Methods and compositions for detecting human tumors
AssigneeThe Regents of the University of California
InventorsMartin J. Cline, Dennis J. Slamon
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Abstract
Methods and compositions for detecting the presence of tumors are provided, where a physiological sample is assayed for the expression product of a c-onc gene as diagnostic for the presence of the tumor. The method finds use in both pre- and postoperative situations with a host suspected of having transformed malignant cells.
Claims22
A method for evaluating the probability of cellular malignancy in a human host, said method comprising:
- bringing into close association (1) a probe specific for a cellular product, said cellular product being mRNA or its expression product, where said mRNA is complementary to a DNA sequence of a retrovirus capable of transforming a normal cell to malignancy and said probe is a nucleic acid sequence capable of duplexing with said mRNA or antibody capable of binding to said expression product, and (2) a source from said human host suspected of containing cellular product;
- and
- determining the level of binding of said probe to said cellular product, wherein an elevated level is indicative of the presence of cellular malignancy.
A method for evaluating the probability of leukemia in a human host, said method comprising:
- combining antibodies specific for the oncogene myb and blood cells from a human host suspected of having leukemia;
- and
- determining the level of binding of said antibodies to said host blood cells as diagnostic of a leukemic host.
A method for substantially eliminating human malignant cells from a combination of human malignant and normal cells, which comprises:
- combining under cytotoxic conditions said combination of cells with an antibody specific for an expression product of a DNA sequence present in a retrovirus genome or substantially complementary to said DNA sequence, which sequence is expressed in said malignant cells as a surface protein;
- and
- isolating normal cells, substantially free of malignant cells.
A method for treating a human host suspected of having malignant cells, which comprises:
- administering to said human host under cytotoxic conditions antibodies to the expression product of a gene, which gene is part of a retrovirus genome capable of inducing malignancy in a normal cell or which gene is substantially complementary to said gene of said retrovirus genome.
Antibodies specific for the expression product of the human oncogenes c-myc, c-fos, c-ras.sup.Ha, c-ras.sup.Ki, c-fes, c-myb, and c-src.
An antigenic oligopeptide selected from the class consisting of:
- (a) met-ala-phe-ala-his-asn-pro-pro-ala-gly-pro-leu-pro-gly-ala
- (b) pro-phe-his-lys-asp-gln-thr-phe-thr-glu-tyr-arg-lsy-met-his-gly-gly-ala-va
- (c) pro-phe-his-lys-asp-gln-thr-phe-thr-glu-tyr-arg-lys-met
- (d) asp-asn-thr-arg-thr-ser-gly-asp-asn-ala-pro-val-ser-cys-leu-gly-glu
- (e) arg-leu-ileu-glu-asp-asn-glu-tyr-thr-ala-arg-gln-gly-ala-lys-phe-pro
- (f) trp-arg-arg-asp-pro-glu-glu-arg-pro-thr
- (g) arg-leu-lys-lys-ileu-ser-lys-glu-glu-lys-thr-pro-gly-cys-val-lys-ileu-lys- lys
- (h) asp-leu-pro-ser-arg-thr-val-asp-thr-lys-gln-ala-gln-glu-leu-ala-arg
- (i) met-thr-glu-tyr-lys-leu-val-val-val-gly-ala-ser-gly-val-gly-lys-ser-ala
- (j) glu-asp-ileu-his-gln-try-arg-glu-gln-ileu-lys-arg-val-lys-asp-ser-asp-asp
- (k) val-arg-glu-ileu-arg-gln-his-lys-leu-arg-lys-leu-asn-pro-pro-asp-glu-ser-g ly-pro
- (l) met-thr-glu-tyr-lys-leu-val-val-val-gly-ala-gly-gly-val-gly-lys-ser-ala
- (m) val-asp-glu-tyr-asp-pro-thr-ileu-glu-asp-ser-tyr-arg-lys-gln-val
- (n) arg-his-ser-thr-ser-ser-ser-glu-gln-glu-arg-glu-gly-gly-arg
- (o) asn-gln-gln-thr-arg-glu-phe-val-glu-lys-gly-gly-arg
- (p) pro-glu-val-gln-lys-pro-leu-his-glu-gln
- (q) ala-ser-pro-tyr-pro-asn-leu-ser-asn-gln-gln-thr-arg
- (r) arg-leu-ileu-ala-glu-lys-glu-gln-leu-arg-arg-arg-arg-glu-gln
- (s) asn-asn-glu-lys-ala-pro-lys-val-val.
Antibodies raised to an antigenic polypeptide selected from the class consisting of:
- (a) met-ala-phe-ala-his-asn-pro-pro-ala-gly-pro-leu-pro-gly-ala;
- (b) pro-phe-his-lys-asp-gln-thr-phe-thr-glu-tyr-arg-lys-met-his-gly-gly-ala-va l;
- (c) pro-phe-his-lys-asp-gln-thr-phe-thr-glu-tyr-arg-lys-met;
- (d) asp-asn-thr-arg-thr-ser-gly-asp-asn-ala-pro-val-ser-cys-leu-gly-glu;
- (e) arg-leu-ileu-glu-asp-asn-glu-tyr-thr-ala-arg-gln-gly-ala-lys-phe-pro;
- (f) trp-arg-arg-asp-pro-glu-glu-arg-pro-thr;
- (g) arg-leu-lys-lys-ileu-ser-lys-glu-glu-lys-thr-pro-gly-cys-val-lys-ileu-lys- lys;
- (h) asp-leu-pro-ser-arg-thr-val-asp-thr-lys-gln-ala-gln-glu-leu-ala-arg;
- (i) met-thr-glu-tyr-lys-leu-val-val-val-gly-ala-ser-gly-val-gly-lys-ser-ala;
- (j) glu-asp-ileu-his-gln-tyr-arg-glu-gln-ileu-lys-arg-val-lys-asp-ser-asp-asp;
- (k) val-arg-glu-ileu-arg-gln-his-lys-leu-arg-lys-leu-asn-pro-pro-asp-glu-ser-g ly-pro;
- (l) met-thr-glu-tyr-lys-leu-val-val-val-gly-ala-gly-gly-val-gly-lys-ser-ala;
- (m) val-asp-glu-tyr-asp-pro-thr-ileu-glu-asp-ser-tyr-arg-lys-gln-val;
- (n) arg-his-ser-thr-ser-ser-ser-glu-gln-glu-arg-glu-gly-gly-arg;
- (o) asn-gln-gln-thr-arg-glu-phe-val-glu-lys-gly-gly-arg;
- (p) pro-glu-val-gln-lys-pro-leu-his-glu-gln;
- (q) ala-ser-pro-tyr-pro-asn-leu-ser-asn-gln-gln-thr-arg;
- (r) arg-leu-ileu-ala-glu-lys-glu-gln-leu-arg-arg-arg-arg-glu-gln;
- and
- (s) asn-asn-glu-lys-ala-pro-lys-val-val.
Dependencies are inferred from the claim text.