These findings suggest that L86-8275 is a candidate for further preclinical development, as well as a model for the synthesis of other flavonoids that might potently delay cell cycle progression to achieve inhibition of tumor growth. Future studies need to address optimal schedules for antiproliferative activity in vivo and inhibition of clonogenic activity.

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Three murine monoclonal antibodies (MAbs) reactive to different epitopes on CEA were selected according to their ability to bind to various human tissue sections. The most selective MAb, BW 431/31, bound to the majority of colon carcinomas but only faintly to normal colon mucosa. In addition to the tissues stained by MAb BW 431/31, MAb BW 250/183 reacted with granulocytes, colon mucosa and faintly with pancreatic ducts. The third MAb, BW 374/14, reacted with granulocytes, colon mucosa, strongly with pancreatic ducts and with alveolar and bronchial epithelium. The antigenic determinants recognized by the 3 MAbs in human tissue sections were resistant to formaldehyde fixation and paraffin embedding as well as to periodic acid oxidation and neuraminidase treatment. The last two treatments suggest that the epitopes are protein in nature. Using MAb affinity chromatography, 3 antigen preparations were isolated from a human colon carcinoma xenograft with an approximate molecular weight of 180 kd. These preparations were shown to bear the epitopes from each of the MAbs and from a polyclonal antiserum specific for purified CEA. Furthermore, the ability of MAb BW 431/31 to localize its antigenic determinant in vivo on a human colon carcinoma xenograft is evaluated and its possible application in the patient is suggested.

A major problem of tumor gene therapy is the low transduction efficiency of the currently available vectors. One way to circumvent this problem is the delivery of therapeutic genes encoding intracellular enzymes for the conversion of a prodrug to a cytotoxic drug which can then spread to neighboring non-transduced cells (bystander effect). One possibility to improve the bystander effect could be the extracellular conversion of a hydrophilic prodrug to a lipophilic, cell-permeable cytotoxic drug. Toward this end, we have used a secreted form of the normally lysosomal human ␤-glucuronidase (s-␤Gluc) to establish an extracellular cytotoxic effector

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