ANTI-VECTOR IMMUNOGLOBULIN INDUCED BY RETROVIRAL VECTORS

Replication-incompetent retroviruses have been employed as gene therap y vectors in experimental settings for more than a decade. More recent ly, these vectors have been tested in the clinic as inmunotherapeutic agents and anticancer agents. One potential problem with the use of su ch vectors is the possible development of immune responses directed ag ainst the vector particles themselves. Here, we examine immunoglobulin (Tg) responses specific for retroviral vectors derived from murine le ukemia virus (MLV). Anti-MLV Ig is seen following intramuscular (i.m.) administration of retroviral vectors in mice, and in nonhuman primate s; as expected, these responses are dependent upon the vector dose del ivered. Furthermore, serum from vector-treated animals is capable of p artially neutralizing vector-mediated transduction of target cells in an in vitro assay. Nevertheless, even in the presence of significant l evels of anti-vector Ig in vivo, i.m. administration of retroviral vec tor is still capable of driving both Ig and cytotoxic T lymphocyte (CT L) responses specific for vector-encoded gene products. This work sugg ests that although retroviral vectors may readily induce immune respon ses directed against the vector particles themselves, such responses w ill not significantly affect the efficiency of these vectors in an imm unotherapeutic protocol.