TY - JOUR
T1 - Lack of comparability between binding of monoclonal antibodies to melanoma cells in vitro and localization in vivo
AU - Mccready, David R.
AU - Balch, Charles M.
AU - Fidler, Isaiah J.
AU - Murray, James L.
N1 - Funding Information:
Received August 29, 1988; revised December 6, 1988; accepted February 10, 1989. Supported in part by Public Health Service grant CA-42107 (to I. J. Fidler) and core grant CA-16672 from the National Cancer Institute, National Institutes of Health, Department of Health and Human Services. D. R. McCready and C. M. Balch (Department of General Surgery, Division of Surgery), I. J. Fidler (Department of Cell Biology), and J. L. Murray (Department of Clinical Immunology and Biological Therapy), The University of Texas M. D. Anderson Cancer Center, Houston, TX. We thank Ms. Lisa Daniels, Mr. Mike Moore, Mr. Mammon John, and Dr. Janet Price for technical assistance. We also thank Dr. Michael linger, Hybritech, Inc., for supplying the antibodies and " 'Indium. *Correspondenceto:JamesL.Murray,M.D.,U.T.M.D.Anderson Cancer Center, Box 41, 1515 Holcombe Blvd., Houston, TX 77030.
PY - 1989/5/3
Y1 - 1989/5/3
N2 - The affinity and specificity of monoclonal antibodies (MAbs) to tumor-associated antigens are often determined by in vitro assays. The specific binding of two anti-human melanoma antibodies (96.5 and ZME-018) and a control antibody (ZCE-025) to three human melanoma cell lines (DX3, A375-M, and Hs294t) was examined under in vitro conditions and compared to in vivo localization of 111In-labeled antibodies to the same cells growing as solid tumors in the subcutis of nude mice. The in vitro binding of the specific MAbs to the tumor cells did not predict in vivo localization. Under in vitro conditions, MAb ZME-018 bound to all three cell lines at levels exceeding that of 96.5, yet ZME-018 did not show superior localization to subcutaneous tumors. MAb 96.5 bound to cultured DX3 cells at levels exceeding those observed with A375-M cells. Yet, 96.5 localized better to A375-M xenografts in nude mice than to DX3 or Hs294t xenografts. Antigen expression differed between in vitro and in vivo growing cells, as evidenced by alteration in binding of 96.5 to tumor cells dissociated from solid subcutaneous tumors. Collectively, the data suggest that in vitro parameters do not predict the clinically relevant localization of MAbs to tumors. [J Natl Cancer Inst 81: 682-687, 1989]
AB - The affinity and specificity of monoclonal antibodies (MAbs) to tumor-associated antigens are often determined by in vitro assays. The specific binding of two anti-human melanoma antibodies (96.5 and ZME-018) and a control antibody (ZCE-025) to three human melanoma cell lines (DX3, A375-M, and Hs294t) was examined under in vitro conditions and compared to in vivo localization of 111In-labeled antibodies to the same cells growing as solid tumors in the subcutis of nude mice. The in vitro binding of the specific MAbs to the tumor cells did not predict in vivo localization. Under in vitro conditions, MAb ZME-018 bound to all three cell lines at levels exceeding that of 96.5, yet ZME-018 did not show superior localization to subcutaneous tumors. MAb 96.5 bound to cultured DX3 cells at levels exceeding those observed with A375-M cells. Yet, 96.5 localized better to A375-M xenografts in nude mice than to DX3 or Hs294t xenografts. Antigen expression differed between in vitro and in vivo growing cells, as evidenced by alteration in binding of 96.5 to tumor cells dissociated from solid subcutaneous tumors. Collectively, the data suggest that in vitro parameters do not predict the clinically relevant localization of MAbs to tumors. [J Natl Cancer Inst 81: 682-687, 1989]
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U2 - 10.1093/jnci/81.9.682
DO - 10.1093/jnci/81.9.682
M3 - Article
C2 - 2709424
AN - SCOPUS:0024505811
SN - 0027-8874
VL - 81
SP - 682
EP - 687
JO - Journal of the National Cancer Institute
JF - Journal of the National Cancer Institute
IS - 9
ER -