Protective effect of an interspecies hybridoma on the tumorigenicity of mouse myeloma cells.

A rabbit lymphocyte-mouse myeloma hybridoma (RX54-3) was administered to BALB/c mice, in order to determine whether hybridoma cells have any protective effect on the tumorigenicity of the P3X63/Ag8 mouse myeloma cell line, one of the parents of this hybridoma. Two sublines of RX54-3 were studied. (a) "new" cells, which produce rabbit light chains and mouse immunoglobulin, are killed by anti-myeloma cell antiserum and complement and possess a high chromosome count. And (b) "old" cells, which have lost all immunoglobulin-producing capacity, are no longer killed by anti-myeloma cell antiserum and complement and possess a low chromosome count. In contrast to myeloma cells, the hybridoma cells were nontumorigenic in normal BALB/c mice, even at very high cell doses. When hybridoma cells were administered prior to challenge with P3X63/Ag8 myeloma cells, protection against development of myeloma tumors was much more effective with new cells than with old cells. Development of protection was dependent on the dose of hybridoma cells, their route of administration, their viability and ability to divide, and the time interval between administration of the hybridoma and myeloma cells. The protection produced by the new hybridoma cells was comparable to that seen after administration of a subtumorigenic dose of living myeloma cells. With both the hybridoma and myeloma cells, protection was seen only against challenge with P3X63/Ag8 myeloma cells but not against another myeloma tumor. These studies indicate that administration of somatic cell hybrids is an effective method of protecting syngeneic hosts against challenge with mouse myeloma tumor cells.