Pharmaceutical compositions containing extracted MHC molecules, for stimulation of the immune system
Allo-, iso- and xenoantigens, chosen from histocompatibility molecules obtained by extraction from homogenates of tissues or cells with Nonidet P40 or 1 N HClO 4 , are disclosed for use as a medicament for stimulation of the immune system of man and mammals, and in particular for cancer therapy.
1 - 16 . (canceled)
17 . A kit useful for the treatment of a carcinoma in a patient, comprising at least two containers, each comprising an extract from an animal tissue, serum or cell source wherein said extracts
a) comprise allogeneic or xenogeneic MHC molecules;
b) are prepared by a) homogenizing the tissue, serum or cell source in the presence of NP40, or b) treating said source with an acid, or c) treating said source with a proteolytic enzyme; and
c) are each effective to reduce the number of tumor cells in the patient compared to the number of tumor cells if the patient is not so treated,
wherein the source of the extract in one container is from i) a tissue, serum or cell different from the tissue, serum or cell for the other container, and from the same animal; ii) a tissue, serum or cell from a different animal of the same species as the animal source for the other container; or iii) a tissue, serum or cell from an animal from a different species as the animal source for the other container.
18 . The kit of claim 17 , wherein the extracts in each container originate from a different species.
19 . The kit of claim 17 , wherein said animal is a human.
20 . The kit of claim 17 , wherein said tissue, serum or cell source is goat, calf or pig liver, or bovine red blood cells.
21 . The kit of claim 17 , wherein said MHC molecules have a molecular weight above 10,000 daltons and are extracted from the tissue, serum or cell source with one or more detergents.
22 . A method for the preparation of the kit of claim 17 , comprising preparing the extracts from at least two different animal tissue, serum of cell sources.
23 . The method of claim 22 , in which the extracts in each container are extracted from different species.
24 . The method of claim 22 , further comprising homogenizing said tissues, sera or cells in the presence of Nonidet P40, centrifuging the homogenate and separating the supernatant, and dialyzing the supernatant against PBS through membranes with a cutoff of at least 10 kDa.
25 . The method of claim 24 , wherein said homogenization is carried out until cell lysis is substantially complete, and wherein 150 to 450 ml of PBS and 0.3 to 1.8% Nonidet P40 (v/v) are used for each 100 g of original material.
26 . A method for the treatment of a carcinoma comprising administering to a patient at least two doses of extracts from an animal tissue, serum or cell source, wherein each of said extracts
a) comprises allogeneic or xenogeneic MHC molecules;
b) is prepared by a) homogenizing the tissue, serum or cell source in the presence of NP40, or b) treating it with an acid, or c) treating it with a proteolytic enzyme; and
c) is effective to reduce the number of tumor cells in the patient compared to the number of tumor cells if the patient is not so treated and
wherein one of said extracts is extracted from an animal tissue, serum or cell source and the other is extracted from a different such source, wherein each of said doses is in an amount effective to reduce the number of tumor cells in the patient compared to the number of tumor cells if the patient is not so treated.
27 . The method of claim 26 , wherein the at least two extracts originate from different species.
28 . The method of claim 27 , wherein said extracts from different species are administered sequentially or alternately.
29 . The method of claim 26 , wherein said animal is a human.
30 . A kit useful for the treatment of a carcinoma in a patient, comprising at least two containers, each comprising an amount of MHC molecules which may be found in extracts from an animal tissue, serum or cell source, wherein said extracts
a) comprise allogeneic or xenogeneic MHC molecules;
b) are prepared by a) homogenizing the tissue, serum or cell source in the presence of NP40, or b) treating said source with an acid, or c) treating said source with a proteolytic enzyme; and
c) are each effective to reduce the number of tumor cells in the patient compared to the number of tumor cells if the patient is not so treated,
wherein the source of the extract in one container is from i) a tissue, serum or cell different from the tissue, serum or cell for the other container, and from the same animal; ii) a tissue, serum or cell from a different animal of the same species as the animal source for the other container; or iii) a tissue, serum or cell from an animal from a different species as the animal source for the other container.
31 . A kit of claim 17 wherein the molecular weight of said MHC molecules is about 43000, 13000, 33000, 34000 or 29000 daltons.
32 . A kit of claim 17 wherein at least one of said animals is calf.
33 . A method of claim 28 wherein said doses are daily doses and are alternated every week.