Drug – bio-affecting and body treating compositions – Immunoglobulin – antiserum – antibody – or antibody fragment,... – Binds expression product or fragment thereof of...
Patent
1994-11-07
1998-06-09
Feisee, Lila
Drug, bio-affecting and body treating compositions
Immunoglobulin, antiserum, antibody, or antibody fragment,...
Binds expression product or fragment thereof of...
4241981, 4241451, 4241581, 4241741, 530399, 53038824, A61K 3818, A61K 3900, A61K 39395, C07K 1600
Patent
active
057629315
DESCRIPTION:
BRIEF SUMMARY
BACKGROUND OF THE INVENTION
Human chorionic gonadotropin (hCG) is normally made by the trophoblast as an early hormonal signal of pregnancy. Its inactivation by bio-effective antibodies leads to the prevention of pregnancy. One of us, Talwar, has been involved in the development of two types of birth control vaccines, which induce the formation of antibodies competent to inactivate the bioactivity of hCG and thus control fertility. We have now found an additional use of such vaccines and the antibodies generated by them in prevention and cure of cancers secreting hCG. hCG and/or its .alpha. or .beta. subunits are observed to be made by a number of cancers as ectopic products. Our recent studies on one is such cancer, e.g. the human lung cancer, demonstrate that hCG and/or its subunits made by the human lung cancer cells act as autocrine growth promoters for the tumour cells. Furthermore, antibodies inactivating the hormone or its subunits arrest the growth of tumour cells in soft agar as also on progression of implanted tumour in nude mice in vivo. In cases in which antibodies are given to the animal prior to the implantation of the human lung cancer, the tumour fails to grow. The effect is dose dependent. When the antibodies are given to nude mice in which the tumour has previously grown, the antibodies cause necrosis of the tumour. These examples demonstrate the utility of the antibodies and/or the vaccines generating such antibodies, to cure as well as prevent hCG secreting tumours.
The birth control vaccine may, for example, be a vaccine of the type disclosed in U.S. Pat. No. 4,780,312 issued 25 Oct. 1988 (inventor: G. P. Talwar). Another type of birth-control vaccine with this utility as an anti-cancer agent is a recombinant birth-control vaccine of the type disclosed in WO 91/05049 (inventors: G. P. Talwar et al).
Rivera et al in J. Cell Biol. 108: 2423-2434 (1989) showed that a clonal strain of human lung tumour cells which secrete large amounts of alpha and lower levels of beta subunits of human chorionic gonadotropin (hCG) in culture lose characteristics associated with tumorigenic potential (anchorage-independent growth) when in the presence of anti-alpha-hCG antibody. This effect could be partially reversed by adding alpha-hCG to the medium.
The work of Rivera et al (op. cit.) shows that there is a need to develop a vaccine which is compatible with the immune system of a tumour-containing animal and indeed induces the immune system of the animal to produce antibodies to the tumour.
Various Ohio State University patents to Stevens (e.g. U.S. Pat. No. 4,767,842) disclose the use of a beta-hCG/tetanus toxoid modified peptide (as described in U.S. Pat. No. 4,161,519 to Talwar) as an anti-cancer agent. In U.S. Pat. No. 4,767,842 examples XXXIV and XXXVI to XXXVIII relate to this utility. Some or all of the same examples are also disclosed in other patents related to U.S. Pat. No. 4,767,842. In all Stevens' examples the animals were immunized before exposure to cancer cells and therefore relate to the use of such antigens in the prevention rather than the cure of cancer. Stevens does not show the use of such an antigen in the cure of an already existing cancer.
Talwar (U.S. Pat. No. 4,780,312) and Talwar et al (WO 91/05049) have worked to present a reproductive hormone to the immune system of a female mammal in such a way that the immune system of the female mammal is stimulated to produce antibodies to the reproductive hormone thereby disrupting conception and providing a means of birth control. In a collaborative work from Dr. Biswas's laboratory and Dr. Talwar's laboratory it has been reported that human lung cancer cells in culture which produce the alpha subunit of hCG induced tumours in female athymic mice. These tumours in athymic mice undergo necrotic degeneration following local or intraperitoneal administration of an alpha specific antibody. The alpha hCG specific antibody did not affect the growth of tumours produced by human tumour cells which do not produce alpha-hCG. It is also demonstr
REFERENCES:
patent: 4161519 (1979-07-01), Talwar
patent: 4767842 (1988-08-01), Stevens
patent: 4780312 (1988-10-01), Talwar
patent: 5006334 (1991-04-01), Stevens
Rivera, et al., Loss of Tumorigenic Potential by Human Lung Tumor Cells in the Presence of Antisense RNA Specific to the Ectopically Synthesized Alpha Subunit of Human Chorionic Gonnadotropin The Journal of Cell Biology, vol. 108 2423-2334 (1989).
Wiktor et al., "Protection from Rabies by a Vaccina Virus Recombinant Containing the Rabies Virus Glycoprotein Gene" Proc. Natl. Acad. Sci. USA 81:7194-7198 (1984).
Biswas Debajit K.
Talwar Gursaran P.
Bansal Geetha P.
Feisee Lila
National Institute of Immunology
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