Abstract
Immunohistology provides a necessary but insufficient criterion for selecting monoclonal antibodies (MAbs) capable of tumour targeting in vivo. Additional selection procedures have been evaluated using a panel of anti-melanoma MAbs, including immunoreactivity of (labelled) MAbs, antibody affinity, kinetics of binding and release, apparent antigen density and accumulation in nude mouse transplants. According to these criteria, MAbs M.2.7.6 and M.2.9.4 showed the most favourable properties, i.e. high immunoreactivity and pronounced internalization into melanoma cells. With MAbs M.2.10.15 and KG 6–56, moderate immunoreactivity and a binding pattern characterized by temperature dependence in the absence of internalization was observed. According to the paired label assay, all four MAbs showed specific accumulation into solid melanoma tissue. However, application in the patient still requires evaluation of the side effects of antigen cross-expression on normal human tissues.
Keywords: Melanoma, Nude Mouse, Melanoma Cell, Selection Procedure, Tumour Target
References
- 1.Bradwell AR, Fairweather DS, Dykes PW, Keeling A, Vaughan A, Taylor J. Limiting factors in the localization of tumours with radiolabelled antibodies. Immunol Today. 1985;6:163. doi: 10.1016/0167-5699(85)90146-X. [DOI] [PubMed] [Google Scholar]
- 2.Bröcker E-B, Suter L, Brüggen J, Ruiter DJ, Macher E, Sorg C. Phenotypic dynamics of tumor progression in human malignant melanoma. Int J Cancer. 1985;36:29. doi: 10.1002/ijc.2910360106. [DOI] [PubMed] [Google Scholar]
- 3.Brüggen J, Sorg C. Detection of phenotypic differences on human malignant melanoma lines and their variant sublines with monoclonal antibodies. Cancer Immunol Immunother. 1983;15:200. doi: 10.1007/BF00199165. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Brüggen J, Bröcker E-B, Suter L, Redmann K, Sorg C. The expression of tumor-associated antigens in primary and metastatic human malignant melanoma. Behring Inst Mitt. 1984;64:19. [PubMed] [Google Scholar]
- 5.Capone PM, Papsidero LD, Chu TM. Relationship between antigen density and immunotherapeutic response elicited by monoclonal antibodies against solid tumors. J Natl Cancer Inst. 1984;72:6733. [PubMed] [Google Scholar]
- 6.Ey PL, Prowse SJ, Jenkin CR. Isolation of pure IgG1, IgG2a, and IgG2b immunoglobulins from mouse serum using protein A-sepharose. Immunochemistry. 1978;15:429. doi: 10.1016/0161-5890(78)90070-6. [DOI] [PubMed] [Google Scholar]
- 7.Fidler IJ. General considerations for studies of experimental cancer metastasis. Methods Cancer Res. 1978;15:399. [Google Scholar]
- 8.Fraker PJ, Speck JC. Protein and cell membrane iodinations with a sparingly soluble chloroamide, 1, 3, 4, 6-tetrachloro-3a, 6a-diphenylglycoluril. Biochem Biophys Res Commun. 1980;80:849. doi: 10.1016/0006-291x(78)91322-0. [DOI] [PubMed] [Google Scholar]
- 9.Houghton AN, Eisinger M, Albino AP, Cairncross JG, Old LJ. Surface antigens of melanocytes and melanomas. Markers of melanocyte differentiation and melanoma subsets. J Exp Med. 1982;156:1755. doi: 10.1084/jem.156.6.1755. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10.Kennel SJ, Foote LJ, Lankford PK, Johnson M, Mitchell T, Braslawsky GR. Direct binding of radioiodinated monoclonal antibody to tumor cells: significance of antiboy purity and affinity for drug targeting or tumor imaging. Hybridoma. 1983;2:297. doi: 10.1089/hyb.1983.2.297. [DOI] [PubMed] [Google Scholar]
- 11.Lindmo T, Boven E, Cuttitta F, Fedorko J, Bunn PA. Determination of the immunoreactive fraction of radiolabeled monoclonal antibodies by linear extrapolation to binding at infinite antigen excess. J Immunol Methods. 1984;72:77. doi: 10.1016/0022-1759(84)90435-6. [DOI] [PubMed] [Google Scholar]
- 12.Matzku S, Kirchgeßner H, Dippold W, Brüggen W. Immunoreactivity of monoclonal anti-melanoma antibodies in relation to the amount of radioactive iodine substituted to the antibody molecule. Eur J Nucl Med. 1985;11:260. doi: 10.1007/BF00279081. [DOI] [PubMed] [Google Scholar]
- 13.Matzku S, Bröcker E-B, Brüggen J, Dippold WG, Tilgen W. Modes of binding and internalization of monoclonal antibodies to human melanoma cells. Cancer Res. 1986;46:3848. [PubMed] [Google Scholar]
- 14.Pressman D, Day ED, Blau M. The use of paired labeling in the determination of tumor-localizing antibodies. Cancer Res. 1975;17:845. [PubMed] [Google Scholar]
- 15.Suter L, Bröcker E-B, Brüggen J, Ruiter DJ, Sorg C. Heterogeneity of primary and metastatic human malignant melanoma as detected with monoclonal antibodies in cryostat sections of biopsies. Cancer Immunol Immunother. 1983;16:53. doi: 10.1007/BF00199906. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 16.Trucco M, de Petris S. Determination of equilibrium binding parameters of monoclonal antibodies specific for cell surface antigens. In: Lefkovits I, Pernis B, editors. Immunological methods vol II. New York: Academic Press; 1981. p. 1. [Google Scholar]
- 17.Wilson BS, Imai K, Natali PG, Ferrone S. Distribution and molecular characterization of a cell-surface and a cytoplasmic antigen detectable in human melanoma cells with monoclonal antibodies. Int J Cancer. 1981;28:293. doi: 10.1002/ijc.2910280307. [DOI] [PubMed] [Google Scholar]