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Carljune

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Carljune

  1. 1. Treating Cancer withPersonalized CellTherapies ThinkfestCarl H. June, MDPerelman School of Medicine PhiladelphiaUniversity of Pennsylvania December 1, 2012
  2. 2. Personalized “Precision” Therapy“Physicians consider that, when Philadelphia Chromosomethey have discovered the cause of Discovered by Peter Nowell, Penndisease, they have also discovered Pathology and Laboratory Medicinethe means of treating it.” Cicero, 106-43 B.C. Nowell and Hungerford, 1963
  3. 3. Precision Therapies: Engineered Cells• T cell therapies – what are they?• T cell therapies in clinical trials
  4. 4. Targeted Cancer Therapies- A Paradigm ShiftModern medicine, First Wave = Chemical Blockers • e.g. aspirin, penicillin and nitrogen mustard • disadvantage = side effectsSecond Wave – Biologicals = Protein Blockers • e.g. Rituxan®, for lymphoma • more natural to the body; fewer side effects • disadvantage = non-permanent and $$ expensiveThird Wave - Immunotherapies and Targeted Therapies • e.g. engineered cells expressing anti-cancer genes also “biologicals”, but permanent therapeutic • $$ cost advantage, if curative On the horizon ------ Cell Therapies!
  5. 5. General Approaches for T Cell TherapyPatient Donates Patient Input Cells (recipient-host) Host (patient) condition chemotherapy ± radiotherapy T cell transfusion Optional: genetic engineering - lentiviral vectors Expand T cells Issues - Customized (patient specific) vaccine - Blood bank model? - Market failure…
  6. 6. Health Care ChallengesChris Mason et al, Regen Med. 2011
  7. 7. Development of Clinical Scale T Cell Manufacturing Process• 1987: Discovery that CD28 is ‘gatekeeper’ for T cell proliferation Bead addition• 1993: CD3/CD28 beads first produced• 1996: First HIV patients treated Bead removal• 2001: First cancer patients treated T cell infusion
  8. 8. CART19: Chimeric Antigen Receptor T cells against CD19
  9. 9. New York Times: Overview of ApproachSeptember 2011
  10. 10. Pilot Trial Testing CD19 CARs forChemotherapy-Resistant/Refractory Leukemia: Status 12 patients Protocol ongoing: treated to date. 12 patients infused How do we treat (10 CLL; 2 ALL) 1000s? Clinical Responses: NR 3 PR 2 First Patient Dosed: 7/31/2010 CR 7
  11. 11. Generalities on First 3 treated patientsAll 3 patients had Chronic Lymphocytic Leukemia (CLL)Very late stage diseaseDisease resistant to chemotherapyMutations with bad prognosis3.5-7 pounds of tumor/patientEach infused CAR T cell killed more than 1000 tumor cells
  12. 12. Pediatric CART-19 for Acute Leukemia PI: Stephan Grupp, MD, PhD• Subject #1: 7yoF pre-B ALL• Dx May 2010: standard COG ALL• Relapse #1: 10/2011• Relapse #2: 2/2012• 3/2012: high dose cytoxan/clofaribine: persistent disease in brain, liver, spleen, kidneys, etc.• Marrow 4/16/2012: 60% blasts• CART19 4/17/2012: Dose 3.0x10^9 CD3+ cells
  13. 13. Induction of Complete Remission in Acute LeukemiaStephan Grupp
  14. 14. Pediatric Patient #1April 18, 2012 August 29, 2012 Infusion day First day of school • Status: CR (6 mo+)
  15. 15. Goals Over The Next 5 Years• FDA approval of first gene modified T cell therapies: CLL, ALL, etc• Engineered T cells for solid tumors• Robotic T cell culture: scale up
  16. 16. CARs for Cancer• Questions?

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