Tumor‐antigen‐specific humoral immune response of animals to anti‐idiotypic antibodies and comparative serological analysis of patients with small‐cell lung carcinoma

Abstract

We have previously developed 3 monoclonal anti-idiotypic antibodies (Ab2) of LOU rat origin directed against the binding site of the murine monoclonal IgM LAM8, which recognizes the small-cell lung carcinoma (SCLC)-associated sialoglycoprotein antigen sGP 90-135. The aim of this study was to compare the efficiencies of these 3 Ab2, designated LY8-229, LX8-531 and LX8-632, to induce antigen-specific immunity in different animal species without prior exposure of the recipients to the nominal antigen, and thereby possibly select an Ab2 candidate for active immunotherapy against SCLC in patients. The feasibility of this approach was further evaluated by a serological analysis of patients with SCLC compared with healthy individuals, in whom the spontaneous antibody reactivities against SCLC cell lines and Ab2 were tested. LY8-229 was shown to be the most effective Ab2 in inducing antigen-specific antibodies in BALB/c mice, CBA/J/Zur mice and one NZW rabbit. Furthermore, LY8-229 was the only Ab2 against which significantly elevated idiotype-specific antibody reactivities existed in sera of patients with SCLC. These reactivities correlated positively with binding to antigen-positive tumor cells. Our findings suggest that LY8-229 represents in its reactivity pattern the nominal SCLC antigen in humans also, and therefore may be of diagnostic and possibly therapeutic relevance for patients with SCLC.

Pulmonary perspective: immunology in diagnosis and treatment of lung cancer

“…In addition, an idiotype-specific antibody reactivity was recently reported against this Ab2 in the sera of SCLC patients. This suggests that this Ab2 (LY8-229) represents a nominal SCLC antigen and, therefore, should be a candidate for active immunotherapy in SCLC patients [77].…”

Third international workshop on lung tumor and differentiation antigens: Overview of the results of the central data analysis

“…Cluster-5 and -5A antigens are co-expressed in SCLC cell lines and tissues, but the molecular relationship has long remained undefined. Evidence for the simultaneous expression of the cluster-5 and cluster-5A epitopes on a single membrane molecule which is shed in low quantities into the serum of patients with SCLC has been obtained by immunological means using (a) a mouse anti-anti-idiotype MAb generated against a rat anti-idiotype MAb in the cluster-5 system (Lehmann et a/., 1992) and (b) by a heterologous cluster-5 and cluster-5A antibody sandwich assay in sera of patients with SCLC (Lehmann et al, this Supplement). The effectiveness of a cluster-5A immunotoxin against SCLC in vitro and in vivo has been demonstrated by Zangemeister-Wittke et al (1993~).…”

Internal image anti‐idiotype antibodies related to renal‐cell carcinoma‐associated antigen G250

“…The unequal Abl' induction can also be explained by poor immunogenicity. Lehmann et al (1992) reported that Abl' induction may vary, and vaccination with otherwise indistinguishable internal-image Ab2s may not result in Abl' production, suggesting the existence of subtle differences between internal-image Ab2s (Chattopadhyay et aL, 1991). Alternatively, unmodified anti-idiotype mouse IgG may be poorly immunogenic.…”