$PVCT Melanoma shows improved regression with c
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Posted On: 11/18/2014 2:07:23 PM
$PVCT
Melanoma shows improved regression with combination of PV-10 and checkpoint inhibitor
Last updated: Today at 3am PST
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Melanoma / Skin Cancer
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Intralesional PV-10 used in combination with immune check point inhibitors improved regression of melanoma in a mouse model and increased markers of T cell activity in comparison to either treatment alone.
Melanoma
The new research presented at SITC's Annual Meeting suggests melanoma regression improves when PV-10 is used alongside immune check point inhibitors.
The abstract - presented at the Society for Immunotherapy of Cancer (SITC) 29th Annual Meeting, November 6-9, in National Harbor, MD - furthermore showed combination therapy of intralesional (IL) PV-10 and anti-PD-L1 antibodies enhanced regression of "bystander" (uninjected lesions) in comparison to either treatment used alone.
In an earlier phase 2 clinical trial, IL injection with PV-10 into the lesions of 80 stage 3 and 4 melanoma patients, with disease refractory to a median of six prior interventions, produced a best overall response rate of 51% and a complete response rate of 26% in target lesions.
Notably, responses in the study were dependent on untreated disease burden, with complete response achieved in 50% of patients receiving PV-10 injections to all their disease.
PV-10 - a 10% solution of Rose Bengal originally used as an agent to stain necrotic tissue in the cornea - has been developed to selectively target and destroy cancer cells without harming surrounding healthy tissue, minimizing potential for side effects.
The first checkpoint inhibitor ipilimumab was approved in March 2011 for treatment of advanced melanoma. Checkpoint inhibitors are a class of drugs designed to release the "molecular brakes" that cancer cells apply to the body's immune system.
"The spirit of our study was to determine whether combining PV-10 with a checkpoint inhibitor would enhance the systematic immune responses of the initial injection of PV-10," explains Shari Pilon-Thomas, the first author from Moffitt Cancer Center in Tampa, FL.
In addition to anti-CTLA-4, for the first time, the team included the second-generation immune check point inhibitors anti-PD-1 and anti-PD-L1.
T cells injected with PV-10, anti-PD-L1 produced more interferon gamma
For the main study, mice had melanoma cell lines implanted into one flank and then, 7-14 days later, underwent IL injections into these tumors with PV-10. Three days later, they received intraperitoneal injections of anti-CTLA-4, anti-PD-1 or anti-PD-L1 antibodies, repeated every 3 days until the end of the experiments.
Additionally, phosphate buffered saline (PBS) was used as a control for PV-10 and NrlgG (a non-reactive antibody) as a control for the checkpoint inhibitors. Each of the four study arms contained five to 10 mice.
Following treatment, mice had the area of the original tumor measured at different time points and levels of interferon gamma (indicating T cell reactivity) measured at days 7-14 after IL PV-10 injection. Additionally, for mice treated with anti-PD-L1, a bilateral model was investigated where mice had melanoma cell lines injected into both flanks, but only the right flank underwent IL PV-10 injections.
For "single" tumor models, results show mice injected with PV-10 and anti-PD-L1 had a significant delay in tumor growth compared with mice injected with PBS + NrlgG, PBS + anti-PD-L1, or PV-10 + NrlgG (p<0.05 for all).
Furthermore, T cells isolated from the spleens of mice injected with both PV-10 and anti-PD-L1 produced significantly more interferon gamma in comparison with the other three groups (p<0.05).
For mice injected with PV-10 and anti-PD-1 antibodies, there was a significant decrease in tumor growth, compared with mice receiving anti-PD-1 alone (p<0.05); while for the anti-CTLA-4 group, not enough mice were treated to demonstrate statistically significant differences.
Combination therapy with IL injection of PV-10 and immune check point inhibitors
In the "bilateral" model, mice who received combination treatment with PV-10 and anti-PD-L1 also showed significant delays in tumor growth in untreated "bystander lesions," compared with mice injected with PBS + NrlgG, PBS + anti-PD-L1, or PV10 + NrlgG (p<0.01 for all).
"This feasibility study supports combination therapy with IL injection of PV-10 and immune check point inhibitors to improve systematic immune responses," says Pilon-Thomas.
The mechanism, she adds, is thought to be that injection of PV-10 into melanoma lesions results in tumor cells releasing antigens that induce T cell immunity, with the checkpoint inhibitors then "releasing the brakes" on the resulting T cells. Next, the team plans to investigate the types of immune cells released at the tumor site.
"These findings support commencement of clinical testing of PV-10 in combination anti-CLTA-4, anti-PD-1 or anti-PD-L1 agents," says Eric Wachter, chief technology officer at Provectus, adding the company hopes to start phase 1 studies of the combination in early 2015.
"While there's a lot of work ahead of us, the promise looks great," he says.
Written by Janet Fricker
Melanoma shows improved regression with combination of PV-10 and checkpoint inhibitor
Last updated: Today at 3am PST
47 Like12
Melanoma / Skin Cancer
Clinical Trials / Drug Trials
add your opinion
MNT featured
Ratings for this article (click to rate)
Public / Patient:
1 2 3 4 5
Health Professionals:
1 2 3 4 5
Intralesional PV-10 used in combination with immune check point inhibitors improved regression of melanoma in a mouse model and increased markers of T cell activity in comparison to either treatment alone.
