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The potent capacity of B6 anti-AD755a tumor cell serum to protect mice against challenge with large doses of the homologous tumor cells has been shown to reside in the IgG2a antibody subclass. Despite their inability to protect in vivo, other IgG subclass antibodies obtained from the anti-AD755a serum demonstrated serologic reactivities in vitro comparable to those obtained with the protective IgG2a fraction. The specificity of serum protection is linked to the oncornavirus associated with the AD755a tumor and the serum immunoprecipitates only virus structural proteins from the tumor cell surface. Removal of these antibodies by specific immunoadsorbent resins eliminated nearly all of the in vitro serologic reactivity of unfractionated serum and the IgG2a subclass, but it had absolutely no effect on their protective capacity in vivo. Further target cell-binding studies suggest that nonprotective antibodies in the anti-AD755a serum bind more efficiently to the target cell in vitro than the protective fraction and have raised the possibility that the latter antibodies may only have weak affinity for the target cell itself.

An in vitro assay has been developed that mimics the potent in vivo protective capacity of B6 anti-AD755a serum in a passive therapy protocol. In the presence of small volumes of hyperimmune serum or IgG2a antibody, thioglycollate-elicited B6 mouse peritoneal cells (PEC) inhibit the growth of AD755 Cl.10 target cells and other cells provided that they express FLV-related antigens. When hyperimmune serum is replaced by normal serum, or elicited PEC from BALB/c mice are used, growth inhibition of the AD755 Cl.10 target cells is not seen. The latter is in accord with the inability to protect BALB/c mice with the anti-AD755a serum. Tumor cells to which antibody has been pre-bound are not inhibited by thioglycollate-elicited B6 PEC, analogous to the undiminished tumorigenicity of antibody-bound AD755a cells in vivo. These results, along with those presented in the accompanying papers, have led to the construction of a model to explain the specificity and mechanism of the potent in vivo passive protection characteristic of this system. The major features of this model are that the protective IgG2a antibody must first interact with an appropriate host effector cell, presumably of the monocyte/macrophage lineage, and that such an antibody-directed cell then binds to the tumor cell and effects its elimination, possibly by a phagocytic mechanism.

We have previously described a passive serum therapy system in which potent protection against challenge of syngeneic mice with large doses (10(4) X LD100) of AD755a tumor cells can be accomplished by administration of as little as 2 to 5 microliters/mouse of hyperimmune anti-tumor cell serum. The present results demonstrate that the efficacy of the serum protection effect is strain-dependent and is under the control of a single genetic locus, denoted ADP-1. Through a series of crosses between highly protected C57BL/6J and nonprotected BALB/cJ mice, the ADP-locus has been mapped to chromosome 2 [linkage group V], approximately 23 centimorgans toward te centromere from the locus controlling agouti coat color. Thus, the protection locus is not linked to either the H-2 region or to previously described loci regulating the replication and disease induction of type-C viruses closely related to the virus associated with the AD775a tumor. The possible functions of the ADP-1 locus are discussed and further aspects of this experimental model are described in the accompanying papers.