Good Morning…:))

The Yevoy or PD-1 therapy would take the suppressive T regulatory cells out of play, allowing any acivated T-cells to multipy. It has been shown that if IL-2 is added during the growth phase of the t-cells could jeopardize T-cell survival.

IL-2 treatment during the expansion phase was detrimental to the survival of rapidly dividing effector T cells. In contrast,

IL-2 therapy was highly beneficial during the death phase, resulting in increased proliferation and survival of Tumor-specific T cells.

IL-2 treatment also increased proliferation of resting memory T cells in the host that controlled the disease. Tumor-specific T cells in chronically infected Host also responds to IL-2 resulting in decreased tumor burden. Thus, timing of IL-2 administration and differentiation status of the T cell are critical parameters in designing IL-2 therapies (Blattman et al., 2003).

Best regards,

Jimmy b

http://2.bp.blogspot.com/-bnN8oemwz8Y/TodCXLycjRI/AAAAAAAAAg0/tJqm3oFqI10/s400/Conventional%2BEffector%2BT-Cells%2Bsecrete%2BIL-2%2B2011.jpg

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http://2.bp.blogspot.com/-bnN8oemwz8Y/TodCXLycjRI/AAAAAAAAAg0/tJqm3oFqI10/s400/Conventional%2BEffector%2BT-Cells%2Bsecrete%2BIL-2%2B2011.jpg

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Jimmy,

You are a genius; however, I am not.  I am truly grateful for every response you share; yet, I NEVER understand what you are saying.  All this death phase, effector T cells, etc. is Greek to me.  Can you please explain these things in more simplistic terms so the average (and below average…me) patients can take advantage of your advice.  Again, I am in awe of your knowledge…I just don't understand it.

Thanks a million,

Tricia 

Jimmy,

You are a genius; however, I am not.  I am truly grateful for every response you share; yet, I NEVER understand what you are saying.  All this death phase, effector T cells, etc. is Greek to me.  Can you please explain these things in more simplistic terms so the average (and below average…me) patients can take advantage of your advice.  Again, I am in awe of your knowledge…I just don't understand it.

Thanks a million,

Tricia 

Jimmy,

You are a genius; however, I am not.  I am truly grateful for every response you share; yet, I NEVER understand what you are saying.  All this death phase, effector T cells, etc. is Greek to me.  Can you please explain these things in more simplistic terms so the average (and below average…me) patients can take advantage of your advice.  Again, I am in awe of your knowledge…I just don't understand it.

Thanks a million,

Tricia 

Tricia,

I am glad you asked the question.

 It is about the biology  of a cell. A T-cell

 Death phase : The final growth phaseof the cells, during which nutrients have been depleted and cell number decreases. One of those nutrients may be IL-2.

Effector cell :a lymphocyte (as a T cell) that has been induced to differentiate into a form (as a cytotoxic T cell) capable of mounting a specific immune response called also effector lymphocyte.

There are two kind of effector cells CD4+ and CD8+ . CD4+ are know as T Helper cells. when activated, they secrete cytokines like  (IL-2). They can help activate CD8+ T-cells

 T-helper cells(also known as effector T cells or T_h cells) are a sub-group of lymphocytes (a type of white blood cell or leukocyte) that play an important role in establishing and maximizing the capabilities of the immune system.

A cytotoxic T cell (also known as T_C, CTL, T-Killer cell, cytolytic T cell, CD8+ T-cells or killer T cell) belongs to a sub-group of T lymphocytes (a type of white blood cell) that are capable of inducing the death of infected  cells or tumor cells; they kill cells that are infected with viruses (or other pathogens), or are otherwise damaged or dysfunctional

When CD-8+ T-cells are activated, they mature into (CTLs) Cytotoxic T Lymphocytes capable of distroying Melanoma Tumors.
 

You may want to download a paper I wrote called Melanoma and the Magic Bullet.

http://www.box.net/shared/kjgr6dkztj

It goes into great detail on the terminology of the the immune system

Another great reference  for Patients is the Understanding the Immune system by NCI

http://www.cancer.gov/cancertopics/understandingcancer/immunesystem

You can download a powerpoint presentation or print it as a pdf file.

I hope this helps

warm Regards

Jimmy B

Tricia,

I am glad you asked the question.

 It is about the biology  of a cell. A T-cell

 Death phase : The final growth phaseof the cells, during which nutrients have been depleted and cell number decreases. One of those nutrients may be IL-2.

Effector cell :a lymphocyte (as a T cell) that has been induced to differentiate into a form (as a cytotoxic T cell) capable of mounting a specific immune response called also effector lymphocyte.

