› Forums › General Melanoma Community › Question – why do they test for HLA?
- This topic has 18 replies, 6 voices, and was last updated 12 years, 8 months ago by
MariaH.
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- August 12, 2011 at 1:33 am
As I mentioned previously, Dave went down to NIH and did not qualify for their TIL study. However, they did test him for HLA – which I know was to see if he qualified for the ESO and MAGE trials. However, I don't understand what purpose HLA has in melanoma treatment. I know for the ESO and MAGE trials, they extracted the white blood cells from your blood stream, which is different then the TIL study (they use actual tumor). He tested negative, which the nurse said is just "genetics". But I am curious – what role does it play?
As I mentioned previously, Dave went down to NIH and did not qualify for their TIL study. However, they did test him for HLA – which I know was to see if he qualified for the ESO and MAGE trials. However, I don't understand what purpose HLA has in melanoma treatment. I know for the ESO and MAGE trials, they extracted the white blood cells from your blood stream, which is different then the TIL study (they use actual tumor). He tested negative, which the nurse said is just "genetics". But I am curious – what role does it play?
Thank you, as always….
Maria
- Replies
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- August 12, 2011 at 3:01 am
Maria. I can only tell the little I know, my husband also tested negative for HLA-02, which I believe is a protein found in your blood. I was told that this test has nothing to do with having melanoma or any specific type of mutation, simply the protein is present or not. I think it’s a 50 percent odds. Not having HLA-02 protein in your blood excludes you from most of the vaccine trials. now, when I am reading trials, I go first to the inclusion/exclusion sections, and frequently it will say need to be HLA-02 positive. One more thing I can’t control, so I move on. Good luck with the radiation and IL2. Valerie (phil’s wife) -
- August 12, 2011 at 3:01 am
Maria. I can only tell the little I know, my husband also tested negative for HLA-02, which I believe is a protein found in your blood. I was told that this test has nothing to do with having melanoma or any specific type of mutation, simply the protein is present or not. I think it’s a 50 percent odds. Not having HLA-02 protein in your blood excludes you from most of the vaccine trials. now, when I am reading trials, I go first to the inclusion/exclusion sections, and frequently it will say need to be HLA-02 positive. One more thing I can’t control, so I move on. Good luck with the radiation and IL2. Valerie (phil’s wife) -
- August 12, 2011 at 3:05 am
Maria, I found the following info about HLA:
http://www.asco.org/ASCOv2/Meetings/Abstracts?&vmview=abst_detail_view&confID=40&abstractID=32435
and
http://en.wikipedia.org/wiki/Human_leukocyte_antigen#In_cancer
see also
http://www.springerlink.com/content/b761785101268365/As the nurse said – it is all about genetics.
Best wishes
Frank from Australia
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- August 12, 2011 at 3:05 am
Maria, I found the following info about HLA:
http://www.asco.org/ASCOv2/Meetings/Abstracts?&vmview=abst_detail_view&confID=40&abstractID=32435
and
http://en.wikipedia.org/wiki/Human_leukocyte_antigen#In_cancer
see also
http://www.springerlink.com/content/b761785101268365/As the nurse said – it is all about genetics.
Best wishes
Frank from Australia
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- August 12, 2011 at 3:06 am
It's kinda complicated, so I will kepp it short.
I'm not a doctor either, so you still may have to have a doctor help explain this as I may not be totally accurate.
HLA typing; Definition
A histocompatibility antigen blood test looks at proteins called human leukocyte antigens (HLAs), which are found on the surface of nearly every cell in the human body. HLAs are found in large amounts on the surface of white blood cells. They help the immune system tell the difference between body tissue and foreign substances.
Adoptive cell transfer therapy (ACT) is where testing may be performed for the correct HLA type. If positive for the HLA type, these specific t-cells are then harvested, amplified and returned to the body.
Michael
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- August 12, 2011 at 3:32 am
Just to clarify, what little I know, you can be HLA-02 negative and still qualify for TIL(adoptive cell transfer), both NIH and MD Anderson have these programs going on now that accept HLA-02 negative. I believe David wasn’t accept at NIH for adoptive cell because the surgery for tumor removal was too difficult at this time, so know that is an option for the future. HLA-02 status is more exclusive in the vaccine trials, like dendritic cell,etc. Valerie (Phil’s wife) -
- August 12, 2011 at 3:32 am
Just to clarify, what little I know, you can be HLA-02 negative and still qualify for TIL(adoptive cell transfer), both NIH and MD Anderson have these programs going on now that accept HLA-02 negative. I believe David wasn’t accept at NIH for adoptive cell because the surgery for tumor removal was too difficult at this time, so know that is an option for the future. HLA-02 status is more exclusive in the vaccine trials, like dendritic cell,etc. Valerie (Phil’s wife)
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- August 12, 2011 at 3:06 am
It's kinda complicated, so I will kepp it short.
