Mouse monoclonal antibody (mAb) BCD-F9, which recognizes an unknown antigen found on the surface of many tumor cells, was used to screen a phage display library expressing random peptide decamers. The phage that was selected encoded the unique sequence GRRPGGWWMR, representing the peptide capable of binding to the BCD-F9 mAb. The peptide was synthesized and found to specifically inhibit the binding of mAb to HT-1080 fibrosarcoma cells. Alanine mutagenesis of the sequence encoding this peptide indicated that three residues, PXXWW, were critical for its binding to the BCD-F9 mAb. Polyclonal antibodies generated by immunization of rabbits with the synthetic peptide GRRPGGWWMR (anti-mimotope antiserum or AM-F9) bound specifically to HT-1080 cells and inhibited the binding of the BCD-F9 mAb to these cells. Using an experimental animal model in which CD-1 nude mice are inoculated i.v. with HT-1080 cells, develop lung metastasis, and die within 30 days, we have shown that AM-F9 could significantly prolong the life span of these animals. Our results suggest that a peptide mimotope can potentially be used as a novel immunotherapy to induce a beneficial antitumor response.

01 Jun 1994·Nuclear Medicine CommunicationsQ4 · MEDICINE

implication for the detection limit of immunolymphoscintigraphy in the assessment of axillary lymph node metastases

Q4 · MEDICINE

Article

Author: Czerwenka, K ; Kubista, E ; Schatten, C ; Angelberger, P ; Barrada, M ; Pateisky, N ; Enzelsberger, H ; Mandeville, R

To determine whether the detection limit of immunolymphoscintigraphy (ILS), reported to be > or = 1 cm, can be improved by comparing imaging after administration of breast cancer-specific monoclonal antibody (MAb) BCD-F9 and breast cancer-nonspecific 4C4, 25 patients with suspected breast cancer were given injections of both 123I-labelled MAbs. The ILS was performed independently for both MAbs, the 4C4 scans serving as an ipsilateral negative control, and was used preoperatively to detect lymph node metastases. Twenty-one patients had breast cancer of whom 11 patients suffered from axillary involvement. Single interpretation of BCD-F9 scans gave true positive results in six of 11 and true negative results in 12 of 14 patients, whereas combined interpretation of BCD-F9 and 4C4 scans gave true positive results in nine of 11 and true negative results in 14 of 14 patients. On the basis of comparison of scintigrams of both MAbs, ILS allowed the detection of lymph node metastases 0.3-0.8 cm in diameter (n = 3). Immunohistochemistry of BCD-F9 and 4C4 MAbs of tumour-free and tumour-bearing lymph nodes correlated with ILS, with the exception of one patient. The study suggests that comparing scans obtained with BCD-F9 and 4C4 MAbs may improve the detection limit of ILS in the preoperative staging of axillae.

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Indication	Highest Phase	Country/Location	Organization	Date
Neoplasms	Preclinical	CA	Supratek Pharma, Inc.	-
Neoplasms	Preclinical	CA	University of Quebec	-
Neoplasms	Preclinical	CA	Biophage Pharma, Inc.	-

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