Pd1 trial …. Not Working :( (Yet)

Bad link the clinical trial finder, try this:

http://www.emergingmed.com/networks/MRF/

I agree with Kyle.  You still have options. Sometimes anti-PD1 has a delayed response.  And, though I'm not clear on the location of your tumors there's something called Rose Bengal that can be injected into superficial tumors.  For a more conventional approach, it sounds like IL2 might be something well worth looking into.  MEK when combined with various BRAF products can be effective even for Brag neg patients.  Hang in there.  C

I agree with Kyle.  You still have options. Sometimes anti-PD1 has a delayed response.  And, though I'm not clear on the location of your tumors there's something called Rose Bengal that can be injected into superficial tumors.  For a more conventional approach, it sounds like IL2 might be something well worth looking into.  MEK when combined with various BRAF products can be effective even for Brag neg patients.  Hang in there.  C

Erin,

You may have failed Yervoy (anti-CTLA-4 and Anti-PD-1), but there are other therapies that may Help. Tumors secrete suppresive cytokines,proteins and enzymes (IL-10, TGF-b, Gal-3, Gal,1 and IDO) to help them avoid detection from our immune system. Yervoy and Anti-PD-1 only block two pathways.  It seem you are missing the "Danger Signal" to get the immune response started.  Your Tumors may be producing IL-10 and IDO. IDO is an enzyme that breaks down trytophan, an essential amino acid. Without Trytophan, your body can't upregulate IL-6 expression. Without IL-6, and in the presence of TGF-b, T-cells differeniate into T regulatory cells (Tregs). If IL-6 was present, the T-cells would Differeniate into TH17 and involk the "Danger Signal".

You may want to look into IDO inhibitor trial and or Anti-TGF-b trial.

IDO Pathway Inhibitor Technology

“We believe that immune system failure is a fundamental reason for the inability of the human body to successfully fight cancer cells. Research indicates that tumors can induce the human immune system to tolerate the existence of the tumor. This immune tolerance and suppression is a major barrier to successful treatment of cancer and is a significant target for new therapeutics.

Indoleamine-(2,3)-dioxygenase (IDO) pathway inhibitors, including NLG8189 (d-1-methyltryptophan, or D-1MT), represent a potential breakthrough approach to cancer therapy using small‑molecule, anti-toleragenic product candidates intended to combat the mechanisms by which tumors evade immune-mediated destruction. IDO is an enzyme that regulates immune response by suppressing effector T-cell function through depletion of the essential amino acid tryptophan. Recent studies have demonstrated that IDO is overexpressed in many cancer types, both 1) within tumor cells,where it may act as a direct defense against T-cell attack, and 2) within dendritic antigen presenting cells in the lymph nodes draining the tumor, thereby promoting peripheral tolerance to tumor-associated antigens (TAAs). When hijacked by tumors in this manner, IDO may facilitate the survival, growth, invasion, and metastasis of malignant cells expressing TAAs that might otherwise be recognized and attacked by the immune system as foreign.

The ability to eliminate the tumor-protective IDO mechanism by administering IDO pathway inhibitor drugs, such as NLG8189, may provide a therapeutic window in which to break tolerance in tumors and reverse the inhibition of immune cells. “

• Potential to break immune tolerance. Immune tolerance to tumor cells is a key barrier to the treatment of cancer. To date, few available therapies have addressed the immune escape mechanisms of cancer. We believe inhibition of the IDO pathway has the potential to block this escape and significantly enhance patient outcomes.

·        We believe IDO pathway inhibitors could also have therapeutic synergy with targeted therapeutics, radiation and immunotherapy (Yervoy). 

Best Regards,

Jimmy B

Erin,

You may have failed Yervoy (anti-CTLA-4 and Anti-PD-1), but there are other therapies that may Help. Tumors secrete suppresive cytokines,proteins and enzymes (IL-10, TGF-b, Gal-3, Gal,1 and IDO) to help them avoid detection from our immune system. Yervoy and Anti-PD-1 only block two pathways.  It seem you are missing the "Danger Signal" to get the immune response started.  Your Tumors may be producing IL-10 and IDO. IDO is an enzyme that breaks down trytophan, an essential amino acid. Without Trytophan, your body can't upregulate IL-6 expression. Without IL-6, and in the presence of TGF-b, T-cells differeniate into T regulatory cells (Tregs). If IL-6 was present, the T-cells would Differeniate into TH17 and involk the "Danger Signal".

You may want to look into IDO inhibitor trial and or Anti-TGF-b trial.

IDO Pathway Inhibitor Technology

“We believe that immune system failure is a fundamental reason for the inability of the human body to successfully fight cancer cells. Research indicates that tumors can induce the human immune system to tolerate the existence of the tumor. This immune tolerance and suppression is a major barrier to successful treatment of cancer and is a significant target for new therapeutics.

