Heteroantisera against interferon (IFN) and interleukin-2 (IL-2) are highly immunosuppressive when injected into experimental animals. These anticytokines impair the generation of cytolytic T cells, the rejection of transplanted tumors, and other cellular immune functions. Murine monoclonal antibodies against IL-2 have been available for several years, and recently the technology for the generation of human monoclonal antibodies has emerged. Patients treated with IFN in various clinical trials and patients with systemic lupus erythematosis with high endogenous levels of IFN develop antibodies against IFN. Similarly, patients repeatedly injected with recombinant IL-2 as treatment for refractory cancer develop IgG antibodies against IL-2. We propose to generate human hybridomas from the B-lymphocytes of these patients by fusion with human myeloma cell lines. The culture supernatants of these hybridomas will be screened for anti-IL-2 antibodies with a sensitive ELISA and subsequently for the ability to inhibit IL-2-induced T-cell proliferation, cytolytic T-cell induction, and the development of a delayed-type hypersensitivity response to tuberculin. These neutralizing antibodies may be clinically useful in the prevention and treatment of organ allograft rejection and in the treatment of certain T-cell malignancies.National Cancer Institute (NCI)
