Documentation of Idiotypic Cascade after Lym-1 Radioimmunotherapy in a Patient with Non-Hodgkin’s Lymphoma Basis for Extended Survival?

Purpose: The purpose of this study was to examine idiotypic cascade mechanisms in the plasma of a prolonged survivor patient with aggressive non-Hodgkin’s lymphoma (NHL). It is a follow-up to previously published seminal studies by this laboratory showing survival benefit associated with radioimmunotherapy in NHL patients. Immunoglobulin from the patient’s plasma was purified, characterized, and shown to possess the activities expected of idiotypic antibodies. Experimental Design: Plasma from a NHL patient treated with Lym-1 was precipitated with ammonium sulfate and octanoic acid, followed by immunoadsorbant chromatography with solid phase Lym-1 monoclonal antibody to purify Ab2. The last purification step involved the binding of Ab3 to glutaraldehyde-fixed Raji cells, followed by acid elution of Ab3. Proteins were quantified and characterized. Antibody-dependent cellular cytotoxicity activity was determined using a standard 51 Cr release assay. Results: Purified immunoglobulin populations exhibited the characteristics of Ab2β and Ab3 antibodies. Both showed ability to compete with the binding of Lym-1 to its tumor cell target, and Ab3 showed ability to induce antibody-dependent cellular cytotoxicity. Conclusions: This study offers direct evidence for initiation of a multilevel idiotypic cascade in a patient undergoing passive monoclonal antibody therapy for NHL. The patient’s prolonged disease-free survival may, thus, be understood in the context of the generation of endogenous, self-perpetuating tumor-specific antibodies.