Lent-On-Plus is the first-in-class platform favored for clinics where clinician decides when and how much turn on the potency of the therapy.
Lent-On-Plus is a synthetic system designed to fine-tuned control the expression of any relevan gene upon the addition of a drug in the absence of transactivators, which elevate this platform to the first and only transactivator-free system in the market and favored for clinics
Unlike the rest of TetOn system, Lent-On-Plus doesn’t requires transactivators. Transactivators are protein chimera formed by the fussion of the tetracycline represor (TetR) and the VP16 protein of the herpes simplex virus. VP16 is a transcription factor that is involved in the activation of the viral immediate-early genes. It has been shown that the presence of transactivators can bind to pseudoTetO sites and alter the normal expression pattern of the genes, causing loss of neurons and behavioral alterations, brain atrophy, emphysema and cardiomyopathies in mice. This constitute a hurdle for the translation to clinical applications.
In addition, Lent-On-Plus is extremely sensitive to its inducer, doxycycline (dox). Doxycycline is a well-tolerated antibiotic that can cross the brain barrier and can be orally administered. Lent-On-Plus works at a very sub-therapeutical dose as antibiotic, minimizing potential bacterial resistant risk.
Lent-On-Plus: a versatile and safe system for boosting immunotherapy
Lent-On-Plus for solid tumors
Conventional CAR-T cells has not provided relevant clinical effect and new generation of CAR-T cells, called TRUCKs has been developed to increase the potency by now expressiong a booster (normally cytokines). This booster can be continuously expressed or depend on the activation state of the CAR-T cells (endogenous control), and this superior potency also can lead to higher toxicities.
Lent-On-Plus is an ideal platform for controlling clinically relevant molecules to generate inducible TRUCKs (iTRUCKs) in a exogenously controlled- manner.
LOP-IL-18 is a therapeutical lentiviral vector that express interleukine-18 (IL-18) under the control of doxycycline for targeting solid tumors and hard-to-treat lymphomas.
LACK OF EFFICACY
50% of CAR-T treated patients with leukemias and lymphomas relapsed in few years. There is no effective CAR-T therapy for solid tumors.
IL-18 is a powerful cytokine and master regulator of the immune system, that triggers IFN-g and can transform «cold tumors» (with no immune infiltration) to «hot-tumors», easily to attack