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Re: bioshortsqueezer post# 4431

Wednesday, 07/04/2007 11:27:13 PM

Wednesday, July 04, 2007 11:27:13 PM

Post# of 12660
>>> That is, the explanation is that no such response is necessary; the infusion of GM-CSF-stimulated DCs is enough to stimulate the appropriate T cells. <<<


Exactly , almost. "the infusion of GM-CSF fusion protein -stimulated DCs is enough to stimulate the appropriate T cells"

Provenge = Anyvenge. The GM/CSF-PAP fusion protein is a unique non-self antigen and would be expected to elicit an immune response in a manner similar to other foreign proteins ---like KLH , maybe ? ( That's my guess anyway , in the absence of data suggesting a better explanation for the Provenge MOA. )

See :

http://tinyurl.com/2ma97o

Cancer Immunol Immunother. 2007 Jun;56(6):897-903.

Antigen-independent immune responses after dendritic cell vaccination.

Leonhartsberger N, Ramoner R, Putz T, Gander H, Rahm A, Falkensammer C, Bartsch G, Thurnher M.
Department of Urology, Innsbruck Medical University, 6020 Innsbruck, Austria.

The ability of cultured, antigen-loaded dendritic cells (DCs) to induce antigen-specific T cell immunity in vivo has previously been demonstrated and confirmed. Immune monitoring naturally focuses on immunity against vaccine antigens and may thus ignore other effects of DC vaccination. Here we therefore focused on antigen-independent responses induced by DC vaccination of renal cell carcinoma patients. In addition to the anticipated response against the vaccine antigen KLH, vaccination with CD83(+) monocyte-derived DCs resulted in a strong increase in the ex vivo proliferative and cytokine responses of PBMCs stimulated with LPS or BCG. In addition, LPS strongly enhanced the KLH-induced proliferative and cytokine response of PBMCs. Moreover, proliferative and cytokine responses of PBMCs stimulated with the homeostatic cytokines IL-7 and IL-15 were also clearly enhanced after DC vaccination. In contrast to LPS induced proliferation, which is well known to depend on monocytes, IL-7 induced proliferation was substantially enhanced after monocyte depletion indicating that monocytes limit IL-7 induced lymphocyte expansion. Our data indicate that DC vaccination leads to an increase in the ex vivo responsiveness of patient PBMCs consistent with a DC vaccination induced enhancement of T cell memory. Our findings also suggest that incorporation of bacterial components and homeostatic cytokines into immunotherapy protocols may be useful in order to enhance the efficacy of DC vaccination and that monocytes may limit DC vaccination induced immunity.

PMID: 17106716 [PubMed - indexed for MEDLINE]

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