Vaccines Before Interleukin Treatment – May Boost Survival

I am starting IL2 on Feb 9th at UVA with Dr. Geoffrey Weiss.  Dr. Lipson from Hopkins fully supports IL2 but is trying to get me into a trial at NIH similar to what it talked about in this article….looks so promising.  It's always a challenge with me because I had one small brain met a year ago and also had to be on Steroids while after my pituitary gland decided it didn't care for Ipi and decided not to make Cortisol.  However, my pituitary gland recovered. 

Thank you for sharing this article….gives me so much hope!

Terrie

I am starting IL2 on Feb 9th at UVA with Dr. Geoffrey Weiss.  Dr. Lipson from Hopkins fully supports IL2 but is trying to get me into a trial at NIH similar to what it talked about in this article….looks so promising.  It's always a challenge with me because I had one small brain met a year ago and also had to be on Steroids while after my pituitary gland decided it didn't care for Ipi and decided not to make Cortisol.  However, my pituitary gland recovered. 

Thank you for sharing this article….gives me so much hope!

Terrie

I am starting IL2 on Feb 9th at UVA with Dr. Geoffrey Weiss.  Dr. Lipson from Hopkins fully supports IL2 but is trying to get me into a trial at NIH similar to what it talked about in this article….looks so promising.  It's always a challenge with me because I had one small brain met a year ago and also had to be on Steroids while after my pituitary gland decided it didn't care for Ipi and decided not to make Cortisol.  However, my pituitary gland recovered. 

Thank you for sharing this article….gives me so much hope!

Terrie

So, in the past, if you got a vaccine made for you, you had to be HLAA2 positive, which my husband isn't!! Do you know if you will need to be positive to do this treatment?? I am always interested in adding things to IL2 for longer response rates.  Valerie (Phil's wife)

My immunogenetics is pretty rusty, so I may be wrong here. However, I think that for any cancer cells to be attacked and killed by your immune system, the cancer cells must be HLA-A2 positive. Stimulating your immune system with a vaccine won't do any good. If the approach discussed in this paper gains traction, I'll go back and read up on immunogenetics again so I can share the latest information. (UGH! I find immunogenetics complex and boring.)

My immunogenetics is pretty rusty, so I may be wrong here. However, I think that for any cancer cells to be attacked and killed by your immune system, the cancer cells must be HLA-A2 positive. Stimulating your immune system with a vaccine won't do any good. If the approach discussed in this paper gains traction, I'll go back and read up on immunogenetics again so I can share the latest information. (UGH! I find immunogenetics complex and boring.)

My immunogenetics is pretty rusty, so I may be wrong here. However, I think that for any cancer cells to be attacked and killed by your immune system, the cancer cells must be HLA-A2 positive. Stimulating your immune system with a vaccine won't do any good. If the approach discussed in this paper gains traction, I'll go back and read up on immunogenetics again so I can share the latest information. (UGH! I find immunogenetics complex and boring.)

Jerry, our immune systems have a lot of different ways to attack and kill "foreign" organisms like viruses, bacteria and some types of cancer. We have antibodies, macrophages, killer T-cells and other armaments. The most effective weapon for killing melanoma is our "killer T-cells", also called "CD8+ T-cells". 

The paragraphs you pasted above are describing the ways in which various researchers have tried to increase the number of melanoma-specific killer T cells in the patient by culturing the patient's own T-cells ("autologous" means "self") with a melanoma vaccine developed from their own melanoma cells. Then they put the cultured cells back into the patient with additional vaccination of the patient in the hopes of killing the melanoma. 

The trick is that the immune system is a little more complex than that (well, OK, a lot more complex than that). The interaction between killer T cells and cancer cells is like Velcro. Velcro comes as two strips; one strip is covered in hooks and the other strip is covered with loops. When you put the two strips of velcro together, they stick. Killer T cells are covered with hooks, target cancer cells are covered with loops called HLA-A2. You need both to get the killer cells to stick to and kill the cancer. If one's cancer cells do not have the HLA-A2 protein on their surface, the killer cells will not work no matter how many there are.

As a somewhat hair-raising side note, I recall reading some papers that say that melanoma can actually stop producing HLA-A2 so as to deliberately evade immune attack.  Scarey to think about.

