetes
- Dr. Robert Hilbrands
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81. Monoclonal antibodies in haemato-oncology
- Prof. Mark Cragg
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82. Therapeutic antibodies
- Dr. Geoffrey Hale
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83. Neuroimmunometabolism
- Prof. Ana Domingos
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84. The immunology of multiple sclerosis
- Dr. Joanne Jones
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85. Understanding myasthenia gravis and advances in its management
- Prof. Henry J. Kaminski
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86. The immunology underlying rheumatic diseases
- Dr. Hussein Al-Mossawi
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88. Complement and lupus
- Prof. Marina Botto
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89. Immune mechanisms in liver diseases
- Prof. Paul Klenerman
- Translational immunology - transplantation immunology
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90. Principles of transplantation: overview of the immune response
- Prof. Emerita Kathryn Wood
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91. Factors influencing outcomes in clinical transplantation 1
- Prof. Emerita Kathryn Wood
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92. Factors influencing outcomes in clinical transplantation 2
- Prof. Emerita Kathryn Wood
- Translational immunology - cancer immunology
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93. Cancer immunology
- Prof. Tim Elliott
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94. Cancer immunotherapy
- Prof. Tim Elliott
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95. Myeloid-derived suppressor cells in cancer
- Prof. Dmitry Gabrilovich
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96. IL-2 in the immunotherapy of autoimmunity and cancer
- Prof. Thomas Malek
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97. Latest advances in the development of CAR & TCR T-cell treatments for solid tumours
- Dr. Else Marit Inderberg
Printable Handouts
Navigable Slide Index
- Introduction
- Summary
- The antibody revolution
- Currently approved mAbs for cancer
- Many antibodies are directed to the same target
- Rituximab the archetypal B-cell targeting mAb
- How do direct targeting mAb work?
- Key mediators of mAb efficacy FcγRs
- Consequences of FcγR ligation
- Dissection of mechanism
- Macrophages mediate mAb therapy via activatory FcγR
- Direct targeting mAb
- Still room for improvement
- Rituximab internalises in human cells
- Correlated with response to Rituximab in different NHL
- Internalisation correlates with FcγRIIb expression
- Current scenario with rituximab
- What is the impact of internalisation?
- Internalisation limits all 3 effector functions
- This phenomenon could cause resistance of NHL to rituximab therapy
- PFS in lymphoma patients
- How do we improve responses?
- B cell deletion as a paradigm for mAb development
- Alternative anti-CD20 mAb
- CD20 mAb depletion of circulating B cells
- Type II use the same effector mechanism
- Type II not internalised in lymphoma
- Confirmation in a mouse tumour model (EuTCL-1)
- OBZ is more than just a type II
- Impact of glyco-engineering on OBZ
- OBZ exhibits higher ADCC potency than rituximab
- Confirmation in human models
- Obinutuzumab is better BUT still requires improvement
- Tumour induces changes to the microenvironment
- Tumour extrinsic factors: Tumour alters FcγR expression
- Tumour reduces A:I ratio on macrophages
- Strategies to overcome deletion resistance
- The combination of idelalisib and rituximab
- BH3-mimetics
- Combination of OBZ with venetoclax in CLL samples
- Strategies to overcome deletion resistance
- Block FcγRIIB
- Immunomodulatory mAb
- Co-signalling interactions in T Cells
- Immunomodulatory mAbs
- What about in haematology?
- Early conclusions for immunomodulatory mAb
- Therapeutic synergy of anti-CD20 and anti-CD27 (1)
- Therapeutic synergy of anti-CD20 and anti-CD27 (2)
- Take-home messages
- Acknowledgments
Topics Covered
- Introduction to the development and clinical use of monoclonal antibodies (mAb) in haemato-oncology
- Currently approved mAb for treating cancer
- Direct targeting antibodies
- Rituximab
- Fc gamma receptors (FcgR) as key mediators of cellular immunity
- Macrophages as key effector cells
- B cell deletion as a paradigm for mAb effects
- Type I versus Type II antibodies
- Obinutuzumab
- Hematological malignancies
- Immunomodulatory mAb
- Combinations between direct targeting and immunomodulatory mAb
Links
Series:
Categories:
Therapeutic Areas:
Talk Citation
Cragg, M. (2020, May 31). Monoclonal antibodies in haemato-oncology [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved April 27, 2024, from https://hstalks.com/bs/4266/.Export Citation (RIS)
Publication History
Financial Disclosures
- Mark Cragg is a retained consultant for BioInvent International and has performed educational and advisory roles for Baxalta and Boehringer Ingleheim. He has received research funding from Roche, Gilead, Bioinvent International and GSK.
A selection of talks on Oncology
Transcript
Please wait while the transcript is being prepared...
0:00
I'm Professor Mark Cragg.
I'm a Professor of Experimental
Cancer Biology at the Center for
Cancer Immunology in Southampton.
And today,
I'm going to talk about "Monoclonal
Antibodies in Haemato- Oncology".
0:14
So as a brief introduction summary of what
I'm going to talk about today, in essence,
it's about the antibody
revolution where we've come from.
From a number of decades ago
where we had very few antibodies
in the treatment of medicine.
I'm going to give you
a case study in Rituximab,
which is the first monoclonal antibody
that's approved in haematology.
And in fact in all oncology, then I'm
going talk through some of the work that's
been done looking at the mechanisms
of action of monoclonal antibodies in
human oncology and the mechanisms of
resistance that we've now encountered.
And then, talking about some of the
strategies that we might use to try and
overcome that resistance and
that largely comes down to
using monoclonal antibodies
in various combinations.
And then, I'll have a little speculation
at the end in terms of the future and
where we're going with
some of these strategies.
1:02
So the antibody revolution really
started in the late 1990's.
In that decade really we'd got six
approved monoclonal antibodies.
Some of those were fully mouse monoclonals
and therefore had a limited utility
in humans, but
now we've got as high as over 70 approved
monoclonal antibodies that we use to
treat human beings for various diseases.
And the exciting thing is they're still
more in clinical development, and
soon to be approved.
So we have hundreds of monoclonal
antibodies in phase I and II trials and
a similar number, probably in phase III
trials that may get approved next year.
So we're looking at probably getting
to 100 in the next few years.