I'm not a doctor either, so you still may have to have a doctor help explain this as I may not be totally accurate.
HLA typing; Definition
A histocompatibility antigen blood test looks at proteins called human leukocyte antigens (HLAs), which are found on the surface of nearly every cell in the human body. HLAs are found in large amounts on the surface of white blood cells. They help the immune system tell the difference between body tissue and foreign substances.
Adoptive cell transfer therapy (ACT) is where testing may be performed for the correct HLA type. If positive for the HLA type, these specific t-cells are then harvested, amplified and returned to the body.
Michael
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- August 12, 2011 at 4:41 am
HLA is basically for tissue typing. Many clinical trials are restricted to certain HLA’s to help define what effect the treatment has on a definite more common set of people. I’m the wrong type HLA to qualify for many trials. I believe HLA-A201 is the one they want most often. I will try to post a few URL’s after getting back to my computer. -
- August 12, 2011 at 4:41 am
HLA is basically for tissue typing. Many clinical trials are restricted to certain HLA’s to help define what effect the treatment has on a definite more common set of people. I’m the wrong type HLA to qualify for many trials. I believe HLA-A201 is the one they want most often. I will try to post a few URL’s after getting back to my computer. -
- August 12, 2011 at 11:09 am
Thank you all so much for responding. Hopefully, Dave will be a responder to IL-2 and we won't have to look any further for treatment options… but it's always good to have a backup plan, and now I know what to look into.
Best wishes to all of you,
Maria
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- August 12, 2011 at 7:11 pm
Hi Maria
Sorry I haven't responded earlier but I had a 10-day respite, most of which I took up north at our cottage…I go back on Tuesday, August 16th to NIH for the big guns! I will be there until about September 8th. I'm sorry to hear that Dave had such rapid growth but radiation should do its work and then on to IL-2. I pray he will be an excellent responder.
Linda asked me to check about HLA status while I was done at Bethesda. They plan to have a TIL trial coming up that does not require you to be HLA 0201 positive. One patient has done the procedure and they are waiting for his results, I will check when I get down there to see if anything has developed. The new treatement option will be called ECCE (that too I will confirm). Val xx
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- August 12, 2011 at 9:21 pm
I'm so glad to hear that you got to take a nice break from the all medical mumbo jumbo. Lord knows, it takes a toll and a little normalcy is good for the soul.
I'd like to say that it is nice to have someone "on the inside", but I'd rather nobody was in this situation. Keep me posted on the patients response – it would be interesting to see how he does.
I am really hoping that the IL-2 will do the trick for Dave – if not, at least we have NIH in our back pocket.
I so hope everything goes well for you. You are certainly in good hands down there – we liked everybody we met, and I don't think you could ask for a better team of medical professionals.
All our best to you Val, and we'll be thinking of you. Keep in touch if you can.
Maria
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- August 12, 2011 at 9:21 pm
I'm so glad to hear that you got to take a nice break from the all medical mumbo jumbo. Lord knows, it takes a toll and a little normalcy is good for the soul.
I'd like to say that it is nice to have someone "on the inside", but I'd rather nobody was in this situation. Keep me posted on the patients response – it would be interesting to see how he does.
I am really hoping that the IL-2 will do the trick for Dave – if not, at least we have NIH in our back pocket.
I so hope everything goes well for you. You are certainly in good hands down there – we liked everybody we met, and I don't think you could ask for a better team of medical professionals.
All our best to you Val, and we'll be thinking of you. Keep in touch if you can.
Maria
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- August 12, 2011 at 7:11 pm
Hi Maria
Sorry I haven't responded earlier but I had a 10-day respite, most of which I took up north at our cottage…I go back on Tuesday, August 16th to NIH for the big guns! I will be there until about September 8th. I'm sorry to hear that Dave had such rapid growth but radiation should do its work and then on to IL-2. I pray he will be an excellent responder.
Linda asked me to check about HLA status while I was done at Bethesda. They plan to have a TIL trial coming up that does not require you to be HLA 0201 positive. One patient has done the procedure and they are waiting for his results, I will check when I get down there to see if anything has developed. The new treatement option will be called ECCE (that too I will confirm). Val xx
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- August 12, 2011 at 11:09 am
Thank you all so much for responding. Hopefully, Dave will be a responder to IL-2 and we won't have to look any further for treatment options… but it's always good to have a backup plan, and now I know what to look into.
