Program/Event
Undergraduate Summer Research Showcase Summer 2023, Research Louisville 2023, Brown Cancer Center Retreat 2023
Abstract
Melanoma is the fifth most common cancer in the US, with limited effective immunotherapeutic options available for patients. Avaren-Fc (AvFc) is a novel experimental immunotherapeutic agent with a unique “lectibody” property. It is capable of targeting cancer cells through the selective recognition of high mannose glycans, which are aberrantly overrepresented on the surface of malignant cells. Upon binding to cancer cells, AvFc can interact with circulating effector immune cells equipped with Fc receptors, such as natural killer (NK) cells to induce antibody-dependent cell-mediated cytotoxicity (ADCC) and kill the cancer cells. Previous work has shown that AvFc effectively induces ADCC activity against B16F10 cancer cells in vitro. Furthermore, flow cytometry analysis revealed that AvFc treatment exhibited a trend towards increased NK cell infiltration within the B16F10 flank tumor tissue of C57bl/c mice.
The objective of the current study is to assess the B16F10 tumor microenvironment by immunohistochemistry (IHC), quantifying NK cells and an associated NK cell activation signal in AvFc-treated B16F10 tumor tissue compared to untreated tissue. Based on our previous observation in the flow cytometry analysis, we hypothesized that AvFc-treated tissue may have an elevated NK cell count, indicative of AvFc-mediated recruitment of NK cells.
The study utilized fluorescent IHC, which probed for NK cells (NK1.1) and NK cell activation (CD107a). The results demonstrated a significant increase in the number of NK-1.1+ cells (p = 0.0056, Wilcoxon Rank Sum Test) and CD107a+ signal (p = 0.0009, Wilcoxon Rank Sum Test) in AvFc-treated tissue when compared to untreated tissue. Furthermore, colocalization of NK-1.1 and CD107a was also deemed significant in AvFc-treated tissue (p = 0.0032, Wilcoxon Rank Sum Test), thus supporting the presence and associated activation of NK cells in the tumor microenvironment.
These results warrant further analysis to elucidate the underlying mechanism by which AvFc recruits additional NK cells to the tumor tissue. Overall, the results from this study corroborate that AvFc’s anti-cancer activity is mediated via NK cell activation and supports its development as a potential immunotherapeutic for melanoma treatment.
Recommended Citation
Vemuri, Sreevatsa; Mayer, Katarina L; and Matoba, Nobuyuki
(2024)
"Avaren-Fc, a Novel Immunotherapeutic, Recruits NK Cells in B16F10 Melanoma Tumor Tissue,"
The Cardinal Edge: Vol. 2:
Iss.
2, Article 3.
Available at:
https://ir.library.louisville.edu/tce/vol2/iss2/3
Included in
Medical Immunology Commons, Pharmaceutics and Drug Design Commons, Skin and Connective Tissue Diseases Commons, Translational Medical Research Commons
