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Your immune system and cancer - Jonathan Cebon - BreaCan 5 August 2015

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Professor Cebon discusses the link between the immune system and cancer, immunotherapy and the current research being undertaken to develop new treatments that target cancer cells. This session was jointly hosted by BreaCan and Olivia Newton-John Cancer and Wellness Centre.

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Your immune system and cancer - Jonathan Cebon - BreaCan 5 August 2015

  1. 1. Your Immunity System & Cancer Jonathan Cebon Austin Health, Olivia Newton-John Cancer Research Institute & Olivia Newton John Cancer & Wellness Centre
  2. 2. Cancer immunosurveillance theory 1967 Tumours can be recognized and eliminated by the immune system. Macfarlane Burnet (1899–1985).
  3. 3. Melanoma in donor renal graft - 16 years after initial resection Melanoma in donor renal graft - 16 years after initial resection MacKie NEJM. 2003
  4. 4. Case 1 Mrs R • Past: Crohn’s disease – In remission 1998 • Primary melanoma diagnosed – Abdominal wall, high risk, stage IIC June 99 • 1st recurrence: skin nodules July 99 • 2nd recurrence: Brain tumour – Treated with radiotherapy
  5. 5. August 1999 Admission to hospital with Crohn’s disease flare – Spontaneous regression of – Multiple subcutaneous metastases – 3cm liver metastasis Case 1 June 1999 Feb 2000
  6. 6. Case 1 May 2001 • 3rd melanoma recurrence: R proximal humerus – Resection + prosthesis May-Jun 2001 – Vitiligo gradually developed over face, trunk, arms Dec 2001 Gall bladder surgery pigmented masses No live melanoma Melanin-laden immune cells (macrophages)
  7. 7. Case 1 • Last clinical review Jun 2014 – Alive & well – No evidence of melanoma
  8. 8. Tumor infiltrating lymphocytes: association with improved survival Melanoma
  9. 9. Summary • Stage 4 melanoma: metastatic disease in brain, liver, bone, skin, mucosal surfaces • Median survival 7 months • Spontaneous remission associated with autoimmunity Crohn’s colitis • Discussion point: can autoimmunity be harnessed as a therapeutic tool?
  10. 10. Immune Checkpoint Blockade Ribas NEJM June 2012
  11. 11. T-cell receptor: Antigen-MHC CD28: B7 CTLA-4: B7
  12. 12. Feb 2014 June 2014 Melanoma in Liver Response to Yervoy
  13. 13. Immune Checkpoint Blockade Ribas NEJM June 2012
  14. 14. LUDWIG CANCER RESEARCH September 2013 April 2014 Anti-PD-1 Malignant Melanoma Pulmonary metastases 70y M
  15. 15. Combination anti-CTLA4 & anti-PD-1 Wolchok et al June 2013
  16. 16. Slide 18 Presented By Jedd Wolchok at 2013 ASCO Annual Meeting
  17. 17. Cancer Risk following Renal Transplant ANZ Dialysis & Transplant register 1997 8618 patients Cancer Number Risk Ratio CNS Lymphoma 17 >1000 Ureter 10 250 Parathyroid 2 200 Kaposi Sarcoma 18 86 Vulva/Vagina 40 43 Penis 7 24 Cervix 65 17 Bladder 54 7 Kidney 8 7 NH Lymphoma 83 7 Liver 8 6 Colon 50 2 Breast 42 1
  18. 18. PD-1 inhibitors Active in multiple cancer types (response rates reported at June 2015) • Melanoma (17-40%) • Lung (10-30%) • Kidney (12-29%) • Bladder (25%) • Ovarian (6-23%) • Head & Neck (14-20%) • Hodgkins Lymphoma (87%) • Gastric • Triple-ve breast • Mesothelioma • HCC • Cancers with mismatch repair gene defects
  19. 19. Summary & Conclusions • Cancer responds to immune attack • Understanding the underlying science has enabled effective new therapies to be developed • Clinical trials are underway to evaluate these treatments in many different cancer types

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