Better explicating the strengths and shortcomings of these models will help refine projections and improve transparency in the years ahead.
Image credit: Witsawat.S.
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Communicated by Lewis T. Williams, Chiron Technologies, Emeryville, CA, and University of California, San Francisco, CA (received for review July 27, 1998)
Article Figures & SI
Figures
- Figure 1
Systemic administration of IL-2 can enhance the efficacy of tumor-lysate pulsed DC to induce specific protective immunity to lethal tumor challenge. As described, mice were immunized twice s.c. in the right flank with MCA-207 tumor lysate-pulsed DC and received i.p. injections of IL-2 after each immunization. Control groups of mice received either HBSS, tumor lysate alone, unpulsed DC alone, MCA-207 tumor lysate-pulsed DC alone, or IL-2 alone. All mice were then rechallenged with a lethal dose of either MCA-207 (Upper) or the unrelated MCA-102 (Lower) viable tumor cells by s.c. injection in the left flank. Data are reported as the average tumor area ± SEM of five or more mice/group.
- Figure 2
Systemic administration of IL-2 can enhance the capacity of MCA-207 tumor lysate-pulsed DC to induce tumor-specific CTL (Top and Middle) and IFN-γ production (Bottom) in vivo. Mice were immunized twice weekly following the schedule described in Fig. 1. Spleens were harvested 7 days after the final IL-2 (or HBSS) injection from mice treated with either HBSS, MCA-207 tumor lysate-pulsed DC plus IL-2, MCA-207 tumor lysate-pulsed DC alone, or IL-2 alone. Details of the generation and testing of these CTL are provided in Materials and Methods. Values are the mean ± SEM of triplicate wells at a 100:1 effector-to-target ratio. For measurement of IFN-γ production (Bottom), splenic T cells from the treated mice were stimulated in vitro as described. Culture supernatants were harvested 48 hr later and evaluated for IFN-γ levels by ELISA (in units/ml; mean ± SEM of triplicate samples).
- Figure 3
Treatment with the combination of tumor lysate-pulsed DC and IL-2 can prolong survival and result in cures of mice bearing established pulmonary metastases. Mice harboring MCA-207 lung metastases were immunized three times on days 3, 7, and 11 (Upper) or days 7, 10, and 13 (Lower) after tumor injection. IL-2 was given i.p. twice daily at 20,000 IU/dose (Upper) or 40,000 IU/dose (Lower) for 3 consecutive days after each immunization. Control groups of mice received HBSS, tumor lysate plus IL-2, unpulsed DC plus IL-2, or IL-2 alone. Survival was monitored over time after tumor injection, and the MST (in days) was determined.
- Figure 4
Treatment of mice with tumor lysate-pulsed DC and the systemic administration of IL-2 results in regression of established, 14-day s.c. tumor. A total of 2 × 105 syngeneic MCA-207 sarcoma cells were injected s.c. in the right flank. Mice bearing 14-day tumors were then treated weekly three times with 1 × 106 MCA-207 tumor lysate-pulsed DC in the left flank. IL-2 was given i.p. twice daily at 20,000 IU/dose for 5 consecutive days after each immunization. Control groups of mice received HBSS, MCA-207 tumor lysate-pulsed DC alone, or IL-2 alone. The size of the tumors was assessed in a blinded, coded fashion twice weekly and recorded as tumor area (in mm2).
- Figure 5
Combination therapy with tumor lysate-pulsed DC plus IL-2 can prolong survival and result in cures of mice bearing established, 14-day s.c. tumor. Mice were treated 14 days after tumor injection as described in Fig. 4. Survival was monitored over time after tumor injection, and the MST (in days) was determined.
- Figure 6
Treatment of mice with tumor lysate-pulsed DC and the systemic administration of IL-2 results in partial regression of established, 28-day s.c. tumor. Mice were treated 28 days after tumor injection as described in Fig. 4. The size of the tumors was assessed in a coded, blinded fashion and recorded as tumor area (in mm2) by measuring the largest perpendicular diameters. Data are reported as the average tumor area ± SEM of five or more mice/group.
Tables
- Table 1
Systemic administration of IL-2 can enhance the therapeutic efficacy of tumor lysate-pulsed DC against established pulmonary metastases
Pulmonary metastases Treatment* No. of metastases (range)† Mean 3 day HBSS ≥250 250 IL-2 143–167 155‡ Lysate 243–250 249 Unpulsed DC 217–250 249 TP-DC 16–42 28‡ TP-DC + IL-2 0–4 1‡ 7 day HBSS ≥250 250 IL-2 141–186 159‡ Lysate ≥250 250 Lysate + IL-2 143–192 163‡ Unpulsed DC ≥250 250 TP-DC 138–184 155‡ TP-DC + IL-2 4–21 10‡ -
↵* Number of MCA-207 tumor cells injected i.v. was 1.5 × 105 A total of 1 × 106 MCA-207 tumor lysate-pulsed DC were injected twice on days 3 and 7 or days 7 and 11 after tumor injection. IL-2 was administered i.p. twice daily at 20,000 IU/dose from days 3–9 or 40,000 IU/dose from days 7 to 13.
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↵† Mice were euthanized at day 14 (3-day model) or day 15 (7-day model).
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↵‡ Mann-Whitney U test; P < 0.01 (compared to group receiving HBSS).
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Systemic administration of interleukin 2 enhances the therapeutic efficacy of dendritic cell-based tumor vaccines
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