This study was designed to determine whether the ability of interferon-γ
to upregulate the expression of a human tumor antigen improved the therapeutic efficacy of a radionuclide-conjugated monoclonal antibody.
Tumor xenografts of the moderately differentiated human colon tumor cell line HT-29 were grown in athymic mice. Constitutive levels of the human tumor antigen, tumor-associated glycoprotein-72, were measured before and after treatment with interferon-γ.
Antitumor effects of an131
I-labeled antitumor-associated glycoprotein-72 monoclonal antibody, CC49, were determined by measuring changes in tumor volumes in the respective groups of athymic mice.
induced a time-dependent and dose-dependent increase in tumor-associated glycoprotein-72 expression in the HT-29 tumors. Immunohistochemical staining revealed a more homogeneous tumor-associated glycoprotein-72-positive tumor cell population in tumors isolated from mice treated for eight days with interferon-γ,
which accounted for the enhanced tumor localization of131
I-CC49 in mice. That experimental model was used to examine the antitumor effects of combining interferon-γ
I-CC49. Administration of 300 μCi of131
I-CC49 to mice bearing HT-29 tumors induced a transient suppression of tumor growth. Conversely, a long-term, sustained HT-29 tumor growth suppression was achieved in mice given 300 μ
I-CC49 and interferon-γ.
In fact, the cytokine/radioimmunoconjugate combination eradicated any evidence of tumor in approximately 30 percent of the mice.
The ability of interferon-γ
to enhance tumor-associated glycoprotein-72 expression substantially augmented the antitumor effects of the radioimmunoconjugate. Those observations provide additional argument for use of a radioimmunoconjugate in combination with a cytokine to improve tumor diagnosis and therapy.