There are two kind of effector cells CD4+ and CD8+ . CD4+ are know as T Helper cells. when activated, they secrete cytokines like  (IL-2). They can help activate CD8+ T-cells

 T-helper cells(also known as effector T cells or T_h cells) are a sub-group of lymphocytes (a type of white blood cell or leukocyte) that play an important role in establishing and maximizing the capabilities of the immune system.

A cytotoxic T cell (also known as T_C, CTL, T-Killer cell, cytolytic T cell, CD8+ T-cells or killer T cell) belongs to a sub-group of T lymphocytes (a type of white blood cell) that are capable of inducing the death of infected  cells or tumor cells; they kill cells that are infected with viruses (or other pathogens), or are otherwise damaged or dysfunctional

When CD-8+ T-cells are activated, they mature into (CTLs) Cytotoxic T Lymphocytes capable of distroying Melanoma Tumors.
 

You may want to download a paper I wrote called Melanoma and the Magic Bullet.

http://www.box.net/shared/kjgr6dkztj

It goes into great detail on the terminology of the the immune system

Another great reference  for Patients is the Understanding the Immune system by NCI

http://www.cancer.gov/cancertopics/understandingcancer/immunesystem

You can download a powerpoint presentation or print it as a pdf file.

I hope this helps

warm Regards

Jimmy B

Tricia,

I am glad you asked the question.

 It is about the biology  of a cell. A T-cell

 Death phase : The final growth phaseof the cells, during which nutrients have been depleted and cell number decreases. One of those nutrients may be IL-2.

Effector cell :a lymphocyte (as a T cell) that has been induced to differentiate into a form (as a cytotoxic T cell) capable of mounting a specific immune response called also effector lymphocyte.

There are two kind of effector cells CD4+ and CD8+ . CD4+ are know as T Helper cells. when activated, they secrete cytokines like  (IL-2). They can help activate CD8+ T-cells

 T-helper cells(also known as effector T cells or T_h cells) are a sub-group of lymphocytes (a type of white blood cell or leukocyte) that play an important role in establishing and maximizing the capabilities of the immune system.

A cytotoxic T cell (also known as T_C, CTL, T-Killer cell, cytolytic T cell, CD8+ T-cells or killer T cell) belongs to a sub-group of T lymphocytes (a type of white blood cell) that are capable of inducing the death of infected  cells or tumor cells; they kill cells that are infected with viruses (or other pathogens), or are otherwise damaged or dysfunctional

When CD-8+ T-cells are activated, they mature into (CTLs) Cytotoxic T Lymphocytes capable of distroying Melanoma Tumors.
 

You may want to download a paper I wrote called Melanoma and the Magic Bullet.

http://www.box.net/shared/kjgr6dkztj

It goes into great detail on the terminology of the the immune system

Another great reference  for Patients is the Understanding the Immune system by NCI

http://www.cancer.gov/cancertopics/understandingcancer/immunesystem

You can download a powerpoint presentation or print it as a pdf file.

I hope this helps

warm Regards

Jimmy B

Jimmy,

Thanks so much for explaining this in terms I can better understand.  I really appreciate your help and will download both papers to further educate myself.

One more question…

       What is the timing of IL-2 and Yervoy treatments that you have mentioned previously?  Which comes first…the chicken (IL-2) or the egg (yervoy)?  Also, are you more of a fan of the PD-1 now over yervoy?

I know we are all grateful that you take the time to help us with our journey, especially because you are a traveler with us!  Thanks again for your help!

Tricia

Tricia,

First, I want to tell you that took a couple of years to become fluent in the language of translational  research. I continue to learn everyday.

Now your IL2 & Yervoy  question. The timing has to do with the grow cycles of the T-cells.

Yervoy takes the brakes off the immune system and allows the T-cells to grow and multiply. In doing so, the cells need a critical amount of IL-2 to be used as a nutrient.

If HD IL-2 is introduced durn the growth and expansion phase, It causes the T-cells to shut down. It has something to do with a feed back loop to control the immune response so your body doesn't go into an autoimmune response.

If you add the HD IL-2  after the the expansion (which is aproximately 49 days or 7 weeks) the IL-2 actually Acts as a growth factor which helps maintain  functionality and survival of the T-cells. It also helps to activate the CD8+ T-cells into (CTLs) Cytotoxic T Lymphocytes.

So in my opinion,  Doing  Yervoy first makes the most sence.  I have seen some patients become  NED also by doing it in reverse IL-2 then Yervoy.

