Abstract. Antibody responses to tumor antigens play an important role in initiating a cellular antitumor response with respect to antigen cross-presentation and T cell cross-priming. Successful vaccination strategies rely on an optimally timed activation of the humoral and cellular immune system by using appropriate adjuvant stimulation. The LUD99-008 trial used the cancer testis antigen NY-ESO-1 formulated with ISCOMATRIX adjuvant injected into patients intramuscularly. It was shown that this vaccination strategy is a safe and highly potent activator of the humoral and cellular immune system. Using the RAYS technology, we analyzed in detail the humoral immune response in these patients before and after vaccination: during the course of repeated vaccinations with the adjuvant, antibody titers against NY-ESO-1 and cross-reactivity to LAGE 1A and B increased as an indicator of an enhanced immune response, whereas no antibody response could be detected after vaccination without the adjuvant. Analysis of single fragments of the NY-ESO-1 protein revealed that the humoral response was almost exclusively directed against the N-terminal fragments and the number of fragments and their length being recognized by the NY-ESO-1-specific antibodies increased during the course of vaccination. The humoral immune response mainly consisted of antibodies of the IgG1 and IgG3 subclass. We rarely found IgG2 and IgG4 subclass antibodies. Our results support the implication that targetspecific antibodies raised after vaccination contribute to the stimulation of an effective T cell response against the target antigen. IntroductionBesides surgery, chemotherapy and radiation therapy, immunotherapy has emerged in the past decade as supplementary approach to fight cancer (1). Due to its specificity and efficacy, immunotherapy ideally targets the tumor selectively and spares normal tissue. A prerequisite in the field of cancer immunotherapy is the identification and characterization of appropriate target antigens for therapeutic approaches. In modern tumor serology, the powerful SEREX-technology (serological identification of antigens by recombinant expression cloning) allowed for the identification of a multitude of new cancer antigens in various tumor entities by screening of tumor-derived gene expression libraries with high-titered IgG antibodies obtained from the sera of cancer patients. The international SEREX database (www2.licr.org/Cancer ImmunomeDB/) by now holds >2000 different gene entries of potentially cancer related antigens. One group of antigens, the so-called cancer/testis antigens (CTAs) has gained special interest among the characterized tumor-specific antigens, as they are only expressed in the immunologically privileged germline cells and various types of human cancers but not in normal tissue (2-4). Of particular interest in this regard is the CTA NY-ESO-1. It is the most immunogenic CTA discovered so far and frequently elicits spontaneous humoral and cellular immune responses in patients with NY-ESO-1 expressing tumors...
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.