basic immunology of the mouse (and human) nicholas p. restifo, md october 19, 2015
TRANSCRIPT
Basic Immunology of the Mouse (and Human)
Nicholas P. Restifo, MD
October 19, 2015
Life started on earth about 3.5 billion years ago:mammals are a ‘recent’ development
Meet your great, great~50M-grandfather
Figure 8-1
Schematic Diagram Of The CD8 and CD4 Coreceptors
How T cell receptors, peptides and MHC molecules fit together
Schematic map of the human and mouse MHC superloci
Nomenclature of major histocompatibility complex (MHC)
Mouse
Human
Kb
Location (locus)
Strain designation
Naming MHC molecules is easy
All MHC molecules in this C57BL/6 mouse are called b
All MHC molecules in this BALB/c mouse are called d
CD8+ T cell
CD4+ T cell
Tumor cell
AntigenPresenting
Cell
TumorAntigen
What do T cells “see?”
T-cell recognition of antigens is MHC restricted
Figure 3-22
Pathways of antigen processing and presentation
TCR-peptide-MHC Crystal Structure
Figure 4-11The germline organization of the human
T-cell receptor and β loci
The numbers of human T-cell receptor gene segments and the sources of T-cell receptor diversity compared with those of immunoglobulins
Adoptive cell transfer (ACT) in mouse and man
Tumor isestablished
time
Ablate host immune system
Adoptively transfer T cells
Add vaccine and cytokine support
Tumor regression?
‘TIL’-based adoptive immunotherapy
t
t
T
Infusion of tumour-specific T cells into
patient
T Fragmentation of
tumour mass
t
Activation and selection of T cells
T cell growth factors (such as IL-2)T cell growth factors
(such as IL-2)
Add T cell growth factors (such as IL-2)
tChemotherapy+/- irradiation
Restifo, NP, et al,Nat Rev Immunol,
April, 2012
Expansion of tumour-specific T cell populations
T
Survival of patients with metastatic melanoma treated with adoptive cell transfer therapy and IL-2
93 patients treated with adoptive transfer of TIL: 9/13/2000-8/30/2009Dudley, J Clin Oncol, 2008; Rosenberg, Clin Cancer Res, 2011.
Median follow-up time 79 months (n=93)
