WATERTOWN, Mass.—Selecta Biosciences, Inc., a clinical-stage biopharmaceutical company focused on unlocking the full potential of biologic therapies by avoiding unwanted immune responses, announced today that Proceedings of the National Academies of Sciences (PNAS) has published a paper co-authored by the company with researchers from the National Cancer Institute (NCI), part of the National Institutes of Health. The paper, entitled Tolerogenic nanoparticles restore the anti-tumor activity of recombinant immunotoxins by mitigating immunogenicity, focuses on work conducted by Selecta and Dr. Ira Pastan’s lab at NCI. Dr. Pastan is Senior Investigator, Head, Molecular Biology Section, at NCI’s Center for Cancer Research and a Fellow of the National Academy of Sciences.
“The efficacy of protein-based drugs, including promising immunotoxins such as LMB-100, can be limited by the formation of anti-drug antibodies (ADAs),” said Takashi Kei Kishimoto, Ph.D., Chief Scientific Officer of Selecta and a co-author of the publication. “Led by researchers at NCI, this preclinical work highlighted the ability of SVP-Rapamycin to mitigate immunogenicity to LMB-100, which is a critical step toward delivering on the full potential of this very promising class of drugs in the field of oncology. We look forward to working with NCI researchers to bring this combination therapy, known as SEL-403, into the clinic later this quarter.”
Selecta’s SEL-403 product candidate consists of SVP-Rapamycin in combination with LMB-100. SVP-Rapamycin is Selecta’s proprietary, clinical-stage ADA prevention and immune tolerance technology. LMB-100 was in-licensed by Selecta from NCI. It is a recombinant immunotoxin that targets mesothelin, a protein expressed in nearly all mesotheliomas, pancreatic adenocarcinomas and a high percentage of other malignancies, including lung, breast and ovarian cancers.
The FDA recently accepted an investigational new drug application for a combination therapy consisting of Selecta’s SVP-Rapamycin and LMB-100 for the treatment of patients with malignant pleural or peritoneal mesothelioma. The use of SVP is also being explored in the development of vaccines and treatments for allergies and autoimmune diseases.
In the PNAS publication, the authors described preclinical work in which SVP-Rapamycin mitigated the formation of inhibitory ADAs to LMB-100 in both naïve mice and mice pre-exposed to LMB-100, resulting in restoration of LMB-100’s anti-tumor activity. The authors note that this strategy for mitigating immunogenicity is indicative of a novel approach to unlock the full potential of recombinant immunotoxin therapy for solid tumors and that the results may have implications for other highly foreign, lifesaving therapeutic proteins. An abstract of this publication can be accessed at http://www.pnas.org/content/early/2018/01/03/1717063115.abstract.
Selecta’s SVP-Rapamycin platform is also discussed in the January 2018 edition of Scientific American. The article can be found at https://www.scientificamerican.com/article/why-our-own-immune-systems-attack-our-best-drugs-mdash-and-how-to-stop-it/.