Methods for promoting dendritic cell proliferation or differentiation
OwnerGere S. diZerega, Kathleen E. Rodgersinventors
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Abstract
The present invention provides methods, pharmaceutical compositions, and kits for promoting dendritic cell proliferation and differentiation, through the use one or more of renin, angiotensinogen, angiotensinogen converting enzyme (ACE), neutral endopeptidase, angiotensin I (AI), AI analogues, AI fragments and analogues thereof, angiotensin II (AII), AII analogues, AII fragments or analogues thereof or AII AT2 type 2 receptor agonists, angiotensin converting enzyme inhibitors (ACE inhibitors). Such methods are useful, for example, for promoting tumor vaccine production, or for improving the efficacy of a tumor vaccine.
Claims19
A method for promoting dendritic cell proliferation or differentiation comprising contacting the dendritic cells with an amount effective to promote dendritic cell proliferation or differentiation of at least one active agent comprising a sequence of at least three contiguous amino acids of groups R1-R8 in the sequence of general formula I
- R1-R2-R3-R4-R5-R6-R7-R8
- wherein R1 s selected from the group consisting of H, Asp, Glu, Asn, Acpc (1-aminocyclopentane carboxylic acid), Ala, Me2Gly, Pro, Bet, Glu(NH2), Gly, Asp(NH2) and Suc,
- RB is selected from the group consisting of Arg, Lys, Ala, Om, Ser(Ac), Sar, D-Arg and D-Lys;
- R3 is selected from the group consisting of Val, Ala, Leu, Lys, norLeu, Ile, Gly, Pro, Aib, Acpc and Tyr;
- R4 is selected from the group consisting of Tyr, Tyr(PO3)2, Thr, Ser, Ala, homoSer and azaTyr;
- R5 is selected from the group consisting of Ile, Ala, Leu, norLeu, Val and Gly;
- R6 is selected from the group consisting of His, Arg or 6-NH2-Phe;
- R7 is selected from the group consisting of Pro or Ala;
- and
- R8 is selected from the group consisting of phe, phe(br), ile and tyr, excluding sequences including r4 as a terminal tyr group:
A pharmaceutical composition comprising:
- (a) an amount effective to promote dendritic cell proliferation of an active agent consisting essentially of a sequence selected from the group consisting of SEQ ID NO:
- 1, SEQ ID NO:4 or SEQ ID NO:9;
- (b) an amount effective to promote dendritic cell proliferation or tumor vaccine production cytokine selected from the group consisting of GM-CSF, M-CSF, TNF-c, IL-1, I1-2, IL-4, IL-6, IL-12, Flt3-L, interferons, immunoglobulin superfamily molecules, chemokines;
- and
- (c) a pharmaceutically acceptable carrier.
Dependencies are inferred from the claim text.