**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.**
Luis del Pozo-Yauner
Department of Pathology - University of South Alabama College of Medicine
2451 University Hospital Drive, Moorer Building Rm 1520, Mobile, AL 36617
Email: ldelpozoyauner@health.southalabama.edu
Phone (Office): (251) 470 5863

**Main Body of the Abstract**
A fraction of patients with immunoglobulin light chain (AL) amyloidosis who achieve a good hematologic response still experience an unfavorable clinical evolution due to progressive organ damage resulting from preexisting AL deposits for which current therapies are ineffective. Therefore, there is growing interest in therapies aimed at removing AL deposits by enhancing physiological mechanisms such as enzymatic degradation, cellular uptake, and clearance by specialized macrophage-like cells. Antibodies are ideal for this purpose, given their unique recognition properties and biological functions. However, clinical trials so far conducted with pan-AL fibril monoclonal antibodies have had mixed results. Low affinity and/or poor access to the target epitope may be the cause of their reduced therapeutic efficacy in some AL patients, a consequence of the high structural heterogeneity of AL fibrils. We postulate that antibodies with specificities restricted to structurally related light chains, such as those belonging to the same variable domain (VL) subgroup, may be more suitable for anti-AL fibril therapies than pan-AL antibodies. Using a structural approach, we produced six rabbit polyclonal antibodies (Ab-A to F) by immunizing animals with nonoverlapping peptide segments of the recombinant lambda-6 VL protein 6aJL2. We demonstrated that these antibodies recognize monomers, oligomers, and misfolded amyloid fibrils of 6aJL2 but not the native proteins. Furthermore, they recognized amyloid-like fibrils of AL-derived lambda-6 light chains with little or no cross-reactivity with aggregates of other kappa and lambda proteins (Figure 1). These findings indicate that this approach can be used to obtain AL subgroup-specific antibodies with therapeutic applications.



Developing Conformation-Sensitive Antibodies Targeting Amyloid Aggregates of Lambda-6 Light Chains: A Structure-Based Approach for Therapeutic Intervention PA32 (#207)

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.