Jerry, our immune systems have a lot of different ways to attack and kill "foreign" organisms like viruses, bacteria and some types of cancer. We have antibodies, macrophages, killer T-cells and other armaments. The most effective weapon for killing melanoma is our "killer T-cells", also called "CD8+ T-cells". 

The paragraphs you pasted above are describing the ways in which various researchers have tried to increase the number of melanoma-specific killer T cells in the patient by culturing the patient's own T-cells ("autologous" means "self") with a melanoma vaccine developed from their own melanoma cells. Then they put the cultured cells back into the patient with additional vaccination of the patient in the hopes of killing the melanoma. 

The trick is that the immune system is a little more complex than that (well, OK, a lot more complex than that). The interaction between killer T cells and cancer cells is like Velcro. Velcro comes as two strips; one strip is covered in hooks and the other strip is covered with loops. When you put the two strips of velcro together, they stick. Killer T cells are covered with hooks, target cancer cells are covered with loops called HLA-A2. You need both to get the killer cells to stick to and kill the cancer. If one's cancer cells do not have the HLA-A2 protein on their surface, the killer cells will not work no matter how many there are.

As a somewhat hair-raising side note, I recall reading some papers that say that melanoma can actually stop producing HLA-A2 so as to deliberately evade immune attack.  Scarey to think about.

Okay, all this stuff is way over my head!!  All I know for sure, is that I got depressed when I first found out that Phil was HLAA2 negative, thinking he wouldn't responded to as many treatments, and he would have less options!  However, Phil has had a wonderful response so far to TIL and his fighting T cells, still stable 20 months later! In Houston, TIL includes two full rounds of High Dose IL2. Wish we all knew the magic bullet!  Thanks for the information!  Valerie

Okay, all this stuff is way over my head!!  All I know for sure, is that I got depressed when I first found out that Phil was HLAA2 negative, thinking he wouldn't responded to as many treatments, and he would have less options!  However, Phil has had a wonderful response so far to TIL and his fighting T cells, still stable 20 months later! In Houston, TIL includes two full rounds of High Dose IL2. Wish we all knew the magic bullet!  Thanks for the information!  Valerie

OK, Valerie, your intriguing post made me go back and brush up on my immunogenetics. First off, let me say that I am delilghted that Phil is having such a good response to TIL. Second, I am pleased to stand corrected in regards to HLA-A2, especially when the correction involves such a happy outcome.

As I expected, there has been a lot of progress in immunogenetics in the years since I was active in the field. HLA-A2 was the first (and is still the most important) gene identified that allows T-cells to kill melanoma. But now researchers know that there are several other, related genes that do that, too. One called HLA-C3 is just as good as HLA-A2. 

So the bottom line for us is that your HLA type does affect your responsiveness to melanoma vaccines or to the TIL procedure, you do NOT have to be HLA-A2 positive– a few other types will work, too. Of course, Valerie and Phil could have told you that already. 😉

OK, Valerie, your intriguing post made me go back and brush up on my immunogenetics. First off, let me say that I am delilghted that Phil is having such a good response to TIL. Second, I am pleased to stand corrected in regards to HLA-A2, especially when the correction involves such a happy outcome.

As I expected, there has been a lot of progress in immunogenetics in the years since I was active in the field. HLA-A2 was the first (and is still the most important) gene identified that allows T-cells to kill melanoma. But now researchers know that there are several other, related genes that do that, too. One called HLA-C3 is just as good as HLA-A2. 

So the bottom line for us is that your HLA type does affect your responsiveness to melanoma vaccines or to the TIL procedure, you do NOT have to be HLA-A2 positive– a few other types will work, too. Of course, Valerie and Phil could have told you that already. 😉

OK, Valerie, your intriguing post made me go back and brush up on my immunogenetics. First off, let me say that I am delilghted that Phil is having such a good response to TIL. Second, I am pleased to stand corrected in regards to HLA-A2, especially when the correction involves such a happy outcome.

As I expected, there has been a lot of progress in immunogenetics in the years since I was active in the field. HLA-A2 was the first (and is still the most important) gene identified that allows T-cells to kill melanoma. But now researchers know that there are several other, related genes that do that, too. One called HLA-C3 is just as good as HLA-A2. 

