Susan S. Leong

Potential Therapeutic Effect of Adriamycin-Monoclonal Anti-prostatic Acid Phosphatase Antibody Conjugate on Human Prostate Tumor

Adriamycin was conjugated to an IgG1 monoclonal antibody specific for human prostatic acid phosphatase via a dextran bridge. The adriamycin-monoclonal antibody conjugate retained substantially the original immunological activity of the antibody. Antitumor effect of the conjugate in vitro was studied by its inhibition on RNA synthesis in human prostate tumor cells (LNCaP), which exhibited a higher inhibition than that by an identically prepared adriamycin-normal mouse IgG conjugate but was less than that by free adriamycin. The loss in pharmacological activity of the conjugate in vitro was proportional to the extent of dextran oxidation. Antitumor effect in vivo demonstrated that adriamycin-monoclonal antibody conjugate greatly inhibited the growth of xenografted prostate tumor, as compared with control groups, only in the early phase of experiment. These results suggested that although adriamycin conjugated to monoclonal anti-PAP antibody via a dextran bridge may be a potential reagent for experimental immunochemotherapy of prostate tumor, caution must be exercised at this stage of development.

Purified human fibroblast interferon in vivo: skin reactions and effect on bone marrow precursor cells.

Human interferon from normal diploid fibroblasts, purified by sequential chromatography on concanavalin A-agarose and phenyl-sepharose, was administered parenterally in 4 subjects. Fever, marked skin hypersensitivity reactions and suppression of marrow stem cells (estimated by the count of myeloid colony-forming cells), side-effects common for less purified fibroblast and leukocyte interferons, were absent. Purified fibroblast interferon retained antiviral and immunomodulatory activity, evidenced by reduction of the blastogenic response of peripheral lymphocytes and decrease of hepatitis B virus markers in a patient with chronic hepatitis B infection treated with this substance.

Differential Susceptibility of Spleen Focus-Forming Virus and Murine Leukemia Viruses to Ansamycin Antibiotics

The streptovaricin complex (SvCx) and rifamycin SV derivatives display potent antiviral activity against the polycythemic strain of Friend leukemia virus (FV-P), as measured by a reduction in the number of spleen foci produced in mice. Such reductions may be explained by inactivation of functions of (i) the spleen focus-forming virus (SFFV), (ii) its “helper” murine leukemia virus (MuLV), or (iii) both viruses normally present in FV-P. We noted that preincubation of FV-P with fractionation products of SvCx, or derivatives of rifamycin SV, at low concentrations (3 to 5 μg/ml) reduces the number of spleen foci 80 to 97%, whereas titers of MuLV (from the same inoculum) remain unaffected (MuLV titers were measured by XC, S+L−, and “helper activity” assays). Our findings indicate a remarkable biological selectivity of ansamycins, as well as nonansamycin components of SvCx, against the transforming and defective spleen focus-forming virus as compared to MuLV. Thus, the drugs might be useful in distinguishing other types of oncornaviruses.

Activity of Pure Streptovaricins and Fractionated Streptovaricin Complex Against Friend Virus

Chromatographic fractionation of streptovaricin complex yields two stable components enriched (4- to 16-fold) in activity directed against the polycythemic strain of Friend virus; both components apparently contain no streptovaricins. When compared with their unfractionated parent streptovaricin complex, eight individual intact streptovaricins (A through G and J) show at least a 30-fold reduction in antiviral activity. These results further support the conclusion that the diversified biological properties of streptovaricin complex probably reside in different molecular structures.

Antivirion Effects of Streptovaricin Complex Against Friend Virus

The in vitro antivirion activities of five different streptovaricin complex lots against the polycythemic strain of the Friend virus were evaluated. The assay system was based on the inhibition of the Friend virus-induced spleen foci. The virus inactivation process was shown to be susceptible to variation in temperature, pH, and time. The antivirion activity and the acute toxicity for mice, as well as the optical properties of these streptovaricin complexes, do not co-vary; this suggests that their biological activities are not associated with a single molecular structure. In addition, the antivirion activity of the five preparations of streptovaricin complex differs about 30-fold, indicating that this activity does not reside in a major component of the complex.