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Salmonella typhimurium:
Avoid immune-escape mechanisms
Increase visibility of the tumor site
DC
Gr
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X
X
X
X X
X
X
X
B16
TCR
Anti-Salmonella CTL
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Recombinant
attenuated
S. typhimurium
NON INVASIVE
Strain
SL3261ATK
Unable to
replicate
in vivo
AroA
AroA
InvA
108 inv+/invSalmon
Anti salmonella T cells
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C57BL/6 mice
B16
Immunotherapy approach
Vaccination:
In situ:
DC
DC+ SL GST
PBS
SL3261InvA
SL3261
100
80
80
60
60
40
40
20
20%
PBS
SL3261InvA
SL3261
100
50%
P<0,01
20
20%
10
20
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30
40
50
60
70
10
20
30
40
50
60
70
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Intra-tumor
treatment
P<0,01
Vaccinated
mice
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VHH/scFv clone
specific for tumor
antigens
U UU
U U
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pVUB4 plasmid
pVUB4 plasmid
U
Conclusions I
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S
vaccination
-7
intratumoral injections
3 weeks
135
25 29
I
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PBMC/serumm
PBMC/serum
32 36
39
I+II
43
II
46
II
1 week
53 d
Clinical Results
PI
PN
DOB
Oral Vaccination
I cycle completed
STATUS
01
F-C
13/01/1932
Completed
no
Not Immunized
02
A-L
15/09/1948
Not Done
no
03
F-G
26/04/1944
Completed
yes
PD
04
R-C
27/06/1944
Completed
no
05
G-A
11/01/1949
Completed
no
Not Immunized
06
I-F
07/11/1919
Completed
no
SD but SAE
07
A-B
28/07/1972
Completed
no
Not Immunized
08
G-D
28/02/1946
Completed
yes
PD
09
R-R
12/07/1966
Completed
no
SAE
10
A-O
04/08/1934
Completed
no
11
C-M
03/05/1964
Completed
yes
SD
12
S-A
12/03/1953
Completed
no
Not Immunized
13
A-F
26/02/1939
Completed
no
SAE
14
S-R
20/05/1953
Ongoing
no
Not evaluable
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Not Immunized
Conclusions II
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Acknowledgements
Immunotherapy Unit
Francesca Avogadri
Chiara Martinoli
Fabiana Saccheri
Paul Massa
Aida Paniccia
Erika Mileti
IEO, Milan
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Melanoma Unit
Francesco Ferrucci
Alessandro Testori
IEO, Milan