Henry Ford Health + Michigan State University Health Sciences researchers are tackling one of the deadliest cancers, pancreatic ductal adenocarcinoma (PDAC), the most common type of pancreatic cancer. With a 5-year survival rate of 12%, Xuefei Huang, Ph.D., Michigan State University Departments of Biomedical Engineering and Chemistry professor, and Howard Crawford, Ph.D., Henry Ford Health Pancreatic Cancer Center scientific director, are collaborating to address the lack of effective pancreatic cancer treatment and develop novel therapeutics against this disease.
"What inspires me about this partnership is the opportunity to work with world-renowned researcher Dr. Crawford on pancreatic cancer," shared Huang. "My group’s expertise is more on the chemistry and engineering side for immunotherapy development. Dr. Crawford brings in the critical expertise on pancreatic cancer, which is highly complementary."
In 2022, Huang and Crawford were awarded a $82,720 grant from the Henry Ford + MSU 2022 Cancer Seed Funding Program. Their joint grant submission proposed that, "...antibody-based immunotherapy would complement well with current pancreatic treatment methods of surgery, radiation and chemotherapy."
Thus, Howard and Huang are working to develop novel antibodies against Sialyl Lewis A (sLea), a biomarker for pancreatic cancer that highly impacts the pancreatic cancer development and metastasis (the spread of cancer cells).
"Pancreatic cancer is a dismal disease, with most patients passing away within 9 months of diagnosis," said Howard. "Basic science takes time to translate to the clinic, but these patients do not have the luxury of time."
To develop these new antibodies, the researchers are utilizing the past two decades of work from Huang’s laboratory on the development of new immunogenic carriers (immune response) for anti-cancer vaccine development with bacteriophage qbeta (Qβ) (a type of virus that infects bacteria).
"We have exciting results demonstrating that immunization with the conjugate of bacteriophage Qβ with sLea could induce high levels and long-lasting IgG antibodies against sLea, which recognized sLea positive tumor cells and reduced tumor development in a tumor metastasis model in mice," explained Huang.
During the research and testing, Huang’s lab focuses on the conjugate design and mAb (monoclonal antibody, a drug that recognizes and finds specific proteins on cancer cell) generation. Then Crawford’s lab is responsible for "generating the pancreatic cancer model and evaluating the treatment efficacy."
"We have encountered several unexpected challenges," said Huang. "Our initial efforts to generate nanobodies, a special type of antibody from llama, have not been successful yet due to the difficulties in enriching for the antibody. We have now switched to use mice to generate monoclonal antibodies."
Howard and Huang are currently analyzing the antibodies produced through immunization of mice and rabbits with the bacteriophage Qβ-sLea conjugate. In the next six months, they expect to complete the process of generating monoclonal antibodies. It is then these antibodies that will be used against the biomarker for pancreatic cancer, sLea.
"By developing new anti-sLea mAbs, our work can expand the toolchest, provide effective alternatives to current treatments for pancreatic cancer, and broaden the access to diagnostic and therapeutic agents against this cancer to the community," said Howard.
Henry Ford + MSU has announced the pilot grant recipients of the 2023 Cancer Seed Funding Program and will announce later in 2023 the integration grants.