Indoleamine-(2,3)-dioxygenase (IDO) pathway inhibitors, including NLG8189 (d-1-methyltryptophan, or D-1MT), represent a potential breakthrough approach to cancer therapy using small‑molecule, anti-toleragenic product candidates intended to combat the mechanisms by which tumors evade immune-mediated destruction. IDO is an enzyme that regulates immune response by suppressing effector T-cell function through depletion of the essential amino acid tryptophan. Recent studies have demonstrated that IDO is overexpressed in many cancer types, both 1) within tumor cells,where it may act as a direct defense against T-cell attack, and 2) within dendritic antigen presenting cells in the lymph nodes draining the tumor, thereby promoting peripheral tolerance to tumor-associated antigens (TAAs). When hijacked by tumors in this manner, IDO may facilitate the survival, growth, invasion, and metastasis of malignant cells expressing TAAs that might otherwise be recognized and attacked by the immune system as foreign.

The ability to eliminate the tumor-protective IDO mechanism by administering IDO pathway inhibitor drugs, such as NLG8189, may provide a therapeutic window in which to break tolerance in tumors and reverse the inhibition of immune cells. “

• Potential to break immune tolerance. Immune tolerance to tumor cells is a key barrier to the treatment of cancer. To date, few available therapies have addressed the immune escape mechanisms of cancer. We believe inhibition of the IDO pathway has the potential to block this escape and significantly enhance patient outcomes.

·        We believe IDO pathway inhibitors could also have therapeutic synergy with targeted therapeutics, radiation and immunotherapy (Yervoy). 

Best Regards,

Jimmy B

Erin,

You may have failed Yervoy (anti-CTLA-4 and Anti-PD-1), but there are other therapies that may Help. Tumors secrete suppresive cytokines,proteins and enzymes (IL-10, TGF-b, Gal-3, Gal,1 and IDO) to help them avoid detection from our immune system. Yervoy and Anti-PD-1 only block two pathways.  It seem you are missing the "Danger Signal" to get the immune response started.  Your Tumors may be producing IL-10 and IDO. IDO is an enzyme that breaks down trytophan, an essential amino acid. Without Trytophan, your body can't upregulate IL-6 expression. Without IL-6, and in the presence of TGF-b, T-cells differeniate into T regulatory cells (Tregs). If IL-6 was present, the T-cells would Differeniate into TH17 and involk the "Danger Signal".

You may want to look into IDO inhibitor trial and or Anti-TGF-b trial.

IDO Pathway Inhibitor Technology

“We believe that immune system failure is a fundamental reason for the inability of the human body to successfully fight cancer cells. Research indicates that tumors can induce the human immune system to tolerate the existence of the tumor. This immune tolerance and suppression is a major barrier to successful treatment of cancer and is a significant target for new therapeutics.

Indoleamine-(2,3)-dioxygenase (IDO) pathway inhibitors, including NLG8189 (d-1-methyltryptophan, or D-1MT), represent a potential breakthrough approach to cancer therapy using small‑molecule, anti-toleragenic product candidates intended to combat the mechanisms by which tumors evade immune-mediated destruction. IDO is an enzyme that regulates immune response by suppressing effector T-cell function through depletion of the essential amino acid tryptophan. Recent studies have demonstrated that IDO is overexpressed in many cancer types, both 1) within tumor cells,where it may act as a direct defense against T-cell attack, and 2) within dendritic antigen presenting cells in the lymph nodes draining the tumor, thereby promoting peripheral tolerance to tumor-associated antigens (TAAs). When hijacked by tumors in this manner, IDO may facilitate the survival, growth, invasion, and metastasis of malignant cells expressing TAAs that might otherwise be recognized and attacked by the immune system as foreign.

The ability to eliminate the tumor-protective IDO mechanism by administering IDO pathway inhibitor drugs, such as NLG8189, may provide a therapeutic window in which to break tolerance in tumors and reverse the inhibition of immune cells. “

• Potential to break immune tolerance. Immune tolerance to tumor cells is a key barrier to the treatment of cancer. To date, few available therapies have addressed the immune escape mechanisms of cancer. We believe inhibition of the IDO pathway has the potential to block this escape and significantly enhance patient outcomes.

·        We believe IDO pathway inhibitors could also have therapeutic synergy with targeted therapeutics, radiation and immunotherapy (Yervoy). 

Best Regards,

Jimmy B

Can you tell me more about Rose Bengal?  My husband has huge tumors under the skin on his neck, is BRAF neg, NRAS positive and ineligible for clinical trials because of a secondary lung cancer.  He did great on carbo/taxol for awhile, failed yervoy and was put back on carbo/taxol last week with the idea that they would do two or three rounds then do radiation.  His has declined rapidly over the past week and I would welcome any ideas from anyone.  I'm calling his oncologist this morning.

Can you tell me more about Rose Bengal?  My husband has huge tumors under the skin on his neck, is BRAF neg, NRAS positive and ineligible for clinical trials because of a secondary lung cancer.  He did great on carbo/taxol for awhile, failed yervoy and was put back on carbo/taxol last week with the idea that they would do two or three rounds then do radiation.  His has declined rapidly over the past week and I would welcome any ideas from anyone.  I'm calling his oncologist this morning.

