CELL AND GENE THERAPY
Mnemo Therapeutics | January 24, 2022
The journal Nature Medicine recently published a study in which researchers developed a novel receptor to enhance recognition of tumors by engineered T cells, addressing an underlying cause for relapsed tumors in patients after chimeric antigen receptor therapy. The study demonstrates high antigen sensitivity of HLA-independent T-cell receptors, created by editing the TCR Alpha Constant chain locus in human peripheralbio blood Tcells.
Low antigen expression
One major limitation of CARs is antigen escape, when a tumor no longer expresses the antigen detectable by the CARs or expresses them at a very low level; CARs with heightened sensitivity to low-expression level antigens boosts the efficacy of otherwise promising T-cell therapies.
In the study, conducted by researchers at New York's Memorial Sloan Kettering Cancer Center, researchers produced HIT T-cells and analyzed them in animal models
HIT T-cells were engineered from human peripheral blood T-cells by inserting variable region genes in the TRAC locus, endowing the cell with a single specificity for a target antigen such as CD19. Notably, this sensitivity was shown to be higher than traditional CARs for low levels of antigen expression resulting in superior cytotoxicity and cytokine secretion.
HIT Tcells outperformed traditional CAR T-cells in vivo in mouse models of B cell leukemia and acute myeloid leukemia, without costimulation. Coexpression of HIT with CD80 and 4-1BBL further augmented therapeutic activity and mouse survival.
HIT T-cells are a promising therapy for targeting cancer cell surface antigens with low abundance due to their sensitivity and persistence.
The team responsible for this important work includes MSKCC researcher and Mnemo Therapeutics scientific cofounder Michel Sadelain, M.D., Ph.D., MSKCC researcher and Mnemo scientific advisor Isabelle Rivière, Ph.D., as well as Justin Eyquem, Ph.D., University of California San Franciso and Mnemo scientific cofounder.
Mnemo's EnfiniT Platform
These findings support Mnemo's EnfiniT platform as the next-generation toolkit for CAR-T immunotherapies, which are founded on decades of breakthrough research from Institut Curie and MSKCC, and supported with best-in-class T-cell manufacturing. The EnfiniT platform brings together a suite of technologies to address the key challenges associated with CAR T therapies by both identifying a new class of antigens with greater tumor specificity and applying a range of technologies to significantly improve T-cell memory, persistence and sensitivity. The goal is to dramatically improve the body's ability to fight and overcome disease.
About Mnemo Therapeutics
Mnemo Therapeutics is a biotechnology company focused on the development of powerful new cell therapies. With its EnfiniT platform, Mnemo applies a novel, integrated approach to T-cell therapy to transform the body's immune response to overcome disease. Mnemo is headquartered in Paris with an office in New York City, and it maintains state of the art laboratories in Paris, New York, and Princeton, New Jersey. The company leverages an international talent pool and global resources in its quest to create accessible cures for all patients in need.
Roivant | May 13, 2020
Roivant Sciences today announced several updates for its adaptive, randomized, double-blind, placebo-controlled, multi-center pivotal BREATHE trial evaluating the impact of intravenous (IV) treatment with gimsilumab on mortality in COVID-19 patients with lung injury or ARDS.The independent Data Monitoring Committee (DMC) for BREATHE unanimously recommended that the trial continue after a pre-specified safety assessment evaluating data from the first 10% of randomized subjects after six days of follow-up.In addition, Roivant recently amended the protocol to permit the use of investigational antivirals (e.g. remdesivir) during the study, as well as treatment with convalescent plasma prior to enrollment. 56 patients have been enrolled in the study to date, and a total of 7 sites have been initiated in New York, Philadelphia, Detroit, New Orleans, Dallas, and Atlanta."We are pleased with the rapid progress we have made to date on the BREATHE program. The adjustments to our protocol reflect our desire to ensure patients receive the best possible treatment. We believe gimsilumab may prove to be complementary with antivirals and convalescent plasma and anticipate providing a definitive answer to the question of whether an anti-GM-CSF antibody can provide benefit to COVID-19 patients," said Simon Lowry, MD, the program's lead.
INOVIO | September 28, 2020
INOVIO (NASDAQ:INO), a biotechnology company focused on bringing to market precisely designed DNA medicines to treat and protect people from infectious diseases and cancer, announced that the U.S. Food and Drug Administration (FDA) has notified the company it has additional questions about the company's planned Phase 2/3 trial of its COVID-19 vaccine candidate INO-4800, including its CELLECTRA® 2000 delivery device to be used in the trial. Until the FDA's questions have been satisfactorily addressed, INOVIO's Investigational New Drug Application (IND) for the Phase 2/3 trial is on partial clinical hold. The company is actively working to address the FDA's questions and plans to respond in October, after which the FDA will have up to 30 days to notify INOVIO of its decision as to whether the trial may proceed. This partial clinical hold is not due to the occurrence of any adverse events related to INOVIO's ongoing expanded Phase 1 study of INO-4800, the conduct of which may continue and is not impacted by the FDA's notification. In addition, this partial clinical hold does not impact the advancement of INOVIO's other product candidates in development. INOVIO and its partners are continuing to prepare for a planned Phase 2/3 trial of INO-4800, following resolution of the FDA's partial clinical hold and subject to the receipt of external funding to conduct the trial.