BALTIMORE—Lentiviral vector developer and manufacturer Lentigen Corp. recently announced the signing of a collaborative research agreement with the University of Pennsylvania, under which Lentigen will work with Dr. James Riley of the university's medical school in developing novel cancer therapies. Financial terms were not disclosed, but Lentigen noted that it will be granted exclusive rights to commercialize products resulting from the research.
The work focuses on co-stimulatory pathways that control human T cell activation and differentiation, with one of the major areas of interest being signal transduction pathways initiated by members of the CD28 family—specifically CD28, ICOS, CTLA-4, PD-1 and BTLA. Although they have structural similarity, these receptors have distinct roles in modulating the immune system. The initial work of the collaboration aims to use the knowledge of T cell signaling pathways to design novel cancer therapeutics, primarily for treatment of B cell malignancies, such as leukemia and lymphoma, and ovarian or peritoneal cancer. However, the potential drug discovery targets could extend to non-oncology indications in the future.
"Immunotherapy for cancer is becoming a commonplace second-line, and in certain cases, first-line adjunct therapy," notes Dr. Carl H. June, director of translational research at the Abramson Cancer Center of the University of Pennsylvania and a professor in the Department of Pathology and Laboratory Medicine at U Penn, where Riley's laboratory is located. "The work developed by Penn in collaboration with Lentigen is a cellular-based immunotherapy and will add to the immunotherapy options available to patients with relapsed or refractory cancer. Cellular-based therapies offer the promise of durability and less toxicity than presently available cancer treatments."
Partnering with Lentigen was important, June says, because advancements in their products now offer researchers the necessary flexibility for preclinical- to clinical-grade lentiviral vectors. "This allows Penn to utilize their vectors for preclinical research," he explains, "and when the research is ready for clinical development, Lentigen can rapidly transition the vector production to clinical-grade to enable its application."
June adds that one of the critical challenges of the research will be to identify tumor antigens that are not expressed in healthy tissue, in order to avoid toxicity. A key part of this work of finding efficacious and non-toxic therapies relies on the generation of universal tumor-specific T cell receptors, otherwise known as chimeric immune receptors (CIRs) or T-bodies. By helping researchers find "universal receptors" that can be used across all patients with common tumor antigens, this research can "open the door for [a CIR] approach against a variety of tumor antigens, allowing the field to determine optimal antigens for each cancer," June says.