Chemistry: molecular biology and microbiology – Animal cell – per se ; composition thereof; process of... – Animal cell – per se – expressing immunoglobulin – antibody – or...
Patent
1995-07-03
1997-10-14
Feisee, Lila
Chemistry: molecular biology and microbiology
Animal cell, per se ; composition thereof; process of...
Animal cell, per se, expressing immunoglobulin, antibody, or...
5303882, 5303891, 5303911, 5303913, 5303917, C12N 512, C07K 1618
Patent
active
056771819
DESCRIPTION:
BRIEF SUMMARY
FIELD OF THE INVENTION
This invention relates to angiogenesis inhibitory antibodies, and to the use thereof in the inhibition of angiogenesis, particularly angiogenesis associated with the growth of solid tumours, with proliferative retinopathies, and with certain inflammatory diseases.
BACKGROUND TO THE INVENTION
The circulatory system represents an extensive, branching, network of blood vessels which is essential for the supply of oxygen and nutrients to tissues and for the removal of byproducts of metabolism. In adults the development of new blood vessels or "angiogenesis" rarely occurs except during wound healing or as a result of a number of pathological situations termed "angiogenesis-dependent diseases".sup.(1,2). The most important of these is the angiogenesis associated with the growth of solid tumours and with proliferative retinopathies. Angiogenesis may also play an important role in rheumatoid arthritis and psoriasis.
Angiogenesis inhibitors can, therefore, be of considerable value in the treatment of angiogenesis-dependent diseases. For example, in the case of solid tumours, the development of a blood supply is essential for the growth and survival of the tumour. Thus, inhibition of angiogenesis can provide a highly selective means of inducing tumour regression. Similarly, angiogenesis inhibitors may be used to prevent the blindness associated with proliferative diabetic retinopathy, one of the major complications of diabetes.
In work leading to the present invention, monoclonal antibodies (mAbs) have been developed against proliferating/angiogenic human endothelial cells which can be used either to directly inhibit angiogenesis or to target cytotoxic drugs or radioisotope labels to sites of angiogenesis. Since angiogenesis does not occur in adults, except following tissue injury, such mAbs can be remarkably specific. Furthermore, unlike other lines of research which have produced cancer cell-specific mAbs to target cytotoxic drugs to tumours, the present invention is directed to producing mAbs against host antigens. This approach has the major advantage that generation of "resistant" variants of the tumour cannot occur and, in theory, one mAb could be used to treat all solid tumours. An additional advantage is that endothelial cells, by virtue of their vascular location, are very accessible to mAbs in the circulation.
SUMMARY OF THE INVENTION
According to the present invention, there are provided antibodies, including monoclonal antibodies, specific for proliferating/angiogenic human endothelial cells. As used throughout the specification and claims, references to "proliferating" cells include "angiogenic" cells, and references to "non-proliferating" cells include "non-angiogenic" cells.
More particularly, the present invention provides antibodies, including monoclonal antibodies, specific for proliferating/angiogenic human umbilical vein endothelial cells (HUVEC) or human umbilical artery endothelial cells (HUAEC).
This invention also extends to hybridoma cell lines producing the monoclonal antibodies as described above, which may be produced by methods well known to persons skilled in this field.
As previously described, the antibodies in accordance with the invention may be used alone as an anti-angiogenesis agent in the treatment of angiogenesis-dependent disease in a patient.
In another aspect, the present invention provides an antibody-conjugate comprising an antibody specific for proliferating/angiogenic human endothelial cells, having a toxin material or label conjugated thereto.
The toxin material may, for example, be a cytotoxic drug or other cytotoxic material, however other toxin materials well known to persons skilled in this art may also be incorporated in the antibody-conjugate of this aspect of the invention. The label may be a radioisotope. Suitable toxin materials include, by way of example, ricin A chain, diphtheria toxin, Pseudomonas exotoxin A and idarubicin. A suitable radiolabel is technetium-99m. Coupling of various toxins to monoclonal antibodies may be effect
REFERENCES:
Hagemeier, Int. J. Cancer Res. 38:481-488, 1986.
Vitetta, Science 238:1098-1104, 1987.
Goldenberg et al. Ch. 13, in Immunoconjugates 1987 pp. 259-280 Oxford Univ. Press, NY.
Wang, Angigenesis EXS 61:266-271 Apr. 22, 1992.
Harris TIBTECH 11:42-44, 1993.
Feisee Lila
Johnson Nancy A.
The Australian National University
LandOfFree
Angiogenesis inhibitory antibodies does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Angiogenesis inhibitory antibodies, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Angiogenesis inhibitory antibodies will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-1554510