Dentritic cells? What?

One Mexican clinic says this ---"The procedure involves drawing from the patient bloodcontaining mature and immature DC's and tumor cells. A bio-chemistinduces the maturation and activation of DC's in the presence ofproteins derived from the patient's tumor."( see http://www.citylightsnews.com/ce/ibc-vaccines-22dec03.htm )Now, knowing how extremely difficult it is to even detect circulatingcancer cells, and the extraordinary sophistication of the techniquesinvolved I am very doubtful that this quack clinic is producing anauthentic vaccine. Normally a biopsy sample of the patient's tumour isneeded.Any thoughts?

My reply:

This article seems to be several months (at least) old:

http://www.skincancer.org/melanoma/dentritic.php
"...Automated leukapheresis and countercurrent centrifugal elutriation can isolate a lymphocyte fraction and a comobined monocyte/iDC fraction, which represents nearly complete capture of these cells from the circulation. Because calcium mobilization induces both monocytes and iDC to acquire activated DC characteristics, the combined monocyte/iDC fraction requires only overnight CI treatment to convert its entire cellular contents to activated DC."


Tumor vaccines were all the rage in research several years ago, some subsequent research (clinical trials) were dissappointing, some remain uncompleted and/or unpublished. Still no vaccine has FDA approval. But there are open clinical trials (phase III) and some very optimistic proponents.

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what the devil is "elutriation"? Is it something like eluting?Can centrifuging a white cell fraction really separate out thelymphocytes from the monocytes? Must be a hell of a fine centrifuge.Biochemists please post

my reply:

My knowledge base here is limited to clinical outcomes of the human studies with tumor vaccines, I had not put much thought into how hard it may be to acquire or otherwise generate enough dendritic cells to even conduct a treatment. A reference in something I had on hand led me here:

Wong EC, Maher VE, Hines K, Lee J, Carter CS, Goletz T, Kopp W, Mackall CL, Berzofsky J, Read EJ. Development of a clinical-scale method for generation of dendritic cells from PBMC for use in cancer immunotherapy. Cytotherapy. 2001;3(1):19-29. MID: 12028840 (available on MEDLINE)

Since this didn't look like the exact same method as outlined in the article, I put my own search terms in MEDLINE using "dendritic" and "immunotherapy." There are well over 60 references to scientific publications just in 2004. (Maybe this is still hotter than I led myself on to think.) On casual perusal, I didn't get the impression that obtaining/generating at least suitable autologous dendritic cells involves any kind of onerous undertaking. It did, however, leave me even more skeptical of whatever real or pretended protocol they could be following at any cross-border cancer clinic.

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Doesn't imiquimod induce a Th1 response at the site of application? Which would raise the question of timing. And the nature of vaccine in general.

My reply:

I am far from an oncology researcher, but since I was familiar with some of the existing clinical outcomes research on tumor vaccines, I new I could quickly find a reputable reference to indicate that preparing dendritic cells for treatment is feasibly done, and could be a part of a cross-border cancer treatment. Skincancer.org is a #1 public info cite for skin cancer.
Anyway, confessing my ignorance, I did just a cordial search and can agree you may be right:

Movassagh M, Spatz A, Davoust J, Lebecque S, Romero P, Pittet M, Rimoldi D, Lienard D, Gugerli O, Ferradini L, Robert C, Avril MF, Zitvogel L, Angevin E. Selective accumulation of mature DC-Lamp+ dendritic cells in tumor sites is associated with efficient T-cell-mediated antitumor response and control of metastatic dissemination in melanoma. Cancer Res. 2004 Mar 15;64(6):2192-8. PMID: 15026362

I read a few more abstracts and found this fascinating. One study came up with a way to generate DC-tumor cell hybrids through electrofusion that may be better at generating a primary T-cell response. Of course, it seems since they use allo dendritic cells rather than auto, they can more easily create a market.

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My specific concern is that I was sure a sample of cancer tissue wasneeded to produce an authentic vaccine. Did you find anything aboutthis in your searches?

my reply:
That's the idea. You have to have a tumor antigen which, in almost all cases tried so far, comes from tumor tissue itself. Then, like a vaccine, you do something to it so it becomes ineffective except in provoking an autoimmune antibody response. Autologous dendritic cells are great because you can pulse them with peptides, RNA or DNA material, or other tumor tissue cell properties to provoke the autoimmune/antibody response rather than using chunks of the inactivated tumor cells themselves.

The impression I got was that using dendritic cells in formulating a tumor vaccine is something rather new and innovative. Research seems much more further along (Phase III, for the most part) using vaccines made from whole (allogeneic) dead or lysed tumor cells. There's at least one study using autologous tumor cells for a vaccine, and one using peptides or proteins from tumor cells.

I'm sure there's better, more accurate information available on-line than what I'm coming up with here. For now, I suggest that the theory is sound for dendritic cell derived tumor vaccines, but since May 2004 published research has barely arrived at a basis for the development of a protocol for application, anything a cross-border clinic has to offer on this would probably appear very dubious. Interferon is available for melanoma now, and there are other pretty predictable treatments, and treatment is NOT something you want to fool around with here.