Efficient Transduction and Gene Expression – Improving Clinical Trials
Developing modern cell therapies necessitates exact control of gene expression.
The SIRION technology platform offers versatile options to identify and optimize the best possible approach for your preclinical and therapeutic R&D.
LentiBOOST™ - improve transduction of hematopoietic cells
LentiBOOST™ is a highly effective, non-cytotoxic chemical lentiviral transduction enhancer for preclinical and clinical applications. As universal acting (receptor independent) adjuvant it can be applied to a wide range of clinically relevant cell types including CD34+ hematopoietic stem cells (HSCs), primary T cells and NK cells. These unique features make it a promising candidate to improve clinical transduction protocols for ex vivo gene therapies and CAR-T cell therapies.
Read about LentiBOOST™ in the news.
Available in two grades;
LentiBOOST™ pharma grade
for use in preclinical research and process development. Available for evaluation studies under MTA. Licensing options for Research Use, Development and Commercial Use are available.
Please inquire with firstname.lastname@example.org.
LentiBOOST™ GMP grade
for use in clinical stage protocols. Currently included in Phase III and I/II clinical trials in the US and in Europe. Licensing options for Commercial Use and Development are available.
Please inquire with email@example.com.
In the demonstration above, LentiBOOST™ increases transduction by a factor of 5.
Benefits for Drug Development at a glance
Improved lentiviral transduction efficiency, up to 90%.
⇒ Increased expression levels of therapeutic protein have a favorable effect on success rates of clinical trials.
Positive impact on cell proliferation for CD34+ and T cells.
⇒ Reduced cost of goods, optimized and stable transgenic cell manufacturing.
Increased vector copy numbers per cell.
⇒ Strong and durable therapeutic protein expression, in line with FDA/EMA criteria for ATMPs production.
Successful track record of integration into clinical trials (III and I/II) in the US and Europe.
⇒ Proven lack of cell toxicity and prior clinical applications expedite IND filing.
GMP grade batches available.
⇒ Direct integration into clinical programs possible.
LentiTHERAPY™ - cell specific transduction technology
LentiTherapy™ is designed to enable cell type specific transduction and improve standard transduction efficiencies. The system is a great candidate for clinical research applications because of its universal applicability and non-toxic chemistry. Proven effective in CD30 and EGFR positive cell types.
The LentiTherapy™ 3 hit strategy to target therapeutically relevant cell types
Step 1: Retargeting antibody fragments on the virus envelope. These single-chain antibody fragments have a high affinity and specificity to peripheral proteins of cell surfaces, allowing targeted precision of viral transduction.
Step 2: LentiBOOST™ transduction enhancer increases the permeability of cell membranes, allowing lentiviruses easy access. The chemical basis for LentiBOOST™ is non-toxic and is used as a standard component in pharmaceutical pill formulation. This unique transduction enhancer is especially potent when used on non-adherent cells such as B-cell and T-cell transduction.
Step 3: Spinoculation increases the number of virusparticles binding to the cellsthrough centrifugal inoculation, enhancing the effectivenessof LentiBOOST™ and the retargeted envelope even further.
Due to its non-toxicity, the process is well suited for basic research as well as early clinical applications. LentiTherapy™ achieves sufficient genetic modification at low MOIs (less or equal to 1).
The figures show transduction experiments in KARPAS-299, SUP-M2 and SUDHL-1 cell lines incubated at MOI 10 or with copGFP-coding lentiviral particles +/- a spinoculation protocol, LentiBOOST (TM) and retargeted scFv-CD30 VSV-G lentivirus.
LentiTherapy™ is effective independent of cell type. The steps of this system influence each other synergistically, as demonstrated in the figure above. The treatment is effective at different MOIs and ideal for treating otherwise hard to transduce,therapeutically relevant cell types.
The LentiBOOST™transduction enhancer has been reported by collaborators from the academic sciences at the NYU Langone Medical Center to increase T-cell transduction significantly.
SIRION Biotech is searching for collaboration partners to help actively develop the application of the LentiTherapy™ Systemin pre-clinical and early clinical stages.
Höfig et al.,Poloxamer synperonic F108improves cellular transduction with lentiviral vectors. J. Gene Med. 14:549-60 (2012)
Höfig et al.,Systematic improvement oflentivirus transduction protocols by antibodyfragments fused to VSV-G as envelope glycoprotein. J. Biomaterials(2014)
Contact us – discover how SIRION can excel to your therapeutic R&D.