The biology of cancer
54 min
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- Improving on "Natural" Rodent Antibodies
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26 min
1. The immunogenicity problem in antibody therapy- Prof. Herman Waldmann
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32 min
2. Antibodies by protein engineering- Prof. Sir Gregory Winter
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60 min
3. The generation of diversity in antibody genes- Prof. Michael Neuberger
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51 min
4. Innate immunity to retroelements by human AID/APOBEC3 proteins- Prof. Reuben Harris
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36 min
5. Fc receptors and antibody effector functions- Dr. Mike Clark
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57 min
6. Antibody engineering of Fc effector functions- Dr. Mike Clark
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35 min
7. Antibody engineering: beginnings to bispecifics and beyond- Dr. Ian Wilkinson
- Antibodies in Cancer Therapy
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41 min
8. Monoclonal antibodies and the ErbB system in human cancer- Prof. Mark Greene
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71 min
9. Checkpoint blockade in cancer immunotherapy- Prof. James Allison
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45 min
10. Monoclonal antibodies in haemato-oncology- Prof. Mark Cragg
- Diagnostic Antibodies
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46 min
11. Monitoring therapy with antibodies- Dr. Geoffrey Hale
- Cell Surface Glycoproteins on Cells of the Immune System
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38 min
12. Cell surface glycoproteins on cells of the immune system- Prof. Neil Barclay
- Antibodies as Immunosuppressants
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29 min
13. Monoclonal antibodies to induce therapeutic immunological tolerance- Prof. Herman Waldmann
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29 min
14. Antibodies to control or prevent type 1 diabetes- Dr. Robert Hilbrands
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48 min
15. Antibody therapy of multiple sclerosis- Dr. Alasdair Coles
- Prof. Alastair Compston
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42 min
16. Monoclonal antibodies in the management of rheumatoid arthritis- Prof. John Isaacs
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40 min
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30 min
- Archived Lectures *These may not cover the latest advances in the field
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26 min
19. Alemtuzumab (Campath-1H) in therapy of CLL- Prof. Kanti Rai
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71 min
20. VEGF inhibitors for anti-angiogenic therapy- Prof. Kari Alitalo
- Dr. Bronislaw Pytowski
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26 min
21. Human antibodies produced in mice- Dr. Marianne Bruggemann
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52 min
22. New strategies to prevent transplant rejection: from molecules to mice to monkeys to man- Prof. Christian Larsen
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55 min
23. CD20 antibodies in the targeting of B-cell malignancies and autoimmunity- Prof. Thomas Tedder
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45 min
24. Anti-IL-2 receptor antibodies as models for cancer therapy- Prof. Thomas Waldmann
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58 min
25. Anti TNF therapy in rheumatoid arthritis- Prof. Marc Feldmann
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36 min
26. Novel immunotherapeutic proteins: immunoligand- Prof. Terry Strom
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21 min
27. Diagnostic immunohistopathology- Prof. David Mason
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56 min
28. Antibodies in the control of type I diabetes- Prof. Lucienne Chatenoud
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43 min
29. The challenge of targeting toxins to tumors- Prof. Ben Seon
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38 min
30. Antibody depletion therapy in transplantation: implications for tolerance- Prof. Laurence Turka
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36 min
31. Antibodies as anti-virals- Prof. Dennis Burton
Printable Handouts
Navigable Slide Index
- Introduction
- Checkpoint blockade In cancer immunotherapy
- Two signals are required for naïve T cells activation
- Many molecules shape the immune response
- Functional asymmetry of CD28 and CTLA-4
- Integration of TCR and costimulatory signals
- Localization of CD28/CTLA-4 in migrating T cells
- The movement of CD28 and CTLA-4
- Do B7-1 or/and B7-2 dimerize?
- B7-1 may dimerizes,while B7-2 appear monomeric
- CD28 and CTLA-4 signaling complexes
- Signaling processes on the T cell - APC junction
- The role of CD28 and CTLA-4 cytoplasmic tails
- Effect of agonists' strength on CTLA-4 localization
- CD28 and CTLA- 4 trafficking
- Differential regulation of T cell responses
- CTLA-4 preferentially inhibits the best-fit response
- Models for biological role of CTLA-4
- How does CTLA-4 broaden responding repertoire?
- Biological role of CTLA-4
- Effect of CTLA-4 blockade
- Effect of anti-CTLA-4 on transplantable tumor
- Anti-CTLA-4 and GM-CSF synergise
- Side effects following rejection of B16 melanoma
- Effect of anti-CTLA-4/GVax
- CTLA-4 has a cell-autonomous activity
- Effect of exposure to anti-CTLA-4 in vivo
- Effect of exposure to anti-CTLA-4 in vitro
- Anti-CTLA-4 does not block Treg activity in vitro
- Anti-CTLA-4/GVax increases Teff/Treg ratio
- Summary: effective combinations of anti-CTLA-4
- Chimeric murine CTLA-4 transgene
- Effect of anti-CTLA-4 on MC38 tumor growth
- MDX-010 (Ipilumumab)
- Clinical response to a single dose of Ipilumumab
- MDX-010-05 study design
- Trial results: complete responder - patient 11
- Example: CTLA-4 blockade effects on tumors
- Reversible immune mediated toxicity
- MDX010-020: Pivotal Phase III Trial
- Autologous GVAX followed by MDX-010
- Trial results: melanoma patient 15
- Ovarian GVAX and Anti-CTLA-4 Ab - single dose
- Reduction in tumor nodules following MDX-010 Rx
- “Lupus-like” rash in ovarian cancer
- Ovarian GVAX and Anti-CTLA-4 Ab effects
- Research contributors
- GVAX immunotherapy and Ipilimumab for HRPC
- Trial results: PSA curves at dose-level 3
- Trial results: bone scan improvement in patient 8
- Checkpoint blockade works
- Many questions still to be answered
- Acknowledgements
- Current lab members
Topics Covered
- Activation of naive T-cells
- CD28 and CTLA-4
- Differential regulation of T-cell responses
- Responding repertoire
- Biological role of CTLA-4
- Tumor-specific immune responses
- Treg activity
- CTLA-4/GVax
- Immunotherapies
- Conventional therapies
- Ipilumumab
- Clinical studies: melanoma
- Reversible immune mediated toxicity
Links
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Therapeutic Areas:
Talk Citation
Allison, J. (2007, October 1). Checkpoint blockade in cancer immunotherapy [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved February 5, 2025, from https://doi.org/10.69645/WRFI5863.Export Citation (RIS)
Publication History
Financial Disclosures
- Prof. James Allison has not informed HSTalks of any commercial/financial relationship that it is appropriate to disclose.
Checkpoint blockade in cancer immunotherapy
Published on October 1, 2007
71 min
