**Author Listing - Lead/ Submitting Author (we will be communicating with this individual): Name, Institution, City and State where the work was done. Co-authors will be added in a separate section.**
Lead/Submitting Author: Ricardo J. Antonia. Gate Bioscience. Brisbane, CA.

**Main Body of the Abstract**
The goal of Immunoglobulin Light Chain (AL) Amyloidosis treatment is the rapid reduction of serum free light chain levels. To assess whether novel therapies reduce serum free light chain levels, in vivo models are essential. Here, we engrafted cell lines expressing light chain variable domains typical in AL Amyloidosis patients into NOG mice and assayed for free light chain in their serum. ALMC-1 and ALMC-2 cell lines, from an AL patient that secrete IGLV6-57, and RPMI8226 and KHM-1B myeloma cell lines that secrete IGLV2-14 and IGLV1-44, respectively, were selected. Since amino acid sequence influences the secretion and clearance of light chain, bulk RNA sequencing confirmed the full light chain sequence in each cell line. Of the lines tested, only RPMI8226 exhibited robust free light chain levels when engrafted into NOG mice. Since ALMC-1/2 are the only immortalized cell lines derived from an AL patient, we sought ways to improve this xenograft model. We hypothesized that since ALMC-1/2 depend on exogenous IL-6, and murine IL-6 doesn't bind to human IL6R, that engrafting ALMC-1/2 cells into humanized IL-6 mice would lead to an improved model. Indeed, we observed that in humanized IL-6 NOG mice, ALMC-1/2 tumors grew faster, and the mice had higher serum free light chain levels. RNA sequencing of cells in culture revealed IL-6 induced up-regulation of anti-apoptotic genes, potentially explaining the IL-6 dependency in vivo. Overall, these data indicate that ALMC-1/2 xenografts in humanized IL-6 NOG serve as a promising model for therapeutic interventions in AL Amyloidosis.



**Author Listing - Lead/ Submitting Author (we will be communicating with this individual): Name, Institution, City and State where the work was done. Co-authors will be added in a separate section.**
Lead/Submitting Author: Ricardo J. Antonia. Gate Bioscience. Brisbane, CA.

**Main Body of the Abstract**
The goal of Immunoglobulin Light Chain (AL) Amyloidosis treatment is the rapid reduction of serum free light chain levels. To assess whether novel therapies reduce serum free light chain levels, _in vivo_ models are essential. Here, we engrafted cell lines expressing light chain variable domains typical in AL Amyloidosis patients into NOG mice and assayed for free light chain in their serum. ALMC-1 and ALMC-2 cell lines, from an AL patient that secrete IGLV6-57, and RPMI8226 and KHM-1B myeloma cell lines that secrete IGLV2-14 and IGLV1-44, respectively, were selected. Since amino acid sequence influences the secretion and clearance of light chain, bulk RNA sequencing confirmed the full light chain sequence in each cell line. Of the lines tested, only RPMI8226 exhibited robust free light chain levels when engrafted into NOG mice. Since ALMC-1/2 are the only immortalized cell lines derived from an AL patient, we sought ways to improve this xenograft model. We hypothesized that since ALMC-1/2 depend on exogenous IL-6, and murine IL-6 doesn't bind to human IL6R, that engrafting ALMC-1/2 cells into humanized IL-6 mice would lead to an improved model. Indeed, we observed that in humanized IL-6 NOG mice, ALMC-1/2 tumors grew faster, and the mice had higher serum free light chain levels. RNA sequencing of cells in culture revealed IL-6 induced up-regulation of anti-apoptotic genes, potentially explaining the IL-6 dependency _in vivo_. Overall, these data indicate that ALMC-1/2 xenografts in humanized IL-6 NOG serve as a promising model for therapeutic interventions in AL Amyloidosis.



Cell line xenografts to model serum free lambda light chain in vivo— a comparison of NOG vs humanized Interleukin 6 (IL-6) NOG mice PA27 (#130)

We invite you to attend the XIX International Symposium on Amyloidosis to be held in Rochester, MN.

This symposium is organized as a hybrid meeting (with the focus on in-person) held from Sunday, May 26 through Thursday, May 30, 2024.

Together with the ISA Board and members of Mayo Clinic, a very attractive scientific hybrid program is being planned. The program will cover a variety of types of systemic amyloidosis: ATTR (hereditary and wild-type), AL (light-chain), AA and less frequent forms. There will be key lectures, specific symposia including those company sponsored, oral presentations and poster sessions of accepted abstracts.

COURSE DESCRIPTION
This program will provide a comprehensive review of state-of-the-art education in systemic amyloidosis: basic science, pathophysiology, diagnosis, current and emerging treatments. Scientific presentations will include competitive oral and poster abstracts. The rapid evolution of scientific discovery and expanding treatment options has created tremendous interest in the field and this meeting will fill and important gap in educating scientists and clinicians.