Posters
Presentation Type
Poster
Discipline Track
Translational Science
Abstract Type
Research/Clinical
Abstract
About 95% of tumor arises from epithelial cell lining ducts known to be pancreatic ductal adenocarcinomas, with less than 5-7% survival rate. Unfortunately, little progress has been seen in the outcomes of patients with PDAC as tumor develops high desmoplasia and chemo-resistance to chemotherapeutic drugs, such as gemcitabine (Gem). Immunotherapy has shown promising results in cancers, except pancreatic cancer due to their characteristic fibrotic tumor microenvironment. The therapies are unable to penetrate to the fibrotic tumors leading to insufficient availability of the therapeutic drugs at the tumor site. A recently identified mucin, MUC13 is aberrantly expressed in pancreatic tumors but not in normal pancreas. This makes MUC13 as an excellent protein for specifically targeting pancreatic tumors. In this project, we demonstrate a unique ability of our in-house generated mouse and humanized monoclonal antibody of MUC13 to penetrate and target pancreatic cancer. These antibodies have been conjugated with our recently developed novel patented superparamagnetic iron oxide nanoparticles (SPIONS). The aim of our study is to deliver stroma targeting drugs efficiently to pancreatic tumors that would soften the tumors to improve the response of checkpoint immunotherapies. The stroma targeting drugs used are curcumin and AMD3100, which are both in clinical trials for human use. This study is unique as it will utilize MUC13 antibodies for targeting the pancreatic tumor site and SPION nanoparticle system for delivering the stroma depleting drugs, which would help in improving immunotherapy response. Our results demonstrate that our MUC13 antibody conjugated SPIONS can efficiently internalize the PDAC cells. SPION-MUC13 using Indocyanine dye (ICG) specifically reached to the tumor site in an orthotopic pancreatic cancer model as indicated by ICG fluorescence. MUC13-SPION formulation led to an enhanced uptake in MUC13 positive (MUC13+) PanCa cells, compared with MUC13 null (MUC13-) cells as demonstrated by immunofluorescence, Prussian blue staining and flow cytometry experiments. Interestingly, the formulation resulted in sustained delivery of curcumin (CUR), enhanced inhibition of cell proliferation, migration and invasion in MUC13+ cells as compared with MUC13- cells, which suggests the targeting efficacy of the formulation. Additionally, the treatment of cells with the formulation inhibited the tumor spheroid formation and growth. The formulation softens up the tumors for therapies that can result in improved response to checkpoint immunotherapies. Therefore, this study indicates high significance of MUC13-SPIONS for achieving pancreatic tumor specific delivery of drugs. Efficient MUC13 conjugated SPION-CUR can potentiate checkpoint immunotherapies, inhibit tumor growth and its progression, which will be conducted in continuation in a pancreatic orthotopic mice model. This study has a potential to reduce morbidity and mortality caused by the disease and improve survival in patients.
Academic/Professional Position
Graduate Student
Mentor/PI Department
Immunology and Microbiology
Recommended Citation
Shaji, Poornima Devi; Jaggi, Meena; Yallapu, Murali M.; Chauhan, Subhash C.; and Khan, Sheema, "Antibody Mediated Targeted Drug Delivery System To Improve Immunotherapy In Pancreatic Cancer" (2023). Research Symposium. 17.
https://scholarworks.utrgv.edu/somrs/theme1/posters/17
Antibody Mediated Targeted Drug Delivery System To Improve Immunotherapy In Pancreatic Cancer
About 95% of tumor arises from epithelial cell lining ducts known to be pancreatic ductal adenocarcinomas, with less than 5-7% survival rate. Unfortunately, little progress has been seen in the outcomes of patients with PDAC as tumor develops high desmoplasia and chemo-resistance to chemotherapeutic drugs, such as gemcitabine (Gem). Immunotherapy has shown promising results in cancers, except pancreatic cancer due to their characteristic fibrotic tumor microenvironment. The therapies are unable to penetrate to the fibrotic tumors leading to insufficient availability of the therapeutic drugs at the tumor site. A recently identified mucin, MUC13 is aberrantly expressed in pancreatic tumors but not in normal pancreas. This makes MUC13 as an excellent protein for specifically targeting pancreatic tumors. In this project, we demonstrate a unique ability of our in-house generated mouse and humanized monoclonal antibody of MUC13 to penetrate and target pancreatic cancer. These antibodies have been conjugated with our recently developed novel patented superparamagnetic iron oxide nanoparticles (SPIONS). The aim of our study is to deliver stroma targeting drugs efficiently to pancreatic tumors that would soften the tumors to improve the response of checkpoint immunotherapies. The stroma targeting drugs used are curcumin and AMD3100, which are both in clinical trials for human use. This study is unique as it will utilize MUC13 antibodies for targeting the pancreatic tumor site and SPION nanoparticle system for delivering the stroma depleting drugs, which would help in improving immunotherapy response. Our results demonstrate that our MUC13 antibody conjugated SPIONS can efficiently internalize the PDAC cells. SPION-MUC13 using Indocyanine dye (ICG) specifically reached to the tumor site in an orthotopic pancreatic cancer model as indicated by ICG fluorescence. MUC13-SPION formulation led to an enhanced uptake in MUC13 positive (MUC13+) PanCa cells, compared with MUC13 null (MUC13-) cells as demonstrated by immunofluorescence, Prussian blue staining and flow cytometry experiments. Interestingly, the formulation resulted in sustained delivery of curcumin (CUR), enhanced inhibition of cell proliferation, migration and invasion in MUC13+ cells as compared with MUC13- cells, which suggests the targeting efficacy of the formulation. Additionally, the treatment of cells with the formulation inhibited the tumor spheroid formation and growth. The formulation softens up the tumors for therapies that can result in improved response to checkpoint immunotherapies. Therefore, this study indicates high significance of MUC13-SPIONS for achieving pancreatic tumor specific delivery of drugs. Efficient MUC13 conjugated SPION-CUR can potentiate checkpoint immunotherapies, inhibit tumor growth and its progression, which will be conducted in continuation in a pancreatic orthotopic mice model. This study has a potential to reduce morbidity and mortality caused by the disease and improve survival in patients.