Melanoma
The new research presented at SITC's Annual Meeting suggests melanoma regression improves when PV-10 is used alongside immune check point inhibitors.
The abstract - presented at the Society for Immunotherapy of Cancer (SITC) 29th Annual Meeting, November 6-9, in National Harbor, MD - furthermore showed combination therapy of intralesional (IL) PV-10 and anti-PD-L1 antibodies enhanced regression of "bystander" (uninjected lesions) in comparison to either treatment used alone.
In an earlier phase 2 clinical trial, IL injection with PV-10 into the lesions of 80 stage 3 and 4 melanoma patients, with disease refractory to a median of six prior interventions, produced a best overall response rate of 51% and a complete response rate of 26% in target lesions.
Notably, responses in the study were dependent on untreated disease burden, with complete response achieved in 50% of patients receiving PV-10 injections to all their disease.
PV-10 - a 10% solution of Rose Bengal originally used as an agent to stain necrotic tissue in the cornea - has been developed to selectively target and destroy cancer cells without harming surrounding healthy tissue, minimizing potential for side effects.
The first checkpoint inhibitor ipilimumab was approved in March 2011 for treatment of advanced melanoma. Checkpoint inhibitors are a class of drugs designed to release the "molecular brakes" that cancer cells apply to the body's immune system.
"The spirit of our study was to determine whether combining PV-10 with a checkpoint inhibitor would enhance the systematic immune responses of the initial injection of PV-10," explains Shari Pilon-Thomas, the first author from Moffitt Cancer Center in Tampa, FL.
In addition to anti-CTLA-4, for the first time, the team included the second-generation immune check point inhibitors anti-PD-1 and anti-PD-L1.
T cells injected with PV-10, anti-PD-L1 produced more interferon gamma
For the main study, mice had melanoma cell lines implanted into one flank and then, 7-14 days later, underwent IL injections into these tumors with PV-10. Three days later, they received intraperitoneal injections of anti-CTLA-4, anti-PD-1 or anti-PD-L1 antibodies, repeated every 3 days until the end of the experiments.
Additionally, phosphate buffered saline (PBS) was used as a control for PV-10 and NrlgG (a non-reactive antibody) as a control for the checkpoint inhibitors. Each of the four study arms contained five to 10 mice.
Following treatment, mice had the area of the original tumor measured at different time points and levels of interferon gamma (indicating T cell reactivity) measured at days 7-14 after IL PV-10 injection. Additionally, for mice treated with anti-PD-L1, a bilateral model was investigated where mice had melanoma cell lines injected into both flanks, but only the right flank underwent IL PV-10 injections.
For "single" tumor models, results show mice injected with PV-10 and anti-PD-L1 had a significant delay in tumor growth compared with mice injected with PBS + NrlgG, PBS + anti-PD-L1, or PV-10 + NrlgG (p<0.05 for all).
Furthermore, T cells isolated from the spleens of mice injected with both PV-10 and anti-PD-L1 produced significantly more interferon gamma in comparison with the other three groups (p<0.05).
For mice injected with PV-10 and anti-PD-1 antibodies, there was a significant decrease in tumor growth, compared with mice receiving anti-PD-1 alone (p<0.05); while for the anti-CTLA-4 group, not enough mice were treated to demonstrate statistically significant differences.
Combination therapy with IL injection of PV-10 and immune check point inhibitors
In the "bilateral" model, mice who received combination treatment with PV-10 and anti-PD-L1 also showed significant delays in tumor growth in untreated "bystander lesions," compared with mice injected with PBS + NrlgG, PBS + anti-PD-L1, or PV10 + NrlgG (p<0.01 for all).
"This feasibility study supports combination therapy with IL injection of PV-10 and immune check point inhibitors to improve systematic immune responses," says Pilon-Thomas.
The mechanism, she adds, is thought to be that injection of PV-10 into melanoma lesions results in tumor cells releasing antigens that induce T cell immunity, with the checkpoint inhibitors then "releasing the brakes" on the resulting T cells. Next, the team plans to investigate the types of immune cells released at the tumor site.
"These findings support commencement of clinical testing of PV-10 in combination anti-CLTA-4, anti-PD-1 or anti-PD-L1 agents," says Eric Wachter, chief technology officer at Provectus, adding the company hopes to start phase 1 studies of the combination in early 2015.
"While there's a lot of work ahead of us, the promise looks great," he says.
Written by Janet Fricker
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I'm in it to win it!
NASDAQ DIP and RIP
Here is the best word that describes what i do here.
Intuitive;
means having the ability to understand or know something without any direct evidence or reasoning process.
I was born with it, I'm truly blessed!
Alway's searching for winners'
NASDAQ DIP and RIP
Here is the best word that describes what i do here.
Intuitive;
means having the ability to understand or know something without any direct evidence or reasoning process.
I was born with it, I'm truly blessed!
Alway's searching for winners'
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