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Whole Cell Cytometric profiling?? Answer from the lab
Whole Cell Cytometric profiling is when living cancer cells obtained from each patient actually are exposed to dozens of candidate chemotherapy drugs and the true cell killing ability of each drug is precisely measured. Then the right combination of drugs are then used in your own treatment, since it is proven to "kill" your cancer cells. Has anyone out there had this done? I know there are two companies out in California that perform this service. You have to send them samples of your cancer cells and then they conduct this testing on your cells. It is completely different than gene testing. Seems that most institutions have their own "cocktail" that they use on everybody in a clinical trial. Would seem smart to have your own cells tested to know what will work in your own body before going through these serious treatments.
Last edited by jk60 on Wed Feb 06, 2013 8:28 pm, edited 1 time in total.
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jk60 - Name: jk
Re: Whole Cell Cytometric profiling?? Has anyone done this?
Hello JK,
From what I know the idea of in vitro sensitivity testing for cancer (which really is what you are talking about) has been around for a while and can be useful for some diseases. Mostly I've read about human solid tumors like breast cancer for example. Unfortunately most myeloma cells are particularly sensitive to their surroundings in the bone marrow and will die within a few hours when removed. The exception might be plasma cell leukemia which is advanced myeloma that has developed the ability to survive outside the marrow in the blood.
Because of that I doubt these companies offer their service for myeloma patients. They would have to develop a cell line from your specimen and there is the risk that they select for a very rare, atypical subpopulation of cells that are somehow able grow in culture but may not accurately reflect most of your cells or their response to the drugs.
I have heard of a nude (immunocompromised) mouse model where they inject fragments of human bone with marrow and myeloma cells under the skin and test drugs but these are very complex and expensive studies usually done by pharmaceutical companies for their own drugs. The human myeloma cells stay in the graft but the human antibodies produced by the myeloma can be monitored in the mouse blood. Its an indirect measurement. Also, since the mice are immunosuppressed these studies cannot analyze the immune modulating drugs.
It might be worth talking to these companies but I'd ask them these questions-
1) How successful are you in generating enough myeloma cells from individual patients for your tests? Will I be charged if my cells do not grow in culture?
2) What model do you use? If in plastic flasks how do you attempt to recreate the bone marrow environment? If in the mouse will this preclude immunomodulatory drugs?
3) Can you assure me the resulting cells accurately reflect the original cells sent to you?
JK- It would be very smart to use your own cancer cells to lead you to the right choice of treatment. Unfortunately, right now the science hasn't caught up with the technical challenges in myeloma.
Maybe someday when we learn more about the relationship between myeloma and the bone marrow we can recreate the system, grow the cancer cells and test different drug combos. Most importantly, this same knowledge will also lead to better drugs to treat myeloma since its clear that there is something crucial in the bone marrow without which myeloma cells die.
Wouldn't it be great to learn what these crucial elements are so we could block them and one day maybe cure this terrible disease.
I'd be curious to hear what they say if you look into this question further.
All my best to you,
Dan
From what I know the idea of in vitro sensitivity testing for cancer (which really is what you are talking about) has been around for a while and can be useful for some diseases. Mostly I've read about human solid tumors like breast cancer for example. Unfortunately most myeloma cells are particularly sensitive to their surroundings in the bone marrow and will die within a few hours when removed. The exception might be plasma cell leukemia which is advanced myeloma that has developed the ability to survive outside the marrow in the blood.
Because of that I doubt these companies offer their service for myeloma patients. They would have to develop a cell line from your specimen and there is the risk that they select for a very rare, atypical subpopulation of cells that are somehow able grow in culture but may not accurately reflect most of your cells or their response to the drugs.
I have heard of a nude (immunocompromised) mouse model where they inject fragments of human bone with marrow and myeloma cells under the skin and test drugs but these are very complex and expensive studies usually done by pharmaceutical companies for their own drugs. The human myeloma cells stay in the graft but the human antibodies produced by the myeloma can be monitored in the mouse blood. Its an indirect measurement. Also, since the mice are immunosuppressed these studies cannot analyze the immune modulating drugs.
It might be worth talking to these companies but I'd ask them these questions-
1) How successful are you in generating enough myeloma cells from individual patients for your tests? Will I be charged if my cells do not grow in culture?
2) What model do you use? If in plastic flasks how do you attempt to recreate the bone marrow environment? If in the mouse will this preclude immunomodulatory drugs?
