Compositions and methods for the use of such compositions in hum

Details Compositions and methods for the use of such compositions in hum Compositions and methods for the use of such compositions in hum

1995-11-13

1999-08-03

Marschel, Ardin H.

Drug, bio-affecting and body treating compositions

Lymphokine

424 852, 424 854, 514 1, 514 2, 530350, A61K 4505, A61K 3821, A01N 6100, C07K 100

Patent

active

059322080

DESCRIPTION:

BRIEF SUMMARY
Interferons (more especially .alpha.-interferon) are secreted by leucocytes. They are therefore classed as cytokines, which are mediators produced principally by the cells of the immune system. In general, cytokines may be regarded as hormones characteristic of the immune system. The possibility of producing cytokines by genetic recombination has opened up the way to more detailed studies of the behaviour of some of these cytokines, especially recombinant interferons in animals. Of the interferons, the one which has been studied the most is .alpha.-interferon (.alpha.-IFN) which is sub-divided into .alpha.-IFN 2a, .alpha.-IFN 2b and .alpha.-IFN 2c.
In particular, the antiviral activity of some murine interferons, and even the potentiation of this activity in mice by some derivatives of N-acetyl-muramyl-L-alanyl-D-isoglutamine (MDP) or homologues thereof, have already been demonstrated. On the other hand, as indicated by F. Dianzani in his article entitled "Interferon Treatments: how to use an Endogenous System as a Therapeutic Agent" in the Journal of Interferon Research, Special Issue, May 1992, Mary Ann Liebert, Inc., Publishers, pp. 109-118, the large number of clinical trials carried out on humans with interferons have been "more than disappointing". Although animal tests seemed to open up wide therapeutic possibilities, their poorly controlled secondary effects have meant that it has hitherto been possible to use them only in a restricted number of therapeutic indications. Thus, it has hitherto been proposed to use .alpha.-IFN 2a only in a reduced number of "niches", as indicated also by "Scrip's Cytokines Report", PJB Publications Ltd. 1993, in respect of the difficulties encountered in the use of interferons in human therapeutics: treatments consist in daily administrations or administration at the rate of three times per week of from 5 to 10 million units for from 3 to 6 months. Positive results are observed in from 30 to 40% of cases; chronic myelogenic leukaemia, the uses envisaged are AIDS, Kaposi's syndrome, multiple myeloma, melanoma and certain types of carcinoma.
The serious nature of these syndromes is such that it has also led to the acceptance of the serious secondary effects accompanying the use of .alpha.-IFN in human therapeutics. 98% of patients thus treated suffer from an influenza syndrome, which is often extremely severe, accompanied by nausea, vomiting, disorders of the central and peripheral nervous system and cardiac disorders. These effects are attributed at least in part to the induction by interferon of pyretic mediators which could be IL-1 and prostaglandins, the production of which would be activated by interferon. Added to this are bouts of tiredness, anorexia and weight loss, which could be linked at least in part with the production of TNF and/or the increased expression of TNF receptors which are also induced by interferons. Any procedure which optimised the beneficial effects of interferons or cytokines that can be used therapeutically while at the same time optimising the production of, or the activity of, cytokines or other undesirable biological mediators, such as IL-1, IL-8 and/or TNF (Tumour Necrosis Factor) would be doomed to certain failure.
Finally, the administration of interferons is often accompanied by severe leucopenia and thrombopenia accompanied by a blockage of the maturation of myeloidal precursors. These phenomena make it necessary to interrupt the interferon-based treatments periodically in order to authorise a regeneration of the blood formula each time.
All these disadvantages have hitherto prevented any exploration of the real possibilities of using interferons in human therapeutics, except for the treatment of the few syndromes mentioned above.
Similar difficulties are encountered with other cytokines, the therapeutic value of which would be undisputed if it were possible to overcome these difficulties. This would apply, for example, to IL-2, IL-3, IL-6, G-CSF, M-CSF, GM-CSF, etc . . . TNF and IL-1, the therapeutic possibilities of which can be e

REFERENCES:
Chemical Abstracts 115:222927q (1991).
Chemical Abstracts 112:229333q (1990).
Chemical Abstracts 112:176682u (1990).
Chemical Abstracts 118:73306u (1993).
Malik et al., Br. J. Cancer, 63, 399-403 (1991).
Wyde et al., J. Bio. Response Modifiers, 9, 98-102 (1990).
Azuma et al., Adv. Exper. Med. & Biology, 319, 253-263 (1992).
Pouillart et al., J. Interferon Research, 11, p. S162 (1991).
Pouillart et al., J. Interferon Research, 11, p. S257 (1991).
Sanceau et al., Immunology, 69, 52-56 (1990).

Affiliated with

Also associated with

Rating

Compositions and methods for the use of such compositions in hum does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Compositions and methods for the use of such compositions in hum, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Compositions and methods for the use of such compositions in hum will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-847383