Abstract
Background: CC49 is a monoclonal antibody directed against a pancarcinoma antigen (TAG-72) expressed by colorectal cancers. The use of murine CC49 in radioimmunoguided surgery (RIGS) was problematic because of the human anti-mouse antibodies (HAMA) generated. This study was designed to assess the clearance, safety, and effectiveness of localization of a complimentarity determining region (CDR)-grafted humanized domain-deleted antitumor CC49 antibody (HuCC49°CH2).
Methods: After thyroid blockade, 1 mg of HuCC49°CH2 radiolabeled with 2 mCi of iodine-125 was administered. All patients subsequently underwent traditional exploration followed by a survey with the gamma-detecting probe. In five patients, exploration was performed 10 to 24 days after injection, when precordial counts were sufficiently low (<30 counts per 2 seconds [cp2s]). Traditionally suggestive and probe-positive tissue was biopsied or excised and examined for the presence of carcinoma, when considered appropriate by the operating surgeon. Serum was assessed for HAMA.
Results: Seventeen sites were identified as suggestive of carcinoma on traditional exploration and 21 by RIGS. Of these, pathologic correlation was obtained in 15. The sensitivity of RIGS was 92%, and the positive predictive value was 100%. None of the patients expressed significant HAMA.
Conclusions: This initial study indicates that the HuCC49°CH2 monoclonal antibody, when used with RIGS, is safe and sensitive in detecting recurrent intra-abdominal colon cancer.
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Epenettos AA, Kosmas C. Monoclonal antibodies for imaging and therapy. Br J Cancer 1989;59:152–155.
Halpern SE, Abdel-Nabi H, Murray L. Radioimmunoimaging. Quo vadis? Toward the imaging of tumor. J Nucl Med 1990;31:1436–1443.
Epenetos AA, Snook D, Durbin H, Johnson PM, Taylor-Papadimitriou J. Limitations of radiolabeled monoclonal antibodies for localization of human neoplasms. Cancer Res 1986;46:3183–3191.
Courtenay-Luck NS, Epenetos AA, Moore R, et al. Development of primary and secondary immune responses to mouse monoclonal antibodies used in the diagnosis and therapy of malignant neoplasms. Cancer Res 1986;46:6489–6494.
Schroff RW, Foon KA, Beatty SM, Oldham RK, Morgan AC. Human anti-murine immunoglobulin responses in patients receiving monoclonal antibody therapy. Cancer Res 1995;45:879–885.
Boulianne GL, Hozumi N, Shulman M. Production of functional chimaeric mouse/human antibody. Nature 1984;312:643–646.
Hird V, Verheyen M, Badley RA, et al. Tumour localization with a radioactively labeled reshaped human monoclonal antibody. Br J Cancer 1991;64:911–914.
Boven E, Haisma JH, Bril H, et al. Tumour localization with 131-I labelled human IgM monoclonal antibody 16.88 in advanced colorectal cancer patients. Eur J Cancer 1991;27:1430–1436.
Buchsbaum DJ, Hanna DE, Randall BC. Radiolabelling of monoclonal antibody against carcinoembryonic antigen with 88Y and biodistribution studies. Int J Nucl Med Biol 1985;12:79–82.
Martin EW Jr., Thurston MO. The use of monoclonal antibodies (MAbs) and the development of an intraoperative hand-held probe for cancer detection. Cancer Invest 1996;14:560–571.
Kalofonos HP, Sivolapenko GB, Courtenay-Luck NS, et al. Antibody guided targeting of non-small cell lung cancer using 111In-labeled HMFG1 F(ab′)2 fragments. Cancer Res 1988;48:1977–1984.
Huston JS, Levinson D, Mudgett-Hunter M, et al. Protein engineering of antibody binding sites: recovery of specific activity in an anti-digoxin single-chain Fv analogue produced in Escherichia coli. Proc Natl Acad Sci U S A 1988;85:5879–5883.
Swallow DM, Gendler S, Griffiths B, et al. The human tumour-associated epithelial mucins are codes by an expressed hypervariable gene locus PUM. Nature 1987;328:82–84.
