PD-1 Didn’t Work…

NEW YORK, NY, May 3, 2012 – The Ludwig Institute for Cancer Research (LICR) announced today the launch of a private biotechnology enterprise, iTeos Therapeutics SA, to develop a novel pre-clinical pipeline of immunomodulators to stimulate the immune system’s ability to attack cancer

iTeos co-founder and CEO Michel Detheux, Ph.D. “We now know that combination treatments are likely to be more effective than single therapies in controlling and eventually eliminating cancer. iTeos will pursue this approach by combining existing vaccines with new immunodulatory compounds based on research that has just emerged from the Ludwig Institute.”

Cancer immunotherapy

— leveraging the body’s own immune system to attack and destroy tumors — is emerging as a promising method for cancer treatment. Clinical testing of several immunotherapeutic approaches has shown variable success. Tumors often develop survival mechanisms to prevent the attack from the immune system. Researchers are now looking to evaluate the mechanisms that enable these tumors to escape detection by the immune system.

Previously, Brussels scientists from LICR and the de Duve Institute at the Université catholique de Louvain (UCL) studied one enzyme that proved to do just that. It is known as indoleamine 2,3 dioxygenase or IDO1 for short. IDO1 is expressed in many cancers, including prostate, colon, pancreas and cervical tumors. IDO1 blocks the immune system’s ability to reject those tumors, by depriving immune cells of tryptophan. Tryptophan is one of the essential amino acids for the body.

Tryptophan is an amino acid needed for normal growth in infants and for nitrogen balance in adults. It is an essential amino acid, which means your body cannot produce it — you must get it from your diet.

Tryptophan can be found in:

• Cheese
•Chicken
• Eggs
• Fish
• Milk
• Nuts
• Peanut butter
• Peanuts
• Pumpkin seeds
• Sesame seeds
• Soy
• Tofu
• Turkey
Scientists from the Ludwig Institute for Cancer Research (LICR) in Brussels identified a new target for cancer therapy, an enzyme which prevents the immune system from recognizing and destroying certain types of tumors. Called tryptophan 2,3-dioxygenase or TDO, the enzyme works by depriving immune cells of tryptophan, an amino acid essential to their activity. TDO is produced by a significant number of human tumors including melanomas.

The Ludwig Institute is now applying this knowledge and now is investigating inhibitors of these two enzymes (IDO and TDO).

“Little is known about the TDO enzyme and its ability to trick the immune system and prevent it from destroying deadly tumors” said study lead investigator, Benoit J. Van den Eynde, M.D., Ph.D., Brussels Branch Director at LICR.

The (Belgium) team of scientists then developed an active compound to inhibit TDO enzymatic activity. “Our study showed quite beautifully that the TDO inhibitor restored the ability of mice to reject tumors despite the presence of TDO in tumor cells,” said Dr. Van den Eynde

Cancer research is like analyzing an onion; you pull one layer off at a time and discover another layer of suppression from the tumor’s microenvironment. We are forever gaining knowledge about the immune system. The CURE will come from Combinatorial Therapy!!!

NEW YORK, NY, May 3, 2012 – The Ludwig Institute for Cancer Research (LICR) announced today the launch of a private biotechnology enterprise, iTeos Therapeutics SA, to develop a novel pre-clinical pipeline of immunomodulators to stimulate the immune system’s ability to attack cancer

iTeos co-founder and CEO Michel Detheux, Ph.D. “We now know that combination treatments are likely to be more effective than single therapies in controlling and eventually eliminating cancer. iTeos will pursue this approach by combining existing vaccines with new immunodulatory compounds based on research that has just emerged from the Ludwig Institute.”

Cancer immunotherapy

— leveraging the body’s own immune system to attack and destroy tumors — is emerging as a promising method for cancer treatment. Clinical testing of several immunotherapeutic approaches has shown variable success. Tumors often develop survival mechanisms to prevent the attack from the immune system. Researchers are now looking to evaluate the mechanisms that enable these tumors to escape detection by the immune system.

Previously, Brussels scientists from LICR and the de Duve Institute at the Université catholique de Louvain (UCL) studied one enzyme that proved to do just that. It is known as indoleamine 2,3 dioxygenase or IDO1 for short. IDO1 is expressed in many cancers, including prostate, colon, pancreas and cervical tumors. IDO1 blocks the immune system’s ability to reject those tumors, by depriving immune cells of tryptophan. Tryptophan is one of the essential amino acids for the body.

Tryptophan is an amino acid needed for normal growth in infants and for nitrogen balance in adults. It is an essential amino acid, which means your body cannot produce it — you must get it from your diet.

