Limits...
In vivo synergy of radiation and hu14.18-IL2 immunocytokine results in a memory T cell response in a syngeneic murine melanoma model

View Article: PubMed Central - HTML

AUTOMATICALLY GENERATED EXCERPT
Please rate it.

C57BL/6 mice were engrafted with syngeneic GD2-expressing B78 melanoma... Mice then received 5 daily intra-tumor injections of human IgG, hu14.18 mAb, or hu14.18-IL2 IC... NK or T cell depletion was achieved by intraperitoneal injection of a depleting mAb (NK1.1 or CD4/CD8 mAbs)... After 90 days mice rendered disease-free by initial treatment were re-challenged with a second injection of B78 melanoma... After an additional 30 days mice not developing tumors were injected at distinct sites with syngeneic B16 melanoma (related to B78 but lacking GD2) and Panc02 pancreatic cancer cells... In tumor-bearing mice we observe synergy between RT and anti-GD2 mAb resulting in tumor regression and improved animal survival (Figure 1)... This interaction of RT and hu14.18 is inhibited by depletion of NK cells and is not observed in mice that lack Fcϒ receptors... Synergy is markedly enhanced by substituting mAb with hu14.18-IL2 (Figure 2), resulting in durable complete resolution of tumors in 71% (22/31) of animals... Among mice rendered disease-free by initial treatment and remaining disease-free after B78 re-challenge, 75% (9/12) rejected subsequent engraftment with related GD2-deficient B16 melanoma cells... None of these rejected simultaneous injection of Panc02 cells and no age-matched controls (0/11) rejected the same B16 cells... We present evidence of synergy between RT and hu14.18-IL2 resulting in a memory T cell response... Our findings suggest a therapeutic opportunity for combining RT with immunotherapies that simultaneously target innate immune response and T-cell activation.

No MeSH data available.


Related in: MedlinePlus

Enhanced in vivo synergy elicited by radiation and hu14.18-IL2 immunocytokine in a murine melanoma tumor model.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
getmorefigures.php?uid=PMC4288538&req=5

Figure 2: Enhanced in vivo synergy elicited by radiation and hu14.18-IL2 immunocytokine in a murine melanoma tumor model.

Mentions: In tumor-bearing mice we observe synergy between RT and anti-GD2 mAb resulting in tumor regression and improved animal survival (Figure 1). This interaction of RT and hu14.18 is inhibited by depletion of NK cells and is not observed in mice that lack Fcϒ receptors. Synergy is markedly enhanced by substituting mAb with hu14.18-IL2 (Figure 2), resulting in durable complete resolution of tumors in 71% (22/31) of animals. This synergy of RT and IC is minimally affected by NK cell depletion but is largely abrogated in nude mice and Fcϒ receptor-deficient mice. Immunohistochemistry on post-treatment tumor specimens demonstrates enhanced recruitment of CD8+ T cells to tumors following combined treatment with RT and IC. Of animals rendered disease-free following combined treatment, 90% (18/20) did not grow a tumor following a second injection with B78 cells while no age-matched control mice (0/23) rejected these cells. A subset of mice rendered disease-free following initial treatment was later depleted of T cells and none (0/5) rejected repeat engraftment with B78 cells. Among mice rendered disease-free by initial treatment and remaining disease-free after B78 re-challenge, 75% (9/12) rejected subsequent engraftment with related GD2-deficient B16 melanoma cells. None of these rejected simultaneous injection of Panc02 cells and no age-matched controls (0/11) rejected the same B16 cells.


In vivo synergy of radiation and hu14.18-IL2 immunocytokine results in a memory T cell response in a syngeneic murine melanoma model
Enhanced in vivo synergy elicited by radiation and hu14.18-IL2 immunocytokine in a murine melanoma tumor model.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4288538&req=5

Figure 2: Enhanced in vivo synergy elicited by radiation and hu14.18-IL2 immunocytokine in a murine melanoma tumor model.
Mentions: In tumor-bearing mice we observe synergy between RT and anti-GD2 mAb resulting in tumor regression and improved animal survival (Figure 1). This interaction of RT and hu14.18 is inhibited by depletion of NK cells and is not observed in mice that lack Fcϒ receptors. Synergy is markedly enhanced by substituting mAb with hu14.18-IL2 (Figure 2), resulting in durable complete resolution of tumors in 71% (22/31) of animals. This synergy of RT and IC is minimally affected by NK cell depletion but is largely abrogated in nude mice and Fcϒ receptor-deficient mice. Immunohistochemistry on post-treatment tumor specimens demonstrates enhanced recruitment of CD8+ T cells to tumors following combined treatment with RT and IC. Of animals rendered disease-free following combined treatment, 90% (18/20) did not grow a tumor following a second injection with B78 cells while no age-matched control mice (0/23) rejected these cells. A subset of mice rendered disease-free following initial treatment was later depleted of T cells and none (0/5) rejected repeat engraftment with B78 cells. Among mice rendered disease-free by initial treatment and remaining disease-free after B78 re-challenge, 75% (9/12) rejected subsequent engraftment with related GD2-deficient B16 melanoma cells. None of these rejected simultaneous injection of Panc02 cells and no age-matched controls (0/11) rejected the same B16 cells.

View Article: PubMed Central - HTML

AUTOMATICALLY GENERATED EXCERPT
Please rate it.

C57BL/6 mice were engrafted with syngeneic GD2-expressing B78 melanoma... Mice then received 5 daily intra-tumor injections of human IgG, hu14.18 mAb, or hu14.18-IL2 IC... NK or T cell depletion was achieved by intraperitoneal injection of a depleting mAb (NK1.1 or CD4/CD8 mAbs)... After 90 days mice rendered disease-free by initial treatment were re-challenged with a second injection of B78 melanoma... After an additional 30 days mice not developing tumors were injected at distinct sites with syngeneic B16 melanoma (related to B78 but lacking GD2) and Panc02 pancreatic cancer cells... In tumor-bearing mice we observe synergy between RT and anti-GD2 mAb resulting in tumor regression and improved animal survival (Figure 1)... This interaction of RT and hu14.18 is inhibited by depletion of NK cells and is not observed in mice that lack Fcϒ receptors... Synergy is markedly enhanced by substituting mAb with hu14.18-IL2 (Figure 2), resulting in durable complete resolution of tumors in 71% (22/31) of animals... Among mice rendered disease-free by initial treatment and remaining disease-free after B78 re-challenge, 75% (9/12) rejected subsequent engraftment with related GD2-deficient B16 melanoma cells... None of these rejected simultaneous injection of Panc02 cells and no age-matched controls (0/11) rejected the same B16 cells... We present evidence of synergy between RT and hu14.18-IL2 resulting in a memory T cell response... Our findings suggest a therapeutic opportunity for combining RT with immunotherapies that simultaneously target innate immune response and T-cell activation.

No MeSH data available.


Related in: MedlinePlus