Identification and Enrichment of Cell Subpopulations
Markers useful for the identification, characterization and, optionally, the enrichment or isolation of tumorigenic cells or cell subpopulations are disclosed.
1 .- 136 . (canceled)
137 . A method of producing an animal model for the analysis of pharmaceutical compounds comprising the step of introducing a tumorigenic cell or cell population purified or enriched for one or more TICAM.
138 . The method of claim 137 wherein said tumorigenic cell or cell population is purified or enriched by contacting the cell or cell population with a binding agent that preferably associates with at least one TICAM.
139 . The method of claim 138 wherein said binding agent comprises a protein.
140 . The method of claim 139 wherein said protein comprises an antibody.
141 . The method of claim 140 wherein said antibody preferably associates with a TICAM selected from the group consisting of CCR10, CD9, CD13, CD15, CD24, CD26, CD29, CD32, CD46, CD49a, CD49b, CD49c, CD49f, CD51, CD54, CD55, CD56, CD58, CD63, CD66a, CD66c, CD66e, CD71, CD73, CD81, CD82, CD91, CD98, CD99, CD102, CD104, CD105, CD108, CD111, CD117, CD118, CD130, CD131, CD133, CD136, CD141, CD146, CD147, CD148, CD151, CD155, CD157, CD164, CD166, CD167a, CD172a, CD177, CD186, CD196, CD221, CD230, CD234, CD244, CD245, CD262, CD265, CD273, CD275, CD295, CD298, CD299, CD317, CD318, CD324, CD340, BMPR-1B, Cadherin-11, c-Met, Claudin-3, DLL-1, DLL-3, Eph-B2, Eph-B4, FOLR1, Frizzled-3, Glut-1, Glut-2, Glypican 5, HLA-A/B/C, HLA-A2, HER3, IL-15R, IL-20Ra, Jagged-2, Integrin-a8, Integrin a9b1, Integrin b5, LAG-3, Leukotriene-B4R, Lox-1, LDL-R, MCSP, Mer, Nectin-4, Notch2, NPC, PD-L2, Plexin-B1, Semaphorin 4B, Somatostatin-R2, TROP-2, ULBP2, Vb9 and VEGFR2.
142 . The method of claim 141 wherein said TICAM is selected from the group consisting of CD46, CD324, CD66c and combinations thereof.
143 . The method of claim 141 wherein said antibody comprises a monoclonal antibody.
144 . The method of claim 143 wherein said monoclonal antibody comprises a reporter molecule.
145 . The method of claim 144 further comprising a sorting step wherein said sorting step is selected from the group consisting of fluorescence activated cell sorting, magnetic-assisted cell sorting, substrate-assisted cell sorting, laser capture microdissection, fluorometry, flow cytometry, mass cytometry and microscopy techniques.
146 . The method of claim 137 wherein said subject comprises an immunocompromised mouse or a humanized mouse.
147 . An animal model produced by the method of claim 137 .
148 . A method a method of generating tumor samples comprising the steps of:
a. providing a tumorigenic cell or enriched tumorigenic cell population comprising one or more TICAM;
b. introducing the tumorigenic cell or enriched tumorigenic cell population into a subject;
c. waiting for the tumorigenic cell or cell population to generate a tumor; and
d. harvesting said tumor.
149 . The method of claim 148 wherein said tumorigenic cell or cell population is purified or enriched by contacting the tumorigenic cell or tumorigenic cell population with a binding agent that preferably associates with at least one TICAM.
150 . The method of claim 149 wherein said binding agent comprises an antibody.
151 . The method of claim 148 wherein said tumorigenic cell or enriched tumorigenic cell population has a marker phenotype comprising CD46 hi CD324 + .
152 . The method of claim 151 wherein said subject comprises an immunocompromised mouse or a humanized mouse.
153 . An animal model for the analysis of pharmaceutical compounds comprising a subject implanted with a tumorigenic cell or cell population purified or enriched for one or more TICAM.
154 . The method of claim 153 , wherein said subject comprises an immunocompromised mouse or a humanized mouse.
155 . The method of claim 153 , wherein said tumor cell population is derived from a solid tumor.
156 . The method of claim 155 wherein said solid tumor is obtained from a subject suffering from a neoplastic disorder selected from the group consisting of adrenal cancer, bladder cancer, cervical cancer, endometrial cancer, kidney cancer, liver cancer, lung cancer, ovarian cancer, colorectal cancer, pancreatic cancer, prostate cancer, breast cancer, head & neck cancer, and skin cancer.