2/19/2018 1 F141: Advanced Melanoma: Mechanisms of Immune Therapies beyond Checkpoint blockade Delphine J. Lee, MD, PhD Chief and Program Director, Dermatology, Harbor UCLA Medical Center Principal Investigator, Los Angeles Biomedical Institute, Immunology, HUMC The Immune System and Cancer Transformed cells Normal cells Patrolling immune cells Attacking abnormal cells Successful tumor suppression Fatal Melanoma Transferred in a Donated Kidney 16 years after Melanoma Surgery » 1998: a woman died of a brain aneurysm, two kidneys were donated » That female donor had a primary melanoma 16 years before sudden death (unrelated to melanoma diagnosis 16 years earlier) » Melanoma was removed, with no residual tumor, followed in melanoma clinic for 15 years and was discharged, apparently tumor free, in 1997 NEJM 348:6. 2003
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2/19/2018
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F141: Advanced Melanoma: Mechanisms of Immune Therapies beyond Checkpoint blockade
Delphine J. Lee, MD, PhDChief and Program Director, Dermatology, Harbor UCLA Medical CenterPrincipal Investigator, Los Angeles Biomedical Institute, Immunology, HUMC
The Immune System and Cancer
Transformed cellsNormal cells
Patrolling immune cells Attacking abnormal cells
Successful tumorsuppression
Fatal Melanoma Transferred in a Donated Kidney 16 years after Melanoma Surgery
» 1998: a woman died of a brain aneurysm, two kidneys were donated
» That female donor had a primary melanoma 16 years before sudden death (unrelated to melanoma diagnosis 16 years earlier)
» Melanoma was removed, with no residual tumor, followed in melanoma clinic for 15 years and was discharged, apparently tumor free, in 1997
NEJM 348:6. 2003
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Incidence of certain cancers is higher in immune-suppressed transplant recipients
The intestinal microbiota influences the efficacy of
PD-1 blockade
Modified from Christian JobinScience 2018;359:32-34
Fecal Microbiota Transplant
• Placement of fresh or frozen stool harvested from a healthy individual into the gastrointestinal tract of the recipient
• 4th century China Ge Hong, a famous Chinese Doctor prescribed human fecal suspension by mouth for food poisoning or severe diarrhea
• 16th century China, Ming dynasty, Li ShiZhen decribedthe use of fermented, fresh or dried feces (aka “yellow soup”) to treat severe diarrhea, pain, fever, vomiting and constipation in the medical text 本草綱(纲)目(Compendium of Medical Herbs)
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Immune Modulatory Receptors
Activating InhibitingMellman et al. Nature, 2011
Blocking the InhibitingTurning up The Activating
Tumor Infiltrating Lymphocytes (TIL) or Adoptive Cell Therapy (ACT)
“Culture”
Kershaw et al. Clinical application of genetically modified T cells in cancer therapy. Clinical & Translational Immunology (2014) 3, e16; doi:10.1038/cti.2014.7
GMO T-cells
antibody‐derived binding domain
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Adoptive cell therapy with antigen‐specific T cells
Makalowski and Abken. ACT of Melanoma, DOI: 10.5772/53619
from blood
John Wayne Cancer Institute|26
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