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Biotech / Medical : Incyte (INCY) -- Ignore unavailable to you. Want to Upgrade?

To: Biotech Jim who wrote (2859)	5/9/2013 10:37:07 PM
From: Biomaven	Respond to of 3202

Perhaps relevant: Int J Oncol. 2013 Apr 25. doi: 10.3892/ijo.2013.1922. [Epub ahead of print] Silencing of indoleamine 2,3-dioxygenase enhances dendritic cell immunogenicity and antitumour immunity in cancer patients. Sioud M, Sæbøe-Larssen S, Hetland TE, Kærn J, Mobergslien A, Kvalheim G. SourceDepartment of Immunology, Oslo University Radium Hospital, Montebello, N-0310 Oslo, Norway. Abstract Dendritic cells (DCs) are being explored as a therapeutic vaccine for cancers. However, their immunogenic potential is limited by the presence of immunosuppressive factors. Among these factors is the tryptophan-degrading enzyme indoleamine 2,3-dioxygenase (IDO). In this study, we have investigated the safety, immunogenicity and clinical response of IDO-silenced DC vaccine in four patients with gynecological cancers. DCs were transfected with IDO small interfering RNA and mRNA encoding human telomerase reverse transcriptase (hTERT) or survivin, two universal tumour antigens. Silencing of IDO in DCs did not affect the expression of the co-stimulatory molecules CD80 and CD86, but enhanced the expression of the CCR7 and CD40 molecules. IDO-silenced DCs showed superior potency to activate allogeneic T cells compared to their IDO-positive counterparts. The immunisation with this novel DC cancer vaccine was well tolerated and all patients developed delayed-type hypersensitivity skin reaction and specific T-cell response against hTERT and survivin tumour antigens. Perhaps most importantly, the immune response seen in the patients was related to objective clinical response. Thus, IDO silencing can enhance the immunogenic function of DCs in vitro and in vivo. Overall, the data provide proof-of-principle that immunisation with IDO-silenced DC vaccine is safe and effective in inducing antitumour immunity.

To: Biotech Jim who wrote (2859)	5/15/2013 8:27:31 PM
From: scaram(o)uche	Read Replies (1) \| Respond to of 3202

Jim....... Something big happened. The mucin 1 vaccine that Biomira launched seems to work. So we have a pathology-related antigen (self antigen, sort of) for a huge market (NSCLC) that desperately needs a paired ido inhibitor. :-) More in the next post, but, if you liked that last off-topic tease, perhaps you'll love this one.... J Gen Virol. 2013 Apr 11. [Epub ahead of print] Inhibition of indoleamine 2, 3- dioxygenase (IDO) enhances the T cell response to influenza virus infection. Fox JM, Sage LK, Huang L, Barber J, Klonowski KD, Mellor AL, Tompkins M, Tripp RA. University of Georgia Influenza infection induces an increase in the level of indoleamine 2, 3-dioxygenase (IDO) activity in the lung parenchyma. IDO is the first and rate limiting step in the kynurenine pathway where tryptophan is reduced to kynurenine and other metabolites. The depletion of tryptophan, and production of associated metabolites, attenuates the immune response to infection. The impact of IDO on the primary immune response to influenza virus infection was determined using the IDO inhibitor 1-methyl-D, L-tryptophan (1MT). C57BL/6 mice treated with 1MT and infected with A/HKx31 influenza virus had increased numbers of activated and functional CD4+, influenza-specific CD8+ T cells, and effector memory cells in the lung. Inhibition of IDO increased the Th1 response in CD4+ T cells as well as enhanced the Th17 response. These studies show that inhibition of IDO engenders a more robust T cell response to influenza virus, and suggests an approach for enhancing the immune response to influenza vaccination by facilitating increased influenza-specific T cell response.

To: Biotech Jim who wrote (2859)	5/15/2013 8:51:20 PM
From: scaram(o)uche	Respond to of 3202

I just reread your message and realized that a response that I've been drafting for two days is irrelevant. I thought you were asking which cancers might be resolved by targeted T cells. >> how many oncologic situations represent T cell mediated disease wherein IDO could be downstream and thus a compelling target? << I don't have a clue. My focus has been on the global change that ido inhibition has on the potential for a given response, T axis, B axis, whatever. I hadn't thought of ido inhibition in terms of targeting a given malignancy, and I don't remember seeing anything like that crossing in my screens. I'll watch for stuff. Rick

To: Biotech Jim who wrote (2859)	7/24/2013 2:14:54 PM
From: scaram(o)uche	Respond to of 3202

as 1-methyl-DL- tryptophan is likely a micromolar inhibitor, and the INCY compound is a nanomolar inhibitor You'll enjoy this..... ncbi.nlm.nih.gov