Sivolapenko GB, Douli V, Epenetos AA, et al. Breast cancer imaging with radiolabeled peptide from complementarity-determining region of antitumour antibody. Lancet 1995;346:1662–1666.
Bakalakos EA, Young DC, Martin EW Jr. Radioimmunoguided surgery for the patients with liver metastases secondary to colorectal carcinoma. Ann Surg Oncol 1998;5:590–594.
Schneebaum S, Troitsa A, Haddad R, et al. Immunoguided lymph node dissection in colorectal cancer: a new challenge?. World J Surg 2001;25:1495–1498.
Arnold MW, Hitchcock CL, Young DC, Burak WE, Bertsch DJ, Martin EW Jr. Intra-abdominal patterns of disease dissemination in colorectal cancer identified using radioimmunoguided surgery. Dis Colon Rectum 1996;39:509–513.
Khazaeli MB. Quantitation of mouse monoclonal antibody and human anti-mouse antibody response in serum of patients. Hybridoma 1989;8:231–239.
Forero A, Meredith RF, Khazaeli MB, et al. A novel monoclonal antibody design for radioimmunotherapy. Cancer Biother Radiopharm 2003;18:751–759.
Hine KR, Dykes PW. Prospective randomized trial of early cytotoxic therapy for recurrent colorectal carcinoma detected by serum CEA. Gut 1984;25:682–688.
Ahn JH, Kim TW, Lee JH, et al. Oral doxifluridine plus leucovorin in metastatic colorectal cancer: randomized phase II trial with intravenous 5-fluorouracil plus leucovorin. Am J Clin Oncol 2003;26:98–102.
Fuchs CS, Moore MR, Harker G, Villa L, Rinaldi D, Hecht JR. Phase III comparison of two irinotecan dosing regimens in second-line therapy of metastatic colorectal cancer. J Clin Oncol 2003;21:807–814.
Kabbinavar F, Hurwitz HI, Fehrenbacher L, et al. Phase II, randomized trial comparing bevacizumab plus fluorouracil (FU)/leucovorin (LV) with FU/LV alone in patients with metastatic colorectal cancer. J Clin Oncol 2003;21:60–65.
Drebin JA, Niederhuber JE. Cancer of the lower gastrointestinal tract. In: Niederhauber JE, ed. Current Therapy in Oncology. St. Louis: Mosby-Year Book, Inc., 1992:426–31.
Cohen AM, Martin EW Jr., Lavery I, et al. Radioimmunoguided surgery using iodine 125 B72.3 in patients with colorectal cancer. Arch Surg 1991;126:349–352.
Goel A, Baranowska-Kortylewicz J, Hinrichs SH, et al. 99mTc-labeled divalent and tetravalent CC49 single-chain Fv’s: novel imaging agents for rapid in vivo localization of human colon carcinoma. J Nucl Med 2001;42:1519–1527.
Martin DT, Hinkle GH, Tuttle S, et al. Intraoperative radioimmunodetection of colorectal tumor with a hand-held radiation detector. Am J Surg 1985;150:672–675.
Slavin-Chiorini DC, Kashmiri SV, Lee HS, et al. A CDR-grafted (humanized) domain-deleted antitumor antibody. Cancer Biother Radiopharm 1997;12:305–316.
Kashmiri SV, Iwahashi M, Tamura M, Padlan EA, Milenic DE, Schlom J. Development of a minimally immunogenic variant of humanized anti-carcinoma monoclonal antibody CC49. Crit Rev Oncol Hematol 2001;38:3–16.
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Agnese, D.M., Abdessalam, S.F., Burak, W.E. et al. Pilot Study Using a Humanized CC49 Monoclonal Antibody (HuCC49°CH2) to Localize Recurrent Colorectal Carcinoma. Ann Surg Oncol 11, 197–202 (2004). https://doi.org/10.1245/ASO.2004.05.010
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DOI: https://doi.org/10.1245/ASO.2004.05.010