Best wishes to all of you,
Maria
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- August 12, 2011 at 7:54 pm
http://cancerres.aacrjournals.org/content/52/23/6561.abstract
HLA Association with Response and Toxicity in Melanoma Patients Treated with Interleukin 2-based Immunotherapy
- Francesco M. Marincola1,
- David Venzon,
- Donald White,
- Joshua T. Rubin,
- Michael T. Lotze,
- Toni B. Simonis,
- Jaikrishna Balkissoon,
- Steven A. Rosenberg, and
- David R. Parkinson
+ Author Affiliations
Surgery Branch, Clinical Oncology Program, Division of Cancer Treatment [F. M. M., D. W., J. B., S. A. R., D. R. P.] and Biostatistics and Data Management Section [D. V.], National Cancer Institute, and Department of Transfusion Medicine [T. B. S.], NIH, Bethesda, Maryland 20892, and Department of Surgery, University of Pittsburgh [J. T. R., M. T. L.], Pittsburgh, Pennsylvania 15261
- 1To whom requests for reprints should be addressed, at the Surgery Branch, National Cancer Institute, Building 10, Room 2B42, Bethesda, MD 20892.
Abstract
Peripheral blood lymphocytes from 146 patients with metastatic melanoma undergoing interleukin 2 (IL-2)-based immunotherapy were characterized for HLA A, B, Cw, DR, DQw, and DRw specificities. Patients had been enrolled into sequential treatment protocols with either IL-2 alone (28) or in combination with tumor-infiltrating lymphocytes (TILs) (86), α-interferon (26), lymphokine-activated killer cells (16), radiation therapy (7), cyclophosphamide (3), tumor necrosis factor (1), and interleukin 4 (1) for a total of 168 courses of therapy. HLA phenotype was then correlated with response rate and toxicity to IL-2. We noted: (a) a significant difference in the frequency of A11 (20.5% versus 10.2%; P < 0.05) allele between melanoma patients and the North American Caucasian population; (b) a significantly higher frequency of A11 phenotype among responders (40.5%) than in the melanoma patient population (20.5%; P < 0.01), which was even more obvious among patients responding to TIL therapy (47.4% versus 22.1%; P < 0.05); within TIL patients, responders also had an increased frequency of A19 (42.1% versus 25.6%; P < 0.05); (c) a correlation between the number of TILs received and response rate (P < 0.005); and (d) an association between DR4 haplotype and decreased tolerance to IL-2 among the patients receiving TILs (P = 0.01). These results suggest that, in melanoma patients, some HLA Class I specificities may predict for a greater likelihood of response to IL-2-based therapy, while HLA Class II phenotype correlates with tolerance to the combination of TIL and IL-2 therapy.
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- August 12, 2011 at 7:54 pm
http://cancerres.aacrjournals.org/content/52/23/6561.abstract
HLA Association with Response and Toxicity in Melanoma Patients Treated with Interleukin 2-based Immunotherapy
- Francesco M. Marincola1,
- David Venzon,
- Donald White,
- Joshua T. Rubin,
- Michael T. Lotze,
- Toni B. Simonis,
- Jaikrishna Balkissoon,
- Steven A. Rosenberg, and
- David R. Parkinson
+ Author Affiliations
Surgery Branch, Clinical Oncology Program, Division of Cancer Treatment [F. M. M., D. W., J. B., S. A. R., D. R. P.] and Biostatistics and Data Management Section [D. V.], National Cancer Institute, and Department of Transfusion Medicine [T. B. S.], NIH, Bethesda, Maryland 20892, and Department of Surgery, University of Pittsburgh [J. T. R., M. T. L.], Pittsburgh, Pennsylvania 15261
- 1To whom requests for reprints should be addressed, at the Surgery Branch, National Cancer Institute, Building 10, Room 2B42, Bethesda, MD 20892.
Abstract
Peripheral blood lymphocytes from 146 patients with metastatic melanoma undergoing interleukin 2 (IL-2)-based immunotherapy were characterized for HLA A, B, Cw, DR, DQw, and DRw specificities. Patients had been enrolled into sequential treatment protocols with either IL-2 alone (28) or in combination with tumor-infiltrating lymphocytes (TILs) (86), α-interferon (26), lymphokine-activated killer cells (16), radiation therapy (7), cyclophosphamide (3), tumor necrosis factor (1), and interleukin 4 (1) for a total of 168 courses of therapy. HLA phenotype was then correlated with response rate and toxicity to IL-2. We noted: (a) a significant difference in the frequency of A11 (20.5% versus 10.2%; P < 0.05) allele between melanoma patients and the North American Caucasian population; (b) a significantly higher frequency of A11 phenotype among responders (40.5%) than in the melanoma patient population (20.5%; P < 0.01), which was even more obvious among patients responding to TIL therapy (47.4% versus 22.1%; P < 0.05); within TIL patients, responders also had an increased frequency of A19 (42.1% versus 25.6%; P < 0.05); (c) a correlation between the number of TILs received and response rate (P < 0.005); and (d) an association between DR4 haplotype and decreased tolerance to IL-2 among the patients receiving TILs (P = 0.01). These results suggest that, in melanoma patients, some HLA Class I specificities may predict for a greater likelihood of response to IL-2-based therapy, while HLA Class II phenotype correlates with tolerance to the combination of TIL and IL-2 therapy.
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