On November 8, 2019 Rubius Therapeutics, Inc. (Nasdaq: RUBY), a clinical-stage biopharmaceutical company that is genetically engineering red blood cells to create an entirely new class of cellular medicines, reported that the Company presented preclinical data supporting its lead artificial antigen presenting cell program, RTX-321, for the potential treatment of HPV 16-positive tumors at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 34th Annual Meeting (Press release, Rubius Therapeutics, NOV 8, 2019, View Source [SID1234550760]). Last month at the AACR (Free AACR Whitepaper)-NCI-EORTC International Conference on Molecular Targets and Cancer, Rubius Therapeutics presented data demonstrating that its Red Cell Therapeutics can be engineered to create a loadable system for personal neoantigens, unlocking a potential new use of our RED PLATFORM.
Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:
Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing
Schedule Your 30 min Free Demo!
"Current cell therapy approaches are limited by a number of challenges – they require harvesting and engineering a patient’s own T cells, undergo a lengthy manufacturing process, are limited in the number of targets that can be pursued, and, once administered to patients, can elicit unpredictable immune responses, including severe side effects. Today at SITC (Free SITC Whitepaper), we presented additional preclinical proof of concept data demonstrating that Rubius Therapeutics can engineer allogeneic artificial antigen presenting cells against a tumor-associated antigen that significantly expand antigen-specific T cells and nearly eliminates lung metastases in a melanoma mouse model with minimal, reversible toxicity," said Pablo J. Cagnoni, M.D., chief executive officer of Rubius Therapeutics. "Separately, current personalized neoantigen approaches are promising, but do not adequately stimulate and expand the right subset of T cells to the levels required to achieve robust efficacy. Last month at AACR (Free AACR Whitepaper)-NCI-EORTC, Rubius Therapeutics presented data showing that we can engineer our red cells to create a loadable system for personal neoantigens and dramatically expand primary T cells to induce an immune response, unlocking a potential new use of our RED PLATFORM."
Data Summaries
Red Cell Therapeutic Artificial Antigen Presenting Cells (aAPCs) at SITC (Free SITC Whitepaper)
(P233) RTX-321, an Allogeneic Artificial Antigen Presenting Red Cell Therapeutic, Expressing MHC I-Peptide, 4-1BBL and IL-12, Promotes Antigen-Specific T Cell Expansion and Anti-Tumor Activity in HPV16+ Tumors
Allogeneic Red Cell Therapeutic artificial antigen presenting cells (RTX-aAPCs) are engineered to induce a tumor-specific response by expanding antigen-specific T cells.
As preclinical proof of concept, mouse red cells were chemically engineered with hundreds of thousands of copies of the major histocompatibility complex (MHC) I loaded with the gp100 peptide, a melanoma antigen, 4-1BBL and IL-12 on the cell surface and were tested in a B16-F10 melanoma mouse model.
These cells (mRBC-gp100-4-1BBL-IL-12 ) nearly eliminated lung metastases at the highest dose levels.
mRBC-gp100-4-1BBL-IL-12 promoted gp100-specific T cell expansion in the circulation, secondary lymphoid organs and lungs.
RTX-aAPC was engineered with a cytomegalovirus (CMV) antigen, 4-1BBL and IL-12 and expanded CMV-specific T cells from healthy donor peripheral blood mononuclear cells (PBMCs).
RTX-321 (HPV+) was engineered to express an HPV peptide antigen bound to MHC I, 4-1BBL and IL-12 on the cell surface to mimic human T cell-APC interactions.
Expression of IL-12 as signal 3 on an aAPC resulted in more robust antigen-specific T cell expansion, memory formation and cytotoxicity against tumor cells when compared to IL-7 or IL-15, leading the Company to select IL-12 as signal 3 for RTX-321.
RTX-321 is selectively directed against an HPV dominant epitope and promoted T cell receptor (TCRs), 4-1BB and IL-12 receptor signaling in engineered cell lines.
RTX-321 expanded HPV-specific TCR-transduced primary human T cells.
RTX-321 is currently in IND-enabling studies.
Loadable Red Cell Therapeutic Artificial Antigen Presenting Cells for Neoantigens at AACR (Free AACR Whitepaper)-NCI-EORTC
(B062) Enabling the Rapid Generation of Allogeneic Artificial Antigen Presenting Cell (aAPC) Red Cell Therapeutics with a Loadable MHC System
Allogeneic Red Cell Therapeutic artificial antigen presenting cells (RTX-aAPCs) are engineered to induce an tumor-specific response by expanding antigen-specific T cells.
A loadable MHC system was engineered to enable the rapid generation of aAPCs targeting personal neoantigens.
Antigenic peptides can be loaded onto empty MHC constructs, which can be stably expressed at high levels.
RTX-aAPCs with peptide-loaded MHC constructs functionally engaged TCRs and achieved robust expansion of primary CMV-specific T cells in healthy donor PBMCs with prior exposure to CMV.
Rubius Therapeutics’ loadable aAPC system has the potential to generate aAPCs containing multiple neoantigens in a single therapeutic.
Further development of a loadable aAPC system may enable effective personalized neoantigen therapies.