3) Can you assure me the resulting cells accurately reflect the original cells sent to you?
JK- It would be very smart to use your own cancer cells to lead you to the right choice of treatment. Unfortunately, right now the science hasn't caught up with the technical challenges in myeloma.
Maybe someday when we learn more about the relationship between myeloma and the bone marrow we can recreate the system, grow the cancer cells and test different drug combos. Most importantly, this same knowledge will also lead to better drugs to treat myeloma since its clear that there is something crucial in the bone marrow without which myeloma cells die.
Wouldn't it be great to learn what these crucial elements are so we could block them and one day maybe cure this terrible disease.
I'd be curious to hear what they say if you look into this question further.
All my best to you,
Dan
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Dan in Phoenix
Re: Whole Cell Cytometric profiling?? Has anyone done this?
Dan,
Thanks for your very detailed reply. As I look into this, will let you know what I find out.
JK
Thanks for your very detailed reply. As I look into this, will let you know what I find out.
JK
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jk60 - Name: jk
Re: Whole Cell Cytometric profiling?? Has anyone done this?
Dan,
I sent your feedback to my questions to one of the services and wanted to send you their answers on the points you raised. I'm just not sure that many people are informed of this option. They actually sent me two lab reports done for myleoma patients.. One that had never received treatment and the other had already received treatment. It was interesting to see how the lab work showed which drugs their individual cells were sensitive to...especially with prior treatments. Just thought that you and others might want to know about this.
JK
Dan's Feedback:
From what I know the idea of in vitro sensitivity testing for cancer (which really is what you are talking about) has been around for a while and can be useful for some diseases. Mostly I've read about human solid tumors like breast cancer for example. Unfortunately most myeloma cells are particularly sensitive to their surroundings in the bone marrow and will die within a few hours when removed. The exception might be plasma cell leukemia which is advanced myeloma that has developed the ability to survive outside the marrow in the blood.
Lab Feedback
The process of programmed cell death requires 72-96 hrs. As such, myeloma cells can indeed be evaluated for the differential effect of drug exposure during the 72-96 hour window. We have successfully conducted 100's of studies on hematologic neoplasms, many of them myelomas, and among our observations was the identification of multiple myeloma for Bortezomib and Bortezomib for mantle cell lymphoma, all in collaboration with Millennium pharmaceuticals before Bortezomib's approval by the FDA.
Dan's Feedback:
Because of that I doubt these companies offer their service for myeloma patients. They would have to develop a cell line from your specimen and there is the risk that they select for a very rare, atypical subpopulation of cells that are somehow able grow in culture but may not accurately reflect most of your cells or their response to the drugs.
Lab Feedback:
We never use cell lines. These are primary culture studies using each patient’s unique cells to identify drug activity.
Dan's Feedback:
I have heard of a nude (immunocompromised) mouse model where they inject fragments of human bone with marrow and myeloma cells under the skin and test drugs but these are very complex and expensive studies usually done by pharmaceutical companies for their own drugs. The human myeloma cells stay in the graft but the human antibodies produced by the myeloma can be monitored in the mouse blood. Its an indirect measurement. Also, since the mice are immunosuppressed these studies cannot analyze the immune modulating drugs.
Lab Feedback
Some classes of agents are not readily evaluated in this model. While thalidomide has relatively little cytotoxic effect, the imid lenalidomide is actually cytotoxic and can be tested in vitro.
It might be worth talking to these companies but I'd ask them these
questions-
1) How successful are you in generating enough myeloma cells from individual patients for your tests? Will I be charged if my cells do not grow in culture?
Lab Answer
We isolate myeloma cells from the bone marrow; we DO NOT propagate them.(ie they do not grow them!!) As you are aware a single aspirate of myeloma from a bone marrow sample can provide billions of myeloma cells. If we receive a bone marrow aspirate that does provide the quantity/quality of myeloma cells required for our analysis, there will be a $500 laboratory processing fee to cover transportation, certified laboratory technician time, laboratory supplies, etc.
2) What model do you use? If in plastic flasks how do you attempt to recreate the bone marrow environment? If in the mouse will this preclude immunomodulatory drugs?
Lab Answer
The cells are in suspension culture with a very short period of observation. Again, certain classes of drugs cannot be readily tested.
3) Can you assure me the resulting cells accurately reflect the original cells sent to you?
