Drug – bio-affecting and body treating compositions – In vivo diagnosis or in vivo testing – Magnetic imaging agent
Patent
1983-10-24
1986-09-09
Metz, Andrew H.
Drug, bio-affecting and body treating compositions
In vivo diagnosis or in vivo testing
Magnetic imaging agent
424 11, 935107, 128630, A61K 4900, A61K 4902
Patent
active
046108696
DESCRIPTION:
BRIEF SUMMARY
tions where they have not been known to exist.
A radioactive-labelled BRM would selectively irradiate tumor tissue in situ, allowing for levels of radioactivity not suitable if nonselectively directed towards the entire patient. A BRM may also be used as a carrier for chemotherapeutic agents. It would then be possible to concentrate the effect of a chemotherapeutic agent in the tumor tissue and allow use of concentrations of chemotherapeutic agents previously ineffective due to the overall destructive effect on a patient.
Other substances useful when conjugated with a BRM are cellular toxins. Examples of cellular toxins include, but are not limited to, diptheria toxin and ricin. A preferred toxin would be one of sufficient toxicity to cause a fatal reaction in tumor cells in a very small dosage. The invention enables administration of BRM-conjugated toxin to destroy tumor tissue without allowing interaction between the toxin and normal tissues.
The present invention also indentifies the MAb of choice for use as a carrier for a cellular toxin. When the MAb of choice is used as a carrier, the ability of the cellular toxin to permeate the cell membrane is increased.
The invention is also useful in determining the potential relative effectiveness of a variety of BRM when used against a particular tumor tissue. This method aids a physician in determining whether a particular BRM should be used in therapy for a patient. A BRM so identified may be used as a therapeutic agent itself or may be used as a tag or carrier to deliver therapeutic agents to the tumor site. The BRM, such as a MAb, may serve as a carrier for a variety of therapeutic agents, including radioactive materials, chemotherapeutic agents, and cellular toxins.
In this embodiment, the invention may be used to screen a battery of BRM to determine the BRM best suited for use in treatment of a patient's tumor. When used for this purpose, the method of the present invention comprises: (a) implanting pieces of fresh tumor tissue of the same type, surgically-obtained from a patient, under the renal capsules of a plurality of host organisms; (b) administering a different biological response modifier to each host organism; and (c) determining which biological response modifier exhibits the greatest response to or specificity for the tumor tissue.
Additionally, the present invention may be used to predict the clinical usefulness of a BRM to a specific type of tumor. Such a prediction is done in a pre-clinical screening of potential BRM and comprises: (a) surgically obtaining, from a plurality of patients, fresh pieces of tumor tissue of the same type; (b) implanting, under the renal capsule of a plurality of host organisms, pieces of fresh tumor tissue; (c) administering the same biological response modifier to each of the plurality of host organisms; and (d) determining the response rate or number of host organisms exhibiting the greatest response to the biological response modifier or greatest interaction between the biological response modifier and the tumor.
The following examples are designed to elucidate the teachings of the present invention, and in no way limit the scope of the invention. Various other modifications and equivalents of the examples will readily suggest themselves to those of ordinary skill in the art, particularly after the issuance of this patent, without departing from the spirit or scope of the present invention.
EXAMPLE 1
In vivo localization of 111-indium-labelled monoclonal carcinoembryonic antigen (CEA) antibody (C-19, specific activity 0.2-0.3 .mu.Cu/.mu.g) in fresh, surgical explants of human colon tumors was determined. Tumor fragments were implanted under the renal capsules of normal, immunocompetent CDF-1 mice, obtained from Animal Genetics and Production Section of the National Cancer Institute, Bethesda, Md., on day 0, using the method of Bogden, et al., The Nude Mouse in Experimental and Clinical Research Vol. 2 (Fogh, J. and Giovanella, B. C., eds.) New York: Academic Press, Inc., 1982. On day 2, 10 .mu.g of labelled
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The Government has rights in this invention pursuant to Contract No. NO1-CM-07325 awarded by the National Cancer Institute.
Chapman Terryence
EG&G Mason Research Institute
Metz Andrew H.
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