The problen with doing IL-2 first is, you may grow the unwanted T-regulator cells, (Tregs) which are a subset of the CD4+ T-cells (T-helper cells).

The reason I am a fan of anti-PD-1 therapy is two fold.

First, It blocks receptors on both the T-cells and the tumor itself. Limited data shows that it works better than Yervoy.

Secondly, the Drugs stays in the body a lot longer  with minimal decay. (about 2 months) The halflife of the drug is longer. Also the side effects seem less.

Video on T-cell activation

http://s384.photobucket.com/albums/oo290/jimmy_b/?action=view&current=TheImmuneResponse.mp4

I hope this  helps.

Jimmy B

Tricia,

First, I want to tell you that took a couple of years to become fluent in the language of translational  research. I continue to learn everyday.

Now your IL2 & Yervoy  question. The timing has to do with the grow cycles of the T-cells.

Yervoy takes the brakes off the immune system and allows the T-cells to grow and multiply. In doing so, the cells need a critical amount of IL-2 to be used as a nutrient.

If HD IL-2 is introduced durn the growth and expansion phase, It causes the T-cells to shut down. It has something to do with a feed back loop to control the immune response so your body doesn't go into an autoimmune response.

If you add the HD IL-2  after the the expansion (which is aproximately 49 days or 7 weeks) the IL-2 actually Acts as a growth factor which helps maintain  functionality and survival of the T-cells. It also helps to activate the CD8+ T-cells into (CTLs) Cytotoxic T Lymphocytes.

So in my opinion,  Doing  Yervoy first makes the most sence.  I have seen some patients become  NED also by doing it in reverse IL-2 then Yervoy.

The problen with doing IL-2 first is, you may grow the unwanted T-regulator cells, (Tregs) which are a subset of the CD4+ T-cells (T-helper cells).

The reason I am a fan of anti-PD-1 therapy is two fold.

First, It blocks receptors on both the T-cells and the tumor itself. Limited data shows that it works better than Yervoy.

Secondly, the Drugs stays in the body a lot longer  with minimal decay. (about 2 months) The halflife of the drug is longer. Also the side effects seem less.

Video on T-cell activation

http://s384.photobucket.com/albums/oo290/jimmy_b/?action=view&current=TheImmuneResponse.mp4

I hope this  helps.

Jimmy B

Jimmy,

Thanks so much for all of this information.  I am printing it all and putting it in my files.  I hope I will never need any of it, but just in case, I'll have it ready to go.  Thanks again for all of your help.  Just think of my posts as "Melanoma for Dummies."  Have a wonderful weekend!

Tricia

Jimmy,

Thanks so much for all of this information.  I am printing it all and putting it in my files.  I hope I will never need any of it, but just in case, I'll have it ready to go.  Thanks again for all of your help.  Just think of my posts as "Melanoma for Dummies."  Have a wonderful weekend!

Tricia

Tricia ,

We are on a learning curve, I just started a little earlier then you. We are all Here to educate ourselves.

Take care

Jimmy B

Tricia ,

We are on a learning curve, I just started a little earlier then you. We are all Here to educate ourselves.

Take care

Jimmy B

Tricia ,

We are on a learning curve, I just started a little earlier then you. We are all Here to educate ourselves.

Take care

Jimmy B

Jimmy,

Thanks so much for all of this information.  I am printing it all and putting it in my files.  I hope I will never need any of it, but just in case, I'll have it ready to go.  Thanks again for all of your help.  Just think of my posts as "Melanoma for Dummies."  Have a wonderful weekend!

Tricia

Tricia,

First, I want to tell you that took a couple of years to become fluent in the language of translational  research. I continue to learn everyday.

Now your IL2 & Yervoy  question. The timing has to do with the grow cycles of the T-cells.

Yervoy takes the brakes off the immune system and allows the T-cells to grow and multiply. In doing so, the cells need a critical amount of IL-2 to be used as a nutrient.

If HD IL-2 is introduced durn the growth and expansion phase, It causes the T-cells to shut down. It has something to do with a feed back loop to control the immune response so your body doesn't go into an autoimmune response.

If you add the HD IL-2  after the the expansion (which is aproximately 49 days or 7 weeks) the IL-2 actually Acts as a growth factor which helps maintain  functionality and survival of the T-cells. It also helps to activate the CD8+ T-cells into (CTLs) Cytotoxic T Lymphocytes.

So in my opinion,  Doing  Yervoy first makes the most sence.  I have seen some patients become  NED also by doing it in reverse IL-2 then Yervoy.