Lab Answer
In a meta-analysis submitted to ASCO on February 5, 2013, including both solid and hematologic neoplasms, the laboratory directed populations reveal a 2.04 fold superior outcome when drugs are selected in vitro (P = 0.001). The receiver operator curve has a AUC of .89. Few laboratory tests of any kind in use today can match these performance characteristics.
I sent your feedback to my questions to one of the services and wanted to send you their answers on the points you raised. I'm just not sure that many people are informed of this option. They actually sent me two lab reports done for myleoma patients.. One that had never received treatment and the other had already received treatment. It was interesting to see how the lab work showed which drugs their individual cells were sensitive to...especially with prior treatments. Just thought that you and others might want to know about this.
JK
Dan's Feedback:
From what I know the idea of in vitro sensitivity testing for cancer (which really is what you are talking about) has been around for a while and can be useful for some diseases. Mostly I've read about human solid tumors like breast cancer for example. Unfortunately most myeloma cells are particularly sensitive to their surroundings in the bone marrow and will die within a few hours when removed. The exception might be plasma cell leukemia which is advanced myeloma that has developed the ability to survive outside the marrow in the blood.
Lab Feedback
The process of programmed cell death requires 72-96 hrs. As such, myeloma cells can indeed be evaluated for the differential effect of drug exposure during the 72-96 hour window. We have successfully conducted 100's of studies on hematologic neoplasms, many of them myelomas, and among our observations was the identification of multiple myeloma for Bortezomib and Bortezomib for mantle cell lymphoma, all in collaboration with Millennium pharmaceuticals before Bortezomib's approval by the FDA.
Dan's Feedback:
Because of that I doubt these companies offer their service for myeloma patients. They would have to develop a cell line from your specimen and there is the risk that they select for a very rare, atypical subpopulation of cells that are somehow able grow in culture but may not accurately reflect most of your cells or their response to the drugs.
Lab Feedback:
We never use cell lines. These are primary culture studies using each patient’s unique cells to identify drug activity.
Dan's Feedback:
I have heard of a nude (immunocompromised) mouse model where they inject fragments of human bone with marrow and myeloma cells under the skin and test drugs but these are very complex and expensive studies usually done by pharmaceutical companies for their own drugs. The human myeloma cells stay in the graft but the human antibodies produced by the myeloma can be monitored in the mouse blood. Its an indirect measurement. Also, since the mice are immunosuppressed these studies cannot analyze the immune modulating drugs.
Lab Feedback
Some classes of agents are not readily evaluated in this model. While thalidomide has relatively little cytotoxic effect, the imid lenalidomide is actually cytotoxic and can be tested in vitro.
It might be worth talking to these companies but I'd ask them these
questions-
1) How successful are you in generating enough myeloma cells from individual patients for your tests? Will I be charged if my cells do not grow in culture?
Lab Answer
We isolate myeloma cells from the bone marrow; we DO NOT propagate them.(ie they do not grow them!!) As you are aware a single aspirate of myeloma from a bone marrow sample can provide billions of myeloma cells. If we receive a bone marrow aspirate that does provide the quantity/quality of myeloma cells required for our analysis, there will be a $500 laboratory processing fee to cover transportation, certified laboratory technician time, laboratory supplies, etc.
2) What model do you use? If in plastic flasks how do you attempt to recreate the bone marrow environment? If in the mouse will this preclude immunomodulatory drugs?
Lab Answer
The cells are in suspension culture with a very short period of observation. Again, certain classes of drugs cannot be readily tested.
3) Can you assure me the resulting cells accurately reflect the original cells sent to you?
Lab Answer
In a meta-analysis submitted to ASCO on February 5, 2013, including both solid and hematologic neoplasms, the laboratory directed populations reveal a 2.04 fold superior outcome when drugs are selected in vitro (P = 0.001). The receiver operator curve has a AUC of .89. Few laboratory tests of any kind in use today can match these performance characteristics.
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jk60 - Name: jk
Re: Whole Cell Cytometric profiling?? Has anyone done this?
Hi JK,
Thanks for the very interesting and informative feedback from the lab and for providing their actual answers. The ASCO abstract is most convincing because without these kinds of studies the results are purely academic. They don't break out their multiple myeloma patients but as you note they only analyzed two.
