Reduced tumorigenicity of threshold syngeneic tumor inocula in xid-bearing mice treated with natural antibodies.

Several correlative experimental approaches have provided evidence that polyclonal serum natural antibodies (NAb) participate in the defense against small syngeneic tumor foci in vivo. The threshold subcutaneous tumor inoculum model of incipient neoplasia has consistently revealed an inverse relationship between tumorigenicity in vivo and the NAb binding capacity of the tumor injected or the anti-tumor NAb levels of the recipient animals, including B cell-deficient mice bearing the xid mutation of the CBA/N mouse strain. Now passive i.v. administration of whole normal syngeneic serum NAb in bolus injections, given I each day beginning on day -2, -1 or 0 prior to the threshold s.c. challenge of xid-bearing CBA/N or male (CBA/N x CBA/J)F1 mice with syngeneic RI-28 lymphoma cells, consistently and significantly reduced their tumorigenicity assayed as tumor appearance and latency. Three similar injections of an ammonium sulfate-precipitated fraction of whole serum NAb also reduced tumor frequency and latency, while a combination of purified IgG and IgM NAb reduced the appearance of tumors slightly and increased the survival of recipients. The reconstitution of the xid-defect in anti-tumor NAb provides more direct evidence to substantiate a role for NAb in the defense against early tumor development in vivo and establishes a model for the dissection of the in vivo mechanisms of the NAb anti-tumor activity.