Combining a monoclonal antibody against the MUC1 protein with two other immunotherapies may be a promising approach to treat MUC1-positive pancreatic cancers, according to recent preclinical data presented at the AACR Special Conference on Tumor Immunology and Immunotherapy Oct. 20-23 in Boston.
The study was conducted by researchers at the Eppley Institute for Cancer and Allied Disease at the University of Nebraska Medical Center under the direction of Dr. Michael Hollingsworth.
“The pancreatic cancer market is among the highest unmet therapy needs within the overall oncology market,” Dr. Madi Madiyalakan, CEO of Quest PharmaTech and OncoQuest, said in a press release.
“OncoQuest’s combinatory immunotherapy technology has the potential to help cancer patients generate a clinically meaningful immune response to the disease, which is being investigated with our lead product, oregovomab, in ovarian cancer,” Madiyalakan said. “We are encouraged by the positive preclinical results, which will help guide on the clinical development of our second product using our anti-MUC1 antibody, AR20.5, as a therapeutic treatment for pancreatic cancer.”
MUC1 is a key protein in cancer development and progression. It’s involved in tumor growth, metastatis formation, resistance to anti-cancer drugs, and maintenance of the “stemness” in cancer stem cells.
A large number of tumors express this protein at their surface, including pancreatic, lung, breast, colon, and prostate cancers, as well as multiple myeloma, and targeting this protein has emerged as a promising therapeutic approach in such cancers.
The anti-MUC1 antibody MAb-AR20.5, rather than acting directly on MUC1-expressing cells and causing their death, was shown to induce strong tumor-specific immune responses, functioning as an immunotherapy.
Indeed, MAb-AR20.5 has already shown promise in a Phase 1 trial in patients with MUC1-positive cancers, resulting in increased immune responses and favorable safety profiles.
Now, preclinical data in humanized pancreatic mouse models show this agent may be a promising treatment approach when used in combination with other immunotherapies. Combining MAb-AR20.5 with a checkpoint inhibitor and a TLR-3 agonist, both of which enhance the ability of T-cells to recognize and kill tumor cells, resulted in rejection or significant inhibition of tumor growth in mice injected with MUC1-positive pancreatic cell lines.
In addition, the MUC1-specific response was found to be long lasting, and when the researchers injected immune cells from mice previously treated with MAb-AR20.5 into mice that had never received the therapy, the injected immune cells could protect the transplanted mice from subsequent tumor challenge.
The findings support the increasing belief that combining two or more therapies yields better results in cancer treatment than the use of single therapies alone.
