RT Journal Article
T1 Therapeutic applications of a novel humanized monoclonal antibody targeting chemokine receptor CCR9 in pancreatic cancer
A1 McDonald, Hannah G.
A1 Reagan, Anna M.
A1 Bailey, Charles J.
A1 Gao, Mei
A1 Gao, Muqiang
A1 Solomon, Angelica L
A1 Cavnar, Michael J.
A1 Pandalai, Prakash K.
A1 Barry-Hundeyin, Mautin T.
A1 Harper, Megan M.
A1 Rueckert, Justin A.
A1 Turrero Braojos, Ángela
A1 Tobío Ageitos, Araceli
A1 Vidal Figueroa, Anxo
A1 Roca-Lema, Daniel
A1 Álvarez-Coiradas, Elia
A1 Garrido, Pablo
A1 Simón, Laureano
A1 Kim, Joseph
AB The relative failure of immune checkpoint inhibitors in pancreatic ductaladenocarcinoma (PDAC) despite having a dense, immunosuppressivetumor microenvironment highlights the need to target alternate/escapepathways. We have previously examined C–C chemokine receptor type 9(CCR9) as a candidate immune checkpoint and developed a targeted,humanized monoclonal antibody (SRB2). Cytotoxicity of SRB2 was evalu-ated in vitro and in vivo. CCR9 expression on PDAC cells/tissues, immunecomponents of patient-derived organoids (PDOs), and antibody-dependentcell-mediated cytotoxicity were examined. In PANC-1 and MIA PaCa-2cell lines, we demonstrated highest CCR9 expression; however, no directcytotoxic effect was observed with SRB2 treatment. In PANC-1 cells, NKcell-mediated cytotoxicity was promoted by SRB2. Dose-dependent SRB2cytotoxicity was observed in PDAC PDOs. In patient-derived xenograftmouse models, cytotoxicity of SRB2 monotherapy and in combination withoxaliplatin was also shown. In humanized immune-competent mousemodels, SRB2 efficacy was similar to other drugs, but two mice in thiscohort had complete tumor regression. Our current studies suggest thattherapeutic targeting of CCR9 may improve PDAC outcomes, and addi-tional studies are underway to evaluate SRB2 for clinical use.
PB Wiley
SN 1878-0261
YR 2025
FD 2025-05-13
LK https://hdl.handle.net/10347/42386
UL https://hdl.handle.net/10347/42386
LA eng
NO McDonald, H.G., Reagan, A.M., Bailey, C.J., Gao, M., Gao, M., Solomon, A.L., Cavnar, M.J., Pandalai, P.K., Barry-Hundeyin, M.T., Harper, M.M., Rueckert, J.A., Turrero, Á., Tobio, A., Vidal, A., Roca-Lema, D., Álvarez-Coiradas, E., Garrido, P., Simón, L. and Kim, J. (2025), Therapeutic applications of a novel humanized monoclonal antibody targeting chemokine receptor CCR9 in pancreatic cancer. Mol Oncol. https://doi.org/10.1002/1878-0261.70062
NO This research was supported by NIH Training Grant T32CA160003 (HGM, AMR, and MMH), the Biospecimen Procurement and Translational Pathology Shared Resource, and the Flow Cytometry and Immune Monitoring Shared Resource of the University of Kentucky Markey Cancer Center.
DS Minerva
RD 24 abr 2026