Dr Sujit Chatterjee Hiranandani Hospital Kidney.pdf
Dr Alessandro Perra , Guna S,p.a.Italy
1. Future Health Summit
LOW DOSE CYTOKINES IN SUPPORTIVE THERAPY FOR CANCER
From research: Up to date pre-clinical evidence
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DUBLIN
May 26th, 2016
Alessandro Perra – Scientific Director of GUNA S.p.a.
18. Raphael I et al. T cell subsets and their signature cytokines in autoimmune and inflammatory diseases. Cytokine (2014),
http://dx.doi.org/10.1016/j.cyto.2014.09.011
Neither good nor bad in Nature
32. EX VIVO STUDY
16 subjects
(10 males, 6 females; mean age 73; range 57-83)
With colon carcinoma
16
9 primary colon
carcinoma
2 Dukes A
7 Dukes B 1-2
7 metastatic colon
carcinoma
Dukes C 1-2
with lymph
node
metastasis
12 subjects
(7 males, 5 females; mean age 64; range 37-85)
Healthy donors
33. EX VIVO STUDY
INCLUSION CRITERIA
• Subjects affected by primary colon carcinoma needing surgery without
pre-surgery evidence of distance metatstasis a
PREPARATIONS
• SKA-IL-4 (10 fg/ml) GUNA Laboratories
• SKA-IL-12 (10 fg/ml) GUNA Laboratories
• rhIL-4 (1ng/ml) Pepro Tech Inc.
• rhIL-12 (1ng/ml) Pepro Tech Inc.
34. Translational Oncology 2015 8, 327-338DOI: (10.1016/j.tranon.2015.06.005)
(A) MoDC (monocyte derived denditic cells) allostimulatory
activity of colon carcinoma patients (n = 16) versus
healthy donors (n = 12). (B) MoDC allostimulatory
activity of nonmetastatic (n = 9) versus metastatic (n
= 7) colon carcinoma patients. MoDCs, generated by
culturing PB CD14+
cells from tumor and normal
subjects in the presence of rhGM-CSF and rhIL-4 for
6 days, were incubated with 1 × 105
allogeneic naïve
CD4+
T cells at 1:40, 1:20, and 1:10 ratios for 5 days
followed by a 6-hour pulse of 3
H-TdR. Results are
expressed as mean ± SE cpm of triplicate co-
cultures. Statistical significance was determined
using one-way ANOVA.
RESULTS
35. Translational Oncology 2015 8, 327-338DOI: (10.1016/j.tranon.2015.06.005)
.
Effects of standard-dose rhIL-4 and/or rhIL-12 and low-
dose SKA-IL-4 and/or SKA-IL-12 on APC activity in MLR of
MoDCs from nonmetastatic colon carcinoma patients (n =
6) and from metastatic colon carcinoma patients (n = 7).
MoDCs were untreated or pretreated with SKA-IL-4 (48
hours) and SKA-IL-12 (24 hours) as single agents or
sequentially in parallel to the rh cytokines, and subjected
to MLR with allogeneic naïve T cells in different MoDC-to-
T cell ratios. The figure shows the mean percentages ± SE
of 3H-TdR incorporation in cpm. Statistical significance was
determined using one-way ANOVA.
Rh/SKA cytokine pretreated nonmetastatic/metastatic
colon carcinoma MoDCs versus untreated
nonmetastatic/metastatic colon carcinoma MoDCs: *P <
.05 and **P < .01.
Nonmetastatic colon carcinoma MoDCs versus metastatic
colon carcinoma MoDCs: ●●
P < .01 and ●●●
P < .0001.
RESULTS*
RECOMBINANT HIGH DOSE
LOW DOSE SKA
36. IL-4 (10 fg/ml SKA) IL-12 (10 fg/ml SKA)
IFN-g (10 fg/ml SKA)
IL-12 (10 fg/ml SKA)
GUNA IMMUNITY SYSTEM ACTIVATION IN CANCER