Immunomodulatory Protocol

[Itchygo]

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Can someone explain to me what an immunomodulatory protocol is in a way that a normal person can understand please? I've done research, but there is no way a person like me can understand all the information.

 

[Goro]

Do you mean immunosuppression?

 

[The Knife & Gun Club]

If it's the same as an immunosuppressive protocol, it would be the cocktail and dosing scheme of various immunosuppressive drugs given (usually to transplant patients, although sometimes for severe autoimmune conditions too) to suppress a persons natural immune response. It's like a collection of drugs with dosings that change over time, and the whole protocol has been studied and shown to have certain outcomes. From the research I've done in the field, an immunosuppressive protocol usually includes things like steroids and calcinurin inhibitors (spelling?). Disclaimer though that I'm not a physician, just someone who does transplant research

 

[Itchygo]

If it's the same as an immunosuppressive protocol, it would be the cocktail and dosing scheme of various immunosuppressive drugs given (usually to transplant patients, although sometimes for severe autoimmune conditions too) to suppress a persons natural immune response. It's like a collection of drugs with dosings that change over time, and the whole protocol has been studied and shown to have certain outcomes. From the research I've done in the field, an immunosuppressive protocol usually includes things like steroids and calcinurin inhibitors (spelling?). Disclaimer though that I'm not a physician, just someone who does transplant research

Surgeons and researchers working on VCA research at Johns Hopkins are using an immunomodulatory / minimization protocol for immunosuppression after transplant. It is composed of two elements: Treating the patient with antibodies on the day of transplant, followed by a donor bone marrow infusion several days later. When used in solid organ and composite tissue transplants, this protocol allows patients to be treated with low doses of a single maintenance drug after being transplanted.

That's what it means. I don't understand it.

 

[The Knife & Gun Club]

confused what you're asking lol, but this is what my lab does research in too (albeit in monkeys not people)

 

[deleted503015]

What's your question?

From my (extremely brief) transplant rotation, it is my understanding that right now, multiple drugs or high dose drugs are needed immediately after organ transplantation for induction of immunosuppression, which is then tapered to reach a lower, long-term maintenance level. High levels of immunosuppression are dangerous, so it sounds like the trial you describe above is trying to reduce the intial amount of immunosuppression needed. Intraoperative antibodies are, I think, already used in some transplants (Campath?) but the bone marrow thing would be new. Wonder how they make the patients tolerate the marrow though.

There are pretty decent uptodate articles on induction and maintenance immunosuppression in transplant patients.

 

[The Knife & Gun Club]

Yea they usually start out with a super potent hit (or a few) of a drug called thymo (anti-thymocyteglobulin I think) that basically wipes out your ability to mount an acute immune response. Then they start you on CNIs, steroids, maybe co-stimulation blockade drugs, and some stuff in order to prevent the body from mounting an immune response.

The theory behind the marrow, at least in our lab, is that it has natural immunomodulatory properties in the human body and so it can suppress chronic rejection in the long term. This way you can take fewer drugs, many of which have nasty side effects like renal failure, and have the same outcome.

If you don't mind me asking, what journal did that quote came from?

There's a couple different ways to give marrow with a transplant. The one I'm most familiar with is to give weekly infusions of cultured mesichimal stromal cells (MSCs, may have botched the spelling there), but it sounds like they're describing something else like a whole marrow infusion into the actual bone...

 

[ZX10R]

Surgeons and researchers working on VCA research at Johns Hopkins are using an immunomodulatory / minimization protocol for immunosuppression after transplant. It is composed of two elements: Treating the patient with antibodies on the day of transplant, followed by a donor bone marrow infusion several days later. When used in solid organ and composite tissue transplants, this protocol allows patients to be treated with low doses of a single maintenance drug after being transplanted.

That's what it means. I don't understand it.

Transplant cells have different MHC's then donors. You cannot not prevent ischemia in a transplant therefor macrophages will be called to dispose of ischemic cells and process what they are disposing. If you have a T-cell/B-cell pair that identifies donor MHC due to antigen processing, the donor tissue will be targeted and destroyed. Prior to surgery Recipient is given Anit-G4 (more complicated than this but I'm dumbing it down) Abs shutting down a possible cascade of B-cell/T-cell proliferation/Pro inflammatory response.

Recpeints of the past had to be put on hardcore immuno-suppressants that weakened the immune system and really only saved the organ for at most 10-15 years (Under perfect MHC matches). The recipient will eventually form an immune response against the donor tissue because sadly, no organ is immune to ill-regular necrosis AKA a cell gets unlucky and T-cell/macrophages respond. What your quote is proposing is putting donor hemopoeitic cells/stem cells in recipients bone marrow after abating it. The goal therefore; is as B-cells are maturing they will go under negative selection for donor MHCs. Now remember this is only b-cells, as immature T-cells go under selection in the thymus until involution. If all goes as planned B-cells will not be made against donor tissue so the amount of immuno-suppressant drugs are less. BEWARE: This is a very simplistic explanation of what is going on.