Their responses seem reasonable since they do a short term culture only. I know from professional experience that there are often excess cells left over from diagnostic biopsies- especially relapse or active disease. As a patient I know first hand how difficult BM biopsies can be- I truly hate them- and the pain they can cause.
I was working in a cutting edge molecular pathology lab at Georgetown's Lombardi CC after my diagnosis and actually set up a ~1500 specimen tumor bank from EXCESS tissue. Mostly BM but also blood, lymph nodes ect. The bank actually benefited the patients because as new tests came on-board we could thaw their original samples and test them to see if they originally had certain markers or gene expression.
This was before HIPPA and the rules were more relaxed. Many of our patients were kids with leukemia. In the 1980s and we were just on the cusp of curing most patients. I treated their specimens as "solid gold"- hoping that this was going to be the only chance to capture their diseased cells because chances were good they would be treated, not relapse and be cured of their disease.
Every patient (or parent) signed an agreement that their tissues could be used for research. Today patients have to consent for specific studies so my tumor bank would need to be de-identified to be useful. I think this is fair so patients know exactly what is done with their tissue.
I think this is one reason why patients who go to the top meyeloma centers with active research programs can often get the best treatments and result. Their excess specimens can be used for research instead of simply being thrown away.
AGAIN, DIAGNOSIS IS THE FIRST PRIORITY, ONLY AGREE TO PROVIDE TISSUE THAT IS EXCESS-NOT NEEDED. I don't know about you but the idea of wasting a million or more of my cells is not efficient and doesn't help anyone.
JK- for me this thread has opened up an interesting issue for multiple myeloma patients. As active participants in our care we should ask our doctors what research can be done with any excess diagnostic tissue from our biopsies. The best centers have their own studies but patients like you can also select their own uses for excess tissues. I know that I have had tissue sent to a specialty genetics lab and been very pleased that I did- it provided me and my doctors with important insights and optimized/personalized my treatments.
Sorry for the long winded response- I always seem to do that
- but this is another example of how we can take control of our treatments for this terrible disease.
All my best to you and my fellow myeloma patients in their journey.
Dan in Phoenix
Thanks for the very interesting and informative feedback from the lab and for providing their actual answers. The ASCO abstract is most convincing because without these kinds of studies the results are purely academic. They don't break out their multiple myeloma patients but as you note they only analyzed two.
Their responses seem reasonable since they do a short term culture only. I know from professional experience that there are often excess cells left over from diagnostic biopsies- especially relapse or active disease. As a patient I know first hand how difficult BM biopsies can be- I truly hate them- and the pain they can cause.
I was working in a cutting edge molecular pathology lab at Georgetown's Lombardi CC after my diagnosis and actually set up a ~1500 specimen tumor bank from EXCESS tissue. Mostly BM but also blood, lymph nodes ect. The bank actually benefited the patients because as new tests came on-board we could thaw their original samples and test them to see if they originally had certain markers or gene expression.
This was before HIPPA and the rules were more relaxed. Many of our patients were kids with leukemia. In the 1980s and we were just on the cusp of curing most patients. I treated their specimens as "solid gold"- hoping that this was going to be the only chance to capture their diseased cells because chances were good they would be treated, not relapse and be cured of their disease.
Every patient (or parent) signed an agreement that their tissues could be used for research. Today patients have to consent for specific studies so my tumor bank would need to be de-identified to be useful. I think this is fair so patients know exactly what is done with their tissue.
I think this is one reason why patients who go to the top meyeloma centers with active research programs can often get the best treatments and result. Their excess specimens can be used for research instead of simply being thrown away.
AGAIN, DIAGNOSIS IS THE FIRST PRIORITY, ONLY AGREE TO PROVIDE TISSUE THAT IS EXCESS-NOT NEEDED. I don't know about you but the idea of wasting a million or more of my cells is not efficient and doesn't help anyone.
JK- for me this thread has opened up an interesting issue for multiple myeloma patients. As active participants in our care we should ask our doctors what research can be done with any excess diagnostic tissue from our biopsies. The best centers have their own studies but patients like you can also select their own uses for excess tissues. I know that I have had tissue sent to a specialty genetics lab and been very pleased that I did- it provided me and my doctors with important insights and optimized/personalized my treatments.
Sorry for the long winded response- I always seem to do that
- but this is another example of how we can take control of our treatments for this terrible disease.All my best to you and my fellow myeloma patients in their journey.
Dan in Phoenix
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Dan in Phoenix
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