**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.**
Manasi Balachandran, Ph.D.
Assistant Professor 
Amyloidosis and Cancer Theranostics Program 
Graduate School of Medicine 
The University of Tennessee Medical Center 
Knoxville, Tennessee

**Main Body of the Abstract**
Background: Chimeric antigen receptor-macrophages have been generated that express the p5 pan-amyloid-reactive peptide to facilitate amyloid clearance. Cell-based therapies do not have targeting capabilities but accumulate in sites of inflammation. Amyloid is a non-inflammatory pathology; however, we have observed trafficking of macrophages to the kidney in a murine model of AA amyloidosis. Here, we describe the temporal changes in cytokine levels during the development of AA amyloidosis, that contribute to this phenomenon.
Methods: Cohorts of H2/IL-6 mice were administered AEF intravenously (n=3/group). At time 0 and 1, 3, and 5 wk post-AEF serum and organ samples (kidney, liver, and spleen) were harvested. Cytokine levels were quantified by flow cytometry (Legendplex Kit). Tissues were fixed in formalin, sectioned, and stained with Congo red and H&E, and the macrophage markers Iba-1, and CD68.
Results: In the kidneys we observed a significant increase in pro-inflammatory cytokines [CXCL1 (p<0.0001), CXCL10 (p<0.0001), TNF-α (p<0.0010), CCL2 (p<0.0033)] between wk 1 and 3 post-AEF, concurrent with the progressive deposition of amyloid (Fig. 1A). This also coincided with an increase in Iba-1-positive macrophages in the kidney over the initial 3 weeks post-AEF (Fig. 1B). At wk 5 post-AEF renal cytokine levels were normal.  No significant changes in organ-related cytokine production were seen in the liver or spleen.
Conclusion: Renal amyloid formation in the mouse resulted in a pro-inflammatory response leading to recruitment of monocytes. Consequently, amyloid-reactive CARM may be beneficial in patients with renal amyloid, and potentially also cardiac disease when a pro-inflammatory environs is established.



**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.**
Manasi Balachandran, Ph.D.
Assistant Professor 
Amyloidosis and Cancer Theranostics Program 
Graduate School of Medicine 
The University of Tennessee Medical Center 
Knoxville, Tennessee

**Main Body of the Abstract**
**Background:** Chimeric antigen receptor-macrophages have been generated that express the p5 pan-amyloid-reactive peptide to facilitate amyloid clearance. Cell-based therapies do not have targeting capabilities but accumulate in sites of inflammation. Amyloid is a non-inflammatory pathology; however, we have observed trafficking of macrophages to the kidney in a murine model of AA amyloidosis. Here, we describe the temporal changes in cytokine levels during the development of AA amyloidosis, that contribute to this phenomenon.
**Methods:** Cohorts of H2/IL-6 mice were administered AEF intravenously (n=3/group). At time 0 and 1, 3, and 5 wk post-AEF serum and organ samples (kidney, liver, and spleen) were harvested. Cytokine levels were quantified by flow cytometry (Legendplex Kit). Tissues were fixed in formalin, sectioned, and stained with Congo red and H&E, and the macrophage markers Iba-1, and CD68.
**Results:** In the kidneys we observed a significant increase in pro-inflammatory cytokines [CXCL1 (_p_<0.0001), CXCL10 (_p_<0.0001), TNF-α (_p_<0.0010), CCL2 (_p_<0.0033)] between wk 1 and 3 post-AEF, concurrent with the progressive deposition of amyloid (Fig. 1A). This also coincided with an increase in Iba-1-positive macrophages in the kidney over the initial 3 weeks post-AEF (Fig. 1B). At wk 5 post-AEF renal cytokine levels were normal.  No significant changes in organ-related cytokine production were seen in the liver or spleen.
**Conclusion:** Renal amyloid formation in the mouse resulted in a pro-inflammatory response leading to recruitment of monocytes. Consequently, amyloid-reactive CARM may be beneficial in patients with renal amyloid, and potentially also cardiac disease when a pro-inflammatory environs is established.



Temporal Changes in the Renal Cytokine Profile in Response to AA Amyloidosis Induce Macrophage Infiltration Enabling Host-Mediated Targeting of Therapeutic Chimeric Antigen Receptor Macrophages (CARM) PA40 (#294)

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.