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Protective Effect of Immune Sera against Transplantable Moloney Virus-induced Sarcoma and Lymphoma

Viral Biology Branch, National Cancer Institute, NIH, Bethesda, Maryland 20014

Sera from mice immunized with Moloney sarcoma virus (MSV)-induced antigens were quantitated for antibodies by indirect membrane immunofluorescence (MF), cytotoxicity, and neutralization. These sera were then tested in vivo to determine whether antibody titers measured by these three methods would correlate with the effectiveness of the serum in preventing the growth of a transplantable Moloney virus-induced sarcoma (MSC) or lymphoma (LSTRA). The sources of sera were (a) BALB/c mice with progressively growing MSV-induced tumors (progressor serum); (b) BALB/c mice in which MSV-induced tumors regressed (regressor serum); and (c) BALB/c ¢ DBA F₁ mice immunized with multiple inoculations of MSV-induced allogeneic tumor cells (C57BL origin; allogeneic serum). The pooled progressor sera showed low antibody titers in all three tests. In contrast, the pooled regressor and allogeneic sera were positive in the MF and neutralization tests, although neither showed any cytotoxic activity. The MF and neutralization titers with the allogeneic serum were 2 to 4 times higher than with the regressor serum. Pretreatment of recipient mice with regressor or allogeneic sera as early as 3 days before challenge with MSC tumors resulted in (respectively) 60 and 84% survivors free of disease when the experiments were terminated at 75 days. In contrast, resistance was not noted following pretreatment with the progressor sera. The allogeneic serum was also effective against the rapidly growing transplantable Moloney leukemia virus-induced lymphoma designated LSTRA. Single injections of this serum in mice either 3 or 1 day before LSTRA challenge or 2 days after challenge resulted in significant numbers of survivors during the period of observation. Multiple injections of this serum during the latent period for tumor development resulted in up to 90% survivors, free of apparent disease, when the experiments were terminated at 60 days. These results demonstrated that the effectiveness of a serum in these systems in preventing tumor growth correlated closely with its MF and neutralization titers and suggested that measurement of antibody titers by conventional methods, particularly MF, might provide useful information on the potential therapeutic value of serum in the control of cancer.

Received 7/28/72. Accepted 10/12/72.

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