Presentation is loading. Please wait.

Presentation is loading. Please wait.

Volume 14, Issue 1, Pages (January 2012)

Similar presentations


Presentation on theme: "Volume 14, Issue 1, Pages (January 2012)"— Presentation transcript:

1 Volume 14, Issue 1, Pages 80-90 (January 2012)
Feasibility and safety of adoptive immunotherapy with ex vivo-generated autologous, cytotoxic T lymphocytes in patients with solid tumor  Daniela Montagna, Ilaria Turin, Roberta Schiavo, Enrica Montini, Nadia Zaffaroni, Raffaella Villa, Simona Secondino, Ilaria Schiavetto, Laura Caliogna, Franco Locatelli, Virginia Libri, Andrea Pession, Roberto Tonelli, Rita Maccario, Salvatore Siena, Paolo Pedrazzoli  Cytotherapy  Volume 14, Issue 1, Pages (January 2012) DOI: / Copyright © 2012 International Society for Cellular Therapy Terms and Conditions

2 Figure 1 Cytotoxic activity of anti-tumor CTL lines. Infused CTL were tested against autologous TC (diamonds) and autologous T-lymphoblastoid cell line (T-LCL) (squares) at effector:target (E:T) ratios ranging from 50:1 to 0.1:1, and representative results obtained at E:T ratios ranging from 25:1 to 3:1 are reported. Cytotherapy  , 80-90DOI: ( / ) Copyright © 2012 International Society for Cellular Therapy Terms and Conditions

3 Figure 2 Telomere length and telomerase activity analysis of anti-tumor CTL. (A) Representative experiments of TRF length distribution of anti-tumor CTL lines after tumor-specific stimulation and one or two rounds of antigen antigen-independent expansion. Patient 1, anti-tumor CTL after one round of antigen-independent expansion; patient 6, telomere length after one and two rounds of antigen-independent expansion, respectively; patient 2, telomere length after tumor-specific stimulation and one round of antigen antigen-independent expansion, respectively. GM847 and HeLa cell lines were used as controls; ND, non-digested DNA. Peak value of TRF lengths are reported in the box. (B) Telomerase activity of anti-tumor CTL cultures at the same passages of expansion as detected by the TRAP assay using two protein concentrations. The location and length of the internal amplification standard (ITAS, 36 bp) and of the first telomerase product (50 bp) are reported. R8 is an external quantitative standard. The blank represents a negative control to which no protein extract was added. The positivity (+) for telomerase activity is reported in the box. Cytotherapy  , 80-90DOI: ( / ) Copyright © 2012 International Society for Cellular Therapy Terms and Conditions

4 Figure 3 Immunologic follow-up of patients. Patients received a variable number of infusions with escalating doses of CTL. Low-dose IL-2 (1m U/day) was administered subcutaneously for 2 weeks following each CTL infusion. Evaluation of anti-tumor immunity was performed 7–10 days after each CTL infusion. Results were derived from the mean of duplicate wells. Data reported in the figure were calculated after subtracting assay background (average of spots present in 24 wells containing complete medium alone) and non-stimulated cell background (average of spots present in 10 wells containing responder cells alone). The x-axis shows the days after the beginning of treatment; the y-axis shows the number of IFN-γ-secreting cells represented as the number of spots/105 cells (mean spots of duplicate experiments). (A) IFN-γ production in patient 1 during the first 150 days from the beginning of treatment. (B) IFN-γ production in patient 5 at two different time intervals: during the first 2 months and from 180 to 250 days of treatment. (C) IFN-γ production in patient 5 from 900 to 1500 days of treatment. §Number of CTL infused × 107. Down arrow, time of CTL infusions. ¶Patients received lymphodepleting chemotherapy on days 1 to 4 (see the Methods). Cytotherapy  , 80-90DOI: ( / ) Copyright © 2012 International Society for Cellular Therapy Terms and Conditions

5 Figure 4 Clonal expansion of anti-tumor CTL lines. Four representative patterns of TCR–Vβ gene subfamilies (among 24 studied) of two different batches of anti-tumor CTL lines, derived from patients 5 (02D CTL#5 and 02F CTL#5) and 6 (06A CTL#6 and 06B CTL#6) and from PBMC of these patients 14, 35 and 63 days after one representative CTL infusion, are shown. In particular, for patient 5 (B) the results refer to the pattern of infused CTL and PBMC starting from CTL infusion at day (day + 14 and day + 63), while in the case of patient 6 (A) the results refer to CTL infusion at day Cytotherapy  , 80-90DOI: ( / ) Copyright © 2012 International Society for Cellular Therapy Terms and Conditions


Download ppt "Volume 14, Issue 1, Pages (January 2012)"

Similar presentations


Ads by Google