TL;DR: Thirty patients with advanced colorectal carcinoma were treated with alum-precipitated polyclonal goat anti-idiotypic antibodies to monoclonal anti-CRC antibody CO17-1A in doses between 0.5 and 4 mg per injection, and all patients developed anti-anti-identical antibodies (Ab3) with binding specificities on the surfaces of cultured tumor cells similar to the specificity of Ab1.
Abstract: Thirty patients with advanced colorectal carcinoma (CRC) were treated with alum-precipitated polyclonal goat anti-idiotypic antibodies (Ab2) to monoclonal anti-CRC antibody CO17-1A (Ab1) in doses between 0.5 and 4 mg per injection. All patients developed anti-anti-idiotypic antibodies (Ab3) with binding specificities on the surfaces of cultured tumor cells similar to the specificity of Ab1. Furthermore, the Ab3 competed with Ab1 for binding to CRC cells. Fractions of Ab3-containing sera obtained after elution of the serum immunoglobulins from CRC cells bound to purified tumor antigen and inhibited binding of Ab2 to Ab1. The Ab3, therefore, may share idiotopes with Ab1. Six patients showed partial clinical remission and seven patients showed arrest of metastases following immunotherapy. Four of the thirteen patients with measurable clinical responses had received Ab2 alone, whereas 9 patients had also received chemotherapy.
TL;DR: Since each receptor molecule carries associated with its specific antigen-binding site specific antigenic determinants (so-called idiotopes) that distinguish it from, and can be recognized by, other receptor molecules, it appears possible that the immune system regulates itself by internal receptor-receptor interactions.
Abstract: The function of the immune system is based on a large variety of receptor molecules that differ in their binding specificity. These receptors are located in part on the surfaces of the immunocompetent cells, namely, T and B lymphocytes, and in part appear free in the circulation. They mediate the specific recognition of antigens and guarantee the specificity of the immunologic reactions that follow antigen recognition. In addition, since each receptor molecule carries associated with its specific antigen-binding site specific antigenic determinants (so-called idiotopes) that distinguish it from, and can be recognized by, other receptor molecules, it appears possible that the immune system regulates itself by internal receptor-receptor interactions (Jerne, 1974).
TL;DR: Fusions with this line provide the potential for recovering many different species of idiotype in a mixed population, and will facilitate the production of mouse monoclonal anti-idiotype antibodies against many variants and against different idiotopes.
TL;DR: Measurement of the median lethal dose of the bacteria indicated that anti-idiotope immunization significantly increased the resistance of BALB/c mice to the bacterial challenge.
Abstract: A monoclonal anti-idiotope antibody coupled to a carrier protein was used to immunize BALB/c mice against a lethal Streptococcus pneumoniae infection. Vaccinated mice developed a high titer of antibody to phosphorylcholine, which is known to protect against infection with Streptococcus pneumoniae. Measurement of the median lethal dose of the bacteria indicated that anti-idiotope immunization significantly increased the resistance of BALB/c mice to the bacterial challenge. Antibody to an idiotope can thus be used as an antigen substitute for the induction of protective immunity.
TL;DR: Use of this system should significantly advance the analysis of the structural bases for both idiotype expression and antigen binding by immunoglobulin, and provide a generic method for the high-level expression of antibodies of diverse interest.
Abstract: A murine immunoglobulin heterodimer has been expressed in a baculovirus expression system. This was achieved by using both double infection of insect cells with separate heavy- and light-chain-expressing viruses and infection with a double-recombinant virus containing both the immunoglobulin heavy- and light-chain cDNAs. In both cases, the polypeptide chains were correctly processed, glycosylated, and assembled into normal H2L2 (H = heavy, L = light) immunoglobulin monomers. These molecules bound antigen and expressed both polyclonal idiotype and monoclonal idiotopes. Furthermore, the transfer vectors described have been modified to contain the F1 origin of replication for the production of single-stranded DNA, which facilitates site-specific mutations of either the polyhedrin promoter or the inserted foreign gene. Use of this system should significantly advance the analysis of the structural bases for both idiotype expression and antigen binding by immunoglobulin. More importantly, it provides a generic method for the high-level expression of antibodies of diverse interest.