SVP-Rapamycin, an immunotherapy developed by Selecta Biosciences, can strengthen the effective of an anti-mesothelioma therapy, according to preclinical data recently presented at the Immunogenicity and Bioassay Summit 2016 in Baltimore. These findings may lead to a new therapy approach for certain types of cancer, including mesothelioma.
The studies were carried out under a Cooperative Research and Development Agreement (CRADA) between Selecta Biosciences and researchers with the Center for Cancer Research at the National Cancer Institute (NCI).
The first presentation, “Strategies to Reduce Immune Response to Immunotoxins,” was made by Ira Pastan, MD, while Ronit Mazor, PhD, delivered the second, “Induction of Tolerance to Immunotoxins Using Nanoparticle Delivery of Rapamycin.” Mazor also presented the poster, “Nanoparticle-Encapsulated Rapamycin Prevents Primary and Secondary Immune Responses in Murine Models.”
The studies evaluated the effectiveness of SVP-Rapamycin given in combination with an experimental anti-cancer drug, LMB-100. Developed in Pastan’s lab, LMB-100 is an antibody fragment against mesothelin (a protein highly expressed in mesothelioma cells, but rare in healthy cells) linked to an engineered portion of Pseudomonas’ exotoxin A. After binding to mesothelin, LMB-100 is designed to kill cancer cells.
LMB-100 was also designed to reduce the side effects of a similar drug (SPP1) seen in most patients with chemotherapy-refractory mesothelioma. The strong side effects limited use of SPP1, but those patients who tolerated more than one treatment cycle showed marked antitumor activity. LMB-100 is currently undergoing Phase 1 clinical testing at the NIH Clinical Center in patients with mesothelioma (NCT02798536) and pancreatic cancer.
In mice, adding SVP-Rapamycin to LMB-100 enhanced the drug’s effectiveness by preventing immune system side effects, allowing for at least four treatment cycles. In a tumor model, administration of SVP-Rapamycin also restored LMB-100’s ability to control tumor growth.
“These pre-clinical proof of concept data clearly demonstrate the potential benefit of co-administrating LMB-100 and SVP-Rapamycin, two products currently used in clinical trials,” Peter Keller, MSc, chief business officer at Selecta, said in a news release. “The program is part of our objective to extend our clinical pipeline by applying our SVP technology platform to oncology treatments. In oncology, the effectiveness of many therapies could be enhanced by antigen-specific mitigation of undesired immune responses.”
Researchers believe that SVP-Rapamycin can also be combined with other biologic drugs to make those treatments more effective and safe for greater numbers of patients.
One example is Selecta’s lead product candidate, SEL-212, that brings together SVP-Rapamycin and an enzyme called pegsiticase, and is currently being tested in a Phase 2 trial as a therapy against chronic refractory and tophaceous gout.