Can you tell me more about Rose Bengal?  My husband has huge tumors under the skin on his neck, is BRAF neg, NRAS positive and ineligible for clinical trials because of a secondary lung cancer.  He did great on carbo/taxol for awhile, failed yervoy and was put back on carbo/taxol last week with the idea that they would do two or three rounds then do radiation.  His has declined rapidly over the past week and I would welcome any ideas from anyone.  I'm calling his oncologist this morning.

Rose Bengal is injected into leasiona that are on the surface or close to the surface. I don't think it is FDA approved. You may want to try Imiquimod. It induces Inflamation at the site which may cause the immune system to react to the cancer.

It involks the "Danger Signal"

http://i384.photobucket.com/albums/oo290/jimmy_b/Imiquimod-induced-inflamtion.jpg

Rose Bengal is injected into leasiona that are on the surface or close to the surface. I don't think it is FDA approved. You may want to try Imiquimod. It induces Inflamation at the site which may cause the immune system to react to the cancer.

It involks the "Danger Signal"

http://i384.photobucket.com/albums/oo290/jimmy_b/Imiquimod-induced-inflamtion.jpg

Rose Bengal is injected into leasiona that are on the surface or close to the surface. I don't think it is FDA approved. You may want to try Imiquimod. It induces Inflamation at the site which may cause the immune system to react to the cancer.

It involks the "Danger Signal"

http://i384.photobucket.com/albums/oo290/jimmy_b/Imiquimod-induced-inflamtion.jpg

I agree with Kyle.  You still have options. Sometimes anti-PD1 has a delayed response.  And, though I'm not clear on the location of your tumors there's something called Rose Bengal that can be injected into superficial tumors.  For a more conventional approach, it sounds like IL2 might be something well worth looking into.  MEK when combined with various BRAF products can be effective even for Brag neg patients.  Hang in there.  C

Erin, you can click on most of the user names in green to see people's profiles, usually with treatment histories.

In my case I could hardly believe I was an IL-2 responder, for eight smaller mets (1cm or less) in my lungs. July would be 3 years since those were last detectable. Then the brain mets came and escalated (5 total over 9 months). Now I can hardly believe they've been stable or shrinking for 20 months now. June would be 2 years since last neurosurgery and radiosurgery, August would be 2 years since my 4th/last Yervoy cycle.

Since you've been through Yervoy, and are on anti-PD1, and your profile says you're in the greater Boston area, I'm assuming you're being seen by a melanoma specialist oncology practice (BIDMC, Dana Farber, Mass General, or UMASS/Worcester, etc.) 

That trial finder (run by a separate company, Emerging Med) was very impressive to me — an entire company devoted to matching patients with clinical trials. Some individual docs won't go much beyond the clinical trial offerings at their own facilities.

Erin, you can click on most of the user names in green to see people's profiles, usually with treatment histories.

In my case I could hardly believe I was an IL-2 responder, for eight smaller mets (1cm or less) in my lungs. July would be 3 years since those were last detectable. Then the brain mets came and escalated (5 total over 9 months). Now I can hardly believe they've been stable or shrinking for 20 months now. June would be 2 years since last neurosurgery and radiosurgery, August would be 2 years since my 4th/last Yervoy cycle.

Since you've been through Yervoy, and are on anti-PD1, and your profile says you're in the greater Boston area, I'm assuming you're being seen by a melanoma specialist oncology practice (BIDMC, Dana Farber, Mass General, or UMASS/Worcester, etc.) 

That trial finder (run by a separate company, Emerging Med) was very impressive to me — an entire company devoted to matching patients with clinical trials. Some individual docs won't go much beyond the clinical trial offerings at their own facilities.

Erin, you can click on most of the user names in green to see people's profiles, usually with treatment histories.

In my case I could hardly believe I was an IL-2 responder, for eight smaller mets (1cm or less) in my lungs. July would be 3 years since those were last detectable. Then the brain mets came and escalated (5 total over 9 months). Now I can hardly believe they've been stable or shrinking for 20 months now. June would be 2 years since last neurosurgery and radiosurgery, August would be 2 years since my 4th/last Yervoy cycle.

Since you've been through Yervoy, and are on anti-PD1, and your profile says you're in the greater Boston area, I'm assuming you're being seen by a melanoma specialist oncology practice (BIDMC, Dana Farber, Mass General, or UMASS/Worcester, etc.) 

That trial finder (run by a separate company, Emerging Med) was very impressive to me — an entire company devoted to matching patients with clinical trials. Some individual docs won't go much beyond the clinical trial offerings at their own facilities.

Bad link the clinical trial finder, try this:

http://www.emergingmed.com/networks/MRF/

Bad link the clinical trial finder, try this:

http://www.emergingmed.com/networks/MRF/