Immunohistochemical phenotyping of human solid tumors with monoclonal antibodies in devising biotherapeutic strategies.
A panel of 14 monoclonal antibodies (MoAbs) (4 raised against breast cancer, 6 against colon cancer and 4 against melanoma) were used to phenotype frozen sections of tumor biopsies obtained from 110 patients, by avidin-biotin-peroxidase complex techniques. We observed heterogeneity of antigen expression among the multiple metastatic lesions of single patients, as well as among tumor lesions from different patients with similar tumor histotypes. A wide range of cross-reactivity of anti-(breast-carcinoma) and anti-(colon-carcinoma) MoAbs with other carcinoma histotypes and limited reactivity with melanoma and sarcoma was detected. Some of our anti-melanoma MoAbs were also found to cross-react with selected carcinomas. Nine of the 14 MoAbs most reactive with carcinomas of diverse histotypes have been identified. A mixture or 'cocktail' of different MoAbs could be selected for each individual patient in order to achieve binding of MoAbs with most, if not 100% of tumor cells. This study illustrates the approach that we have taken to individualize the cocktail of MoAbs for the development of patient-specific therapeutic immunoconjugates.
Liao
S K
SK
Biotherapeutics, Inc., Franklin, TN 37064.
Meranda
C
C
Avner
B P
BP
Romano
T
T
Husseini
S
S
Kimbro
B
B
Oldham
R K
RK
D000328:Adult; D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000937:Antigen-Antibody Reactions; D001360:Avidin; D001710:Biotin; D001943:Breast Neoplasms / Q000145:classification / Q000473:pathology / Q000628:therapy; D002277:Carcinoma / Q000145:classification / Q000473:pathology / Q000628:therapy; D003110:Colonic Neoplasms / Q000145:classification / Q000473:pathology / Q000628:therapy; D003429:Cross Reactions; D006735:Horseradish Peroxidase; D006801:Humans; D007124:Immunoenzyme Techniques; D008545:Melanoma / Q000145:classification / Q000473:pathology / Q000628:therapy; D051379:Mice; D009369:Neoplasms / Q000145:classification* / Q000473:pathology / Q000628:therapy; D010641:Phenotype
D000911:Antibodies, Monoclonal; D001360:Avidin; D001710:Biotin; D006735:Horseradish Peroxidase