So the bottom line for us is that your HLA type does affect your responsiveness to melanoma vaccines or to the TIL procedure, you do NOT have to be HLA-A2 positive– a few other types will work, too. Of course, Valerie and Phil could have told you that already. 😉

Okay, all this stuff is way over my head!!  All I know for sure, is that I got depressed when I first found out that Phil was HLAA2 negative, thinking he wouldn't responded to as many treatments, and he would have less options!  However, Phil has had a wonderful response so far to TIL and his fighting T cells, still stable 20 months later! In Houston, TIL includes two full rounds of High Dose IL2. Wish we all knew the magic bullet!  Thanks for the information!  Valerie

Jerry, our immune systems have a lot of different ways to attack and kill "foreign" organisms like viruses, bacteria and some types of cancer. We have antibodies, macrophages, killer T-cells and other armaments. The most effective weapon for killing melanoma is our "killer T-cells", also called "CD8+ T-cells". 

The paragraphs you pasted above are describing the ways in which various researchers have tried to increase the number of melanoma-specific killer T cells in the patient by culturing the patient's own T-cells ("autologous" means "self") with a melanoma vaccine developed from their own melanoma cells. Then they put the cultured cells back into the patient with additional vaccination of the patient in the hopes of killing the melanoma. 

The trick is that the immune system is a little more complex than that (well, OK, a lot more complex than that). The interaction between killer T cells and cancer cells is like Velcro. Velcro comes as two strips; one strip is covered in hooks and the other strip is covered with loops. When you put the two strips of velcro together, they stick. Killer T cells are covered with hooks, target cancer cells are covered with loops called HLA-A2. You need both to get the killer cells to stick to and kill the cancer. If one's cancer cells do not have the HLA-A2 protein on their surface, the killer cells will not work no matter how many there are.

As a somewhat hair-raising side note, I recall reading some papers that say that melanoma can actually stop producing HLA-A2 so as to deliberately evade immune attack.  Scarey to think about.

So, in the past, if you got a vaccine made for you, you had to be HLAA2 positive, which my husband isn't!! Do you know if you will need to be positive to do this treatment?? I am always interested in adding things to IL2 for longer response rates.  Valerie (Phil's wife)

So, in the past, if you got a vaccine made for you, you had to be HLAA2 positive, which my husband isn't!! Do you know if you will need to be positive to do this treatment?? I am always interested in adding things to IL2 for longer response rates.  Valerie (Phil's wife)

You are absolutely correct, Celeste. The sentence you quoted was ill-concieved and poorly written and could well give people the wrong message. The immune system has a lot of different pathways it can use to attack and kill melanoma cells– HLA-A2 relates to only one or a few of those pathways. And, as I said above, I now know that there are other HLA antigens that are effective with melanoma vaccines, too. 

Immunogenetics is a very complex field and researchers are learning more about it all the time. It is a challenge to share information on this forum so that people can understand what is going on without overwhelming them with jargon or inadvertent misinformation. That's why it's good to have several people reading and responding to each other's posts. Two (or 3 or 4) heads are better than one.

You are absolutely correct, Celeste. The sentence you quoted was ill-concieved and poorly written and could well give people the wrong message. The immune system has a lot of different pathways it can use to attack and kill melanoma cells– HLA-A2 relates to only one or a few of those pathways. And, as I said above, I now know that there are other HLA antigens that are effective with melanoma vaccines, too. 

Immunogenetics is a very complex field and researchers are learning more about it all the time. It is a challenge to share information on this forum so that people can understand what is going on without overwhelming them with jargon or inadvertent misinformation. That's why it's good to have several people reading and responding to each other's posts. Two (or 3 or 4) heads are better than one.

You are absolutely correct, Celeste. The sentence you quoted was ill-concieved and poorly written and could well give people the wrong message. The immune system has a lot of different pathways it can use to attack and kill melanoma cells– HLA-A2 relates to only one or a few of those pathways. And, as I said above, I now know that there are other HLA antigens that are effective with melanoma vaccines, too. 

Immunogenetics is a very complex field and researchers are learning more about it all the time. It is a challenge to share information on this forum so that people can understand what is going on without overwhelming them with jargon or inadvertent misinformation. That's why it's good to have several people reading and responding to each other's posts. Two (or 3 or 4) heads are better than one.