Tryptophan can be found in:

• Cheese
•Chicken
• Eggs
• Fish
• Milk
• Nuts
• Peanut butter
• Peanuts
• Pumpkin seeds
• Sesame seeds
• Soy
• Tofu
• Turkey
Scientists from the Ludwig Institute for Cancer Research (LICR) in Brussels identified a new target for cancer therapy, an enzyme which prevents the immune system from recognizing and destroying certain types of tumors. Called tryptophan 2,3-dioxygenase or TDO, the enzyme works by depriving immune cells of tryptophan, an amino acid essential to their activity. TDO is produced by a significant number of human tumors including melanomas.

The Ludwig Institute is now applying this knowledge and now is investigating inhibitors of these two enzymes (IDO and TDO).

“Little is known about the TDO enzyme and its ability to trick the immune system and prevent it from destroying deadly tumors” said study lead investigator, Benoit J. Van den Eynde, M.D., Ph.D., Brussels Branch Director at LICR.

The (Belgium) team of scientists then developed an active compound to inhibit TDO enzymatic activity. “Our study showed quite beautifully that the TDO inhibitor restored the ability of mice to reject tumors despite the presence of TDO in tumor cells,” said Dr. Van den Eynde

Cancer research is like analyzing an onion; you pull one layer off at a time and discover another layer of suppression from the tumor’s microenvironment. We are forever gaining knowledge about the immune system. The CURE will come from Combinatorial Therapy!!!

NEW YORK, NY, May 3, 2012 – The Ludwig Institute for Cancer Research (LICR) announced today the launch of a private biotechnology enterprise, iTeos Therapeutics SA, to develop a novel pre-clinical pipeline of immunomodulators to stimulate the immune system’s ability to attack cancer

iTeos co-founder and CEO Michel Detheux, Ph.D. “We now know that combination treatments are likely to be more effective than single therapies in controlling and eventually eliminating cancer. iTeos will pursue this approach by combining existing vaccines with new immunodulatory compounds based on research that has just emerged from the Ludwig Institute.”

Cancer immunotherapy

— leveraging the body’s own immune system to attack and destroy tumors — is emerging as a promising method for cancer treatment. Clinical testing of several immunotherapeutic approaches has shown variable success. Tumors often develop survival mechanisms to prevent the attack from the immune system. Researchers are now looking to evaluate the mechanisms that enable these tumors to escape detection by the immune system.

Previously, Brussels scientists from LICR and the de Duve Institute at the Université catholique de Louvain (UCL) studied one enzyme that proved to do just that. It is known as indoleamine 2,3 dioxygenase or IDO1 for short. IDO1 is expressed in many cancers, including prostate, colon, pancreas and cervical tumors. IDO1 blocks the immune system’s ability to reject those tumors, by depriving immune cells of tryptophan. Tryptophan is one of the essential amino acids for the body.

Tryptophan is an amino acid needed for normal growth in infants and for nitrogen balance in adults. It is an essential amino acid, which means your body cannot produce it — you must get it from your diet.

Tryptophan can be found in:

• Cheese
•Chicken
• Eggs
• Fish
• Milk
• Nuts
• Peanut butter
• Peanuts
• Pumpkin seeds
• Sesame seeds
• Soy
• Tofu
• Turkey
Scientists from the Ludwig Institute for Cancer Research (LICR) in Brussels identified a new target for cancer therapy, an enzyme which prevents the immune system from recognizing and destroying certain types of tumors. Called tryptophan 2,3-dioxygenase or TDO, the enzyme works by depriving immune cells of tryptophan, an amino acid essential to their activity. TDO is produced by a significant number of human tumors including melanomas.

The Ludwig Institute is now applying this knowledge and now is investigating inhibitors of these two enzymes (IDO and TDO).

“Little is known about the TDO enzyme and its ability to trick the immune system and prevent it from destroying deadly tumors” said study lead investigator, Benoit J. Van den Eynde, M.D., Ph.D., Brussels Branch Director at LICR.

The (Belgium) team of scientists then developed an active compound to inhibit TDO enzymatic activity. “Our study showed quite beautifully that the TDO inhibitor restored the ability of mice to reject tumors despite the presence of TDO in tumor cells,” said Dr. Van den Eynde

Cancer research is like analyzing an onion; you pull one layer off at a time and discover another layer of suppression from the tumor’s microenvironment. We are forever gaining knowledge about the immune system. The CURE will come from Combinatorial Therapy!!!

Actually, the PD-1 did work for your father. If he was on anti-PD1 for a year and his tumors shrunk, that is a great success in the world of melanoma! Unfortunately, we don't have anything yet that can cure melanoma. Yes, some small percentage of patients get long-term responses to a treatment (like your father did); a few even remain NED for the rest of their lives. But by-and-large a "successful" melanoma treatment reduces the tumor load for a while. Then the tumors start growing again. That's just the way it is.

