Abstract A08: Distribution, cutoff, and functional significance of a potential biomarker for Imprime PGG, an experimental cancer immunotherapeutic, in a healthy subject population
| Autor: | Nadine Ottoson, Adria Jonas, Xiaohong Qiu, Richard Walsh, Nandita Bose, Diane McMurray, Lindsay R. Wurst, Steven M. Leonardo, Ben Harrison, Peter Maimonis, Katie Ertelt |
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| Rok vydání: | 2015 |
| Předmět: | |
| Zdroj: | Cancer Immunology Research. 3:A08-A08 |
| ISSN: | 2326-6074 2326-6066 |
| DOI: | 10.1158/2326-6074.tumimm14-a08 |
| Popis: | Imprime PGG (Imprime) is a yeast-derived beta-1,3/1,6 glucan that binds complement receptor 3 (CR3) on innate immune cells and enables these cells to exert anti-tumor activity against tumor cells that have been opsonized by iC3b following targeting by anti-tumor antibodies. Following incubation with whole blood (WB) from healthy subjects, Imprime was shown to bind to neutrophils and monocytes via CR3 and modulate complement receptor expression, activation marker expression, and interleukin-8 (IL-8) production. These effects, however, differed widely among subjects. It was subsequently observed that Imprime-induced functional activities occurred predominantly in individuals with higher levels of endogenous immunoglobulin G (IgG) or IgM anti-beta-glucan antibodies (ABA) and that ABA are a prerequisite for opsonizing Imprime to allow its binding to CR3. A small pilot study (n=32) with healthy subjects using prototype enzyme-linked immunosorbent assays (ELISAs) to measure IgG and IgM ABA suggested correlations between ABA levels, Imprime binding to neutrophils in WB, and consequent induction of functional responses. The objectives of this study were to further optimize and qualify the prototype ELISAs and, in a larger cohort of healthy subjects (n=143), to confirm the significance of elevated ABA levels with respect to binding of Imprime to neutrophils and monocytes and Imprime–induced functional changes. Qualification of the IgG and IgM ABA ELISAs yielded good inter-assay precision (coefficients of variation 5% of cells) in samples from 52% of the subjects. Samples from these same subjects also exhibited high Imprime binding to monocytes. ABA levels in the high binding individuals were significantly greater than those in the low binding individuals (p Citation Format: Diane McMurray, Ben Harrison, Katie Ertelt, Richard Walsh, Lindsay Wurst, Steven Leonardo, Nadine Ottoson, Adria Bykowski Jonas, Xiaohong Qiu, Nandita Bose, Peter Maimonis. Distribution, cutoff, and functional significance of a potential biomarker for Imprime PGG, an experimental cancer immunotherapeutic, in a healthy subject population. [abstract]. In: Proceedings of the AACR Special Conference: Tumor Immunology and Immunotherapy: A New Chapter; December 1-4, 2014; Orlando, FL. Philadelphia (PA): AACR; Cancer Immunol Res 2015;3(10 Suppl):Abstract nr A08. |
| Databáze: | OpenAIRE |
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