A critical aspect of validating the therapeutic activity of a new agent is to be able to directly correlate the expression of the test agent with the biological effect. In the matter of RNA interference therapeutics, quantification of intracellular expression and/or localization of the RNAi molecules has been problematic due to the small size of the RNAi.
The specific aims i n Core C will be:
Aim 1 : To oversee the production methods and acquisition of cGMP reagents necessary for the phase 1 trial: ITI has established an agreement with Xcyte Therapies Inc. for the use of their proprietary cGMP-quality anti-CD3/anti-CD28 coated beads. These will be used for T cell expansion. All technology and procedures necessary for the expansion of these cells will be the responsibility of ITI and Core C will interact closely with Core C for the actual transduction and expansion of these cells.
Aim 2 : To perform quantitative measurements of RNAi necessary for the evaluation of lentivirus vectors developed in projects 1 and 2 and safety tested in Project 4: ITI has developed a proprietary technology called ProxiQuantTM that is able to measure small RNA molecules and which will be required for all pre-clinical and clinical assessment of vector induced RNAi expression efficiency. This is the only such technology forstandardization of transgene expression in this field.
Aim 3 : To execute the procedures for T cell transduction and expansion necessary for phase 1 clinical trials: The facilities of the CBG at BRICOH has considerable expertise in expansion of transduced T cells under cGMP conditions, and will be used for all production of the clinical grade products. The CBG has a BL-3 level areawithin the cGMP laboratories that will be used for these expansions. The clinical IND will cross reference the methods already approved by the FDA for ongoing T cell immunotherapy projects.
Aim 4 : To coordinate the completion of the IND application, to maintain and monitor operations according to cGMP regulations, and to interact with the FDA on behalf of the P.I. for regulatory matters: ITI has experience in FDA applications and study implementation and will be responsible for seeing that all target deadlines and regulatory requirements are properly observed. Thus, the core will serve as a valuable resource as a liaison with the FDA for issues related to the phase 1 trial.
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