We are lucky to be living at a time when more and more new melanoma treatments are being discovered and tested. Now we can try treatment A and get 6 good months. Then we can try treatment B and get maybe another 8 or 10 good months. And continue that way as long as we can or until we happen to be one of the lucky ones who go into remission for a long, long time. 

They are now doing clinical trials of ipi + antii-PD1– either in combination or in sequence. The results so far seem very promising. So goiong from anti-PD1 to ipi might be a very good thing for your father to try. I might just be the thing that will keep him NED for a long, long time. I sure hope so!

Actually, the PD-1 did work for your father. If he was on anti-PD1 for a year and his tumors shrunk, that is a great success in the world of melanoma! Unfortunately, we don't have anything yet that can cure melanoma. Yes, some small percentage of patients get long-term responses to a treatment (like your father did); a few even remain NED for the rest of their lives. But by-and-large a "successful" melanoma treatment reduces the tumor load for a while. Then the tumors start growing again. That's just the way it is.

We are lucky to be living at a time when more and more new melanoma treatments are being discovered and tested. Now we can try treatment A and get 6 good months. Then we can try treatment B and get maybe another 8 or 10 good months. And continue that way as long as we can or until we happen to be one of the lucky ones who go into remission for a long, long time. 

They are now doing clinical trials of ipi + antii-PD1– either in combination or in sequence. The results so far seem very promising. So goiong from anti-PD1 to ipi might be a very good thing for your father to try. I might just be the thing that will keep him NED for a long, long time. I sure hope so!

Actually, the PD-1 did work for your father. If he was on anti-PD1 for a year and his tumors shrunk, that is a great success in the world of melanoma! Unfortunately, we don't have anything yet that can cure melanoma. Yes, some small percentage of patients get long-term responses to a treatment (like your father did); a few even remain NED for the rest of their lives. But by-and-large a "successful" melanoma treatment reduces the tumor load for a while. Then the tumors start growing again. That's just the way it is.

We are lucky to be living at a time when more and more new melanoma treatments are being discovered and tested. Now we can try treatment A and get 6 good months. Then we can try treatment B and get maybe another 8 or 10 good months. And continue that way as long as we can or until we happen to be one of the lucky ones who go into remission for a long, long time. 

They are now doing clinical trials of ipi + antii-PD1– either in combination or in sequence. The results so far seem very promising. So goiong from anti-PD1 to ipi might be a very good thing for your father to try. I might just be the thing that will keep him NED for a long, long time. I sure hope so!

I am happy to hear that your father had a good, although not complete, response to the PD-1.  This is good news, please don't minimize this.  

My only suggestion is if you are considering going to NIH – you should do it soon.  The workup and process takes time and I'd get the ball rolling asap.  It doesn't hurt to go have a screening visit to get their opion and see what they have to offer.  

All the best of luck to you and your father.

Troy

I am happy to hear that your father had a good, although not complete, response to the PD-1.  This is good news, please don't minimize this.  

My only suggestion is if you are considering going to NIH – you should do it soon.  The workup and process takes time and I'd get the ball rolling asap.  It doesn't hurt to go have a screening visit to get their opion and see what they have to offer.  

All the best of luck to you and your father.

Troy

I am happy to hear that your father had a good, although not complete, response to the PD-1.  This is good news, please don't minimize this.  

My only suggestion is if you are considering going to NIH – you should do it soon.  The workup and process takes time and I'd get the ball rolling asap.  It doesn't hurt to go have a screening visit to get their opion and see what they have to offer.  

All the best of luck to you and your father.

Troy

Oh! I just noticed another new thread posted today. "Nivolumab/Ipilimumab Combo in Advanced Melanoma – NEJM". It provides a link to a new article in the New England Journal of Medicine talking about combining ipi + anti-PD1. Check it out!

Oh! I just noticed another new thread posted today. "Nivolumab/Ipilimumab Combo in Advanced Melanoma – NEJM". It provides a link to a new article in the New England Journal of Medicine talking about combining ipi + anti-PD1. Check it out!

Oh! I just noticed another new thread posted today. "Nivolumab/Ipilimumab Combo in Advanced Melanoma – NEJM". It provides a link to a new article in the New England Journal of Medicine talking about combining ipi + anti-PD1. Check it out!

Jim,

That is some great stuff.  I've been reading the book, "Enzymes, The fountain of Life".  It's a fascinating read.  Europe is much further along in this area than the US.  I would love to see more study in the US in this area.

Brian

Jim,

That is some great stuff.  I've been reading the book, "Enzymes, The fountain of Life".  It's a fascinating read.  Europe is much further along in this area than the US.  I would love to see more study in the US in this area.

Brian

Jim,

That is some great stuff.  I've been reading the book, "Enzymes, The fountain of Life".  It's a fascinating read.  Europe is much further along in this area than the US.  I would love to see more study in the US in this area.

Brian