The problen with doing IL-2 first is, you may grow the unwanted T-regulator cells, (Tregs) which are a subset of the CD4+ T-cells (T-helper cells).

The reason I am a fan of anti-PD-1 therapy is two fold.

First, It blocks receptors on both the T-cells and the tumor itself. Limited data shows that it works better than Yervoy.

Secondly, the Drugs stays in the body a lot longer  with minimal decay. (about 2 months) The halflife of the drug is longer. Also the side effects seem less.

Video on T-cell activation

http://s384.photobucket.com/albums/oo290/jimmy_b/?action=view&current=TheImmuneResponse.mp4

I hope this  helps.

Jimmy B

Jimmy,

Thanks so much for explaining this in terms I can better understand.  I really appreciate your help and will download both papers to further educate myself.

One more question…

       What is the timing of IL-2 and Yervoy treatments that you have mentioned previously?  Which comes first…the chicken (IL-2) or the egg (yervoy)?  Also, are you more of a fan of the PD-1 now over yervoy?

I know we are all grateful that you take the time to help us with our journey, especially because you are a traveler with us!  Thanks again for your help!

Tricia

Jimmy,

Thanks so much for explaining this in terms I can better understand.  I really appreciate your help and will download both papers to further educate myself.

One more question…

       What is the timing of IL-2 and Yervoy treatments that you have mentioned previously?  Which comes first…the chicken (IL-2) or the egg (yervoy)?  Also, are you more of a fan of the PD-1 now over yervoy?

I know we are all grateful that you take the time to help us with our journey, especially because you are a traveler with us!  Thanks again for your help!

Tricia

Tricia,

   I think the main thing to get from Jimmy's IPI/IL-2 information is that there is a certain timing that is important in the sequence of events.  The exact meaning of each of the terms is something that we may have problems remembering, but as long as we get the basic idea, we can present Jimmy's data to our Onc's and look at the scheduling for the timing of the events the Onc's proposing. 

   We don't all have Jimmy's background for being able to readily assimulate many of the details, but it is grat to hve his input.  I provide much of it to my Onc's.

Tricia,

   I think the main thing to get from Jimmy's IPI/IL-2 information is that there is a certain timing that is important in the sequence of events.  The exact meaning of each of the terms is something that we may have problems remembering, but as long as we get the basic idea, we can present Jimmy's data to our Onc's and look at the scheduling for the timing of the events the Onc's proposing. 

   We don't all have Jimmy's background for being able to readily assimulate many of the details, but it is grat to hve his input.  I provide much of it to my Onc's.

Tricia,

   I think the main thing to get from Jimmy's IPI/IL-2 information is that there is a certain timing that is important in the sequence of events.  The exact meaning of each of the terms is something that we may have problems remembering, but as long as we get the basic idea, we can present Jimmy's data to our Onc's and look at the scheduling for the timing of the events the Onc's proposing. 

   We don't all have Jimmy's background for being able to readily assimulate many of the details, but it is grat to hve his input.  I provide much of it to my Onc's.

The Yevoy or PD-1 therapy would take the suppressive T regulatory cells out of play, allowing any acivated T-cells to multipy. It has been shown that if IL-2 is added during the growth phase of the t-cells could jeopardize T-cell survival.

IL-2 treatment during the expansion phase was detrimental to the survival of rapidly dividing effector T cells. In contrast,

IL-2 therapy was highly beneficial during the death phase, resulting in increased proliferation and survival of Tumor-specific T cells.

IL-2 treatment also increased proliferation of resting memory T cells in the host that controlled the disease. Tumor-specific T cells in chronically infected Host also responds to IL-2 resulting in decreased tumor burden. Thus, timing of IL-2 administration and differentiation status of the T cell are critical parameters in designing IL-2 therapies (Blattman et al., 2003).

Best regards,

Jimmy b

The Yevoy or PD-1 therapy would take the suppressive T regulatory cells out of play, allowing any acivated T-cells to multipy. It has been shown that if IL-2 is added during the growth phase of the t-cells could jeopardize T-cell survival.

IL-2 treatment during the expansion phase was detrimental to the survival of rapidly dividing effector T cells. In contrast,

IL-2 therapy was highly beneficial during the death phase, resulting in increased proliferation and survival of Tumor-specific T cells.

IL-2 treatment also increased proliferation of resting memory T cells in the host that controlled the disease. Tumor-specific T cells in chronically infected Host also responds to IL-2 resulting in decreased tumor burden. Thus, timing of IL-2 administration and differentiation status of the T cell are critical parameters in designing IL-2 therapies (Blattman et al., 2003).

Best regards,

Jimmy b