Modular Inducible Cancer Immunotherapeutics (MICI)

At the center of our MICI platform are autologous dendritic cells (DC) that have been transduced ex vivo with our RheoSwitch Therapeutic System® (RTS) and one or more genes-of-interest (GOI). The GOI is under the regulated control of the RTS using dosing of our activator ligand. This DC-RTS-GOI combination cell therapy is then injected directly into a selected solid tumor in situ. The encoded GOI is subsequently activated and regulated by the timing and dosing levels of the activator ligand. This first-in-class cancer immunotherapeutic approach is currently being evaluated in an open-label Phase 1b clinical trial. Previously, our lead activator ligand was the subject of a Phase 1a randomized, double-blinded, placebo-controlled, dose-escalation, safety study in 65 normal healthy male and female volunteers. Results demonstrated this lead activator was well tolerated at all dose levels studied, achieved steady-state pharmacokinetics, attained high serum bioavailability levels, and yielded a metabolic half-life consistent with once-a-day dosing.

Intrexon is using its modular UltraVector® system to rapidly design, assemble, and evaluate potent cytokines as either monotherapies or in combination with pre-loaded antigens and other adjuvants. This involves the progressive screening of over 100 different DC-RTS-GOI candidate combinations against different tumor types and stages. The integrated "dials" at right help illustrate these combinations and the opportunity to empirically derive the most promising lead candidates in a relatively short time course.

Key features of our MICI (DC-RTS-GOI) platform and approach include:

INDUCIBLE
  • intratumoral (in situ) induction of DC-RTS-GOI using a small molecule activator
  • proportional expression of GOI using corresponding dosing amounts of the activator
  • prospective safety and efficacy advantages using dosing levels and OFF expression
SPECIFIC
  • in situ antigen processing/presentation
  • relevant lymph drainage routes (post-intratumoral injection)
  • acquisition of unique antigen mix using same therapy and procedure (intrinsically personalized)
MODULAR
  • UltraVector®-enabled architecture, with reuse of proven components
  • rational design, assembly, and optimization to derive new candidates
  • rapid combinatorial screening and evaluation
SCALABLE
  • centralized DC processing
  • same leukapheresis and centralized DC processing regardless of RTS-GOI
  • distributed leukapheresis and DC/activator dosing