Mimicry of the Hodgkin-Associated IRAC Antigen by an Anti-Idiotype Network: Potential Use in Active Immunotherapy of Hodgkin's Lymphoma

The murine monoclonal antibody anti-IRac, defining a surface-antigen structure (MW 70 kDa) on Hodgkin-Reed-Sternberg and interdigitating reticulum cells, was used to generate a cascade of anti-idiotypic antibodies as well as a cellular immunity against Hodgkin-Reed-Sternberg cells in syngeneic BALB/c-mice. The anti-idiotypic antibody monoclonal antibody 4B4 demonstrated characteristics of an "internal image" or network antibody (Ab2 beta). Ab2 beta 4B4 bound specifically to anti-IRac and inhibited anti-IRac-binding to antigen-bearing cells effectively. 4B4 induced an IRac-specific humoral polyclonal immune response in BALB/c-mice and New Zealand white rabbits as judged by Flow cytometric and histochemical analysis. Moreover, BALB/c-mice immunized with 4B4 showed statistically significant (p > 0.01) delayed-type hypersensitivity reaction against IRac-expressing Hodgkin cell-lines. Ab2 beta 4B4 induced in syngeneic BALB/c mice a monoclonal anti-anti-idiotypic antibody (Ab3) termed 3G10, which mimicked the specificities of Ab1 anti-IRac and thus confirms the internal image nature of Ab2 beta 4B4. The anti-idiotype-induced tumor cell specific T- and B-cell mediated immune response even across species barriers via the Hodgkin related IRac-antigen may play an important part in active specific immunotherapy of Hodgkin's disease.