caa a22 4500 46907390X CHVBK 20180323132929.0 cr unu---uuuuu 170328e19920701xx s 000 0 eng 10.1007/BF01789331 doi (NATIONALLICENCE)springer-10.1007/BF01789331 Tissue localization of methotrexate-monoclonal-IgM immunoconjugates: Anti-SSEA-1 and MOPC 104E in mouse teratocarcinomas and normal tissues [Elektronische Daten] [Byron Ballou, Ronald Jaffe, Stefano Persiani, Wei-Chiang Shen, John Langone, Howard Sands, Jean Reilandu, Joseph Curley, Thomas Hakala] Summary: Methotrexate (MTX) was coupled to the tumor-targeting monoclonal IgM, anti-SSEA-1 and the nontargeting myeloma IgM, MOPC 104E. At 24-h intervals following injection, drug deposition in MH-15 teratocarcinomas and in several normal tissues was followed by immunoperoxidase microscopy using the M16 monoclonal antibody to MTX. MTX-anti-SSEA-1 was deposited on the surface and in the interior of living tumor cells 24 h after injection; at 48 h and after, only low-level binding to necrotic tissue was found. There was no significant gradation in staining from the outside to the interior of the tumors. In tumors, the control MOPC 104E immunoconjugate was detectable only in necrotic tissue. Binding to SSEA-1-expressing normal tissues was undetectable, except for pericryptal fibroblasts in the small intestine. No significant pathology was found in normal tissues that are SSEA-1 positive. High levels of the immunoconjugate were detected in the liver, where MTX was found predominantly in Kupffer cells and possibly in hepatocytes; again, no significant morphological changes were associated with this retention. Thus tumor-associated antigens can be suitable targets for antibody-drug conjugates even when present in normal tissues and in large quantities, provided that the antigens in normal tissues are inaccessible. Moreover, deposition in viable tumor tissue can be assessed using monoclonal antibodies to methotrexate. Springer-Verlag, 1992 Immunotoxins nationallicence Methotrexate nationallicence Immunoenzyme techniques nationallicence Antibodies, monoclonal nationallicence Ballou Byron Division of Urological Surgery, University of Pittsburgh, 15261, Pittsburgh, PA, USA aut Jaffe Ronald Department of Pathology, Children's Hospital, 15213, Pittsburgh, PA, USA aut Persiani Stefano Division of Urological Surgery, University of Pittsburgh, 15261, Pittsburgh, PA, USA aut Shen Wei-Chiang School of Pharmacy, University of Southern California, 90033, Los Angeles, CA, USA aut Langone John Department of Medicine, Baylor College of Medicine, 77030, Houston, TX, USA aut Sands Howard Dupont Merck, Experimental Station, 19880-0328, Wilmington, DE, USA aut Reilandu Jean VAMC, University Drive C, 15240, Pittsburgh, PA, USA aut Curley Joseph Department of Pathology, Children's Hospital, 15213, Pittsburgh, PA, USA aut Hakala Thomas Division of Urological Surgery, University of Pittsburgh, 15261, Pittsburgh, PA, USA aut Cancer Immunology, Immunotherapy Springer-Verlag 35/4(1992-07-01), 251-256 0340-7004 35:4<251 1992 35 262 https://doi.org/10.1007/BF01789331 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/BF01789331 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Ballou Byron Division of Urological Surgery, University of Pittsburgh, 15261, Pittsburgh, PA, USA aut NATIONALLICENCE 700 1- Jaffe Ronald Department of Pathology, Children's Hospital, 15213, Pittsburgh, PA, USA aut NATIONALLICENCE 700 1- Persiani Stefano Division of Urological Surgery, University of Pittsburgh, 15261, Pittsburgh, PA, USA aut NATIONALLICENCE 700 1- Shen Wei-Chiang School of Pharmacy, University of Southern California, 90033, Los Angeles, CA, USA aut NATIONALLICENCE 700 1- Langone John Department of Medicine, Baylor College of Medicine, 77030, Houston, TX, USA aut NATIONALLICENCE 700 1- Sands Howard Dupont Merck, Experimental Station, 19880-0328, Wilmington, DE, USA aut NATIONALLICENCE 700 1- Reilandu Jean VAMC, University Drive C, 15240, Pittsburgh, PA, USA aut NATIONALLICENCE 700 1- Curley Joseph Department of Pathology, Children's Hospital, 15213, Pittsburgh, PA, USA aut NATIONALLICENCE 700 1- Hakala Thomas Division of Urological Surgery, University of Pittsburgh, 15261, Pittsburgh, PA, USA aut NATIONALLICENCE 773 0- Cancer Immunology, Immunotherapy Springer-Verlag 35/4(1992-07-01), 251-256 0340-7004 35:4<251 1992 35 262 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer