The Field: The most effective treatment for metastatic melanoma is Tumor Infiltrating Lymphocyte (TIL) therapy, in which TILs are obtained from a patient's tumor fragments, grown to an immense quantity in vitro, and infused back into the patient (1-4). The Problem: Despite its ability to provide complete remission, the process of growing a therapeutic cell dose is so inefficient and complicated that TIL therapy cannot escape the Valley of Death. The Proposed Solution: Under prior Phase II SBIR GM058978, we created a paradigm shift in cell culture device technology that has been extensively studied for TIL production. The results demonstrate a greatly simplified process can be created that will allow TIL therapy to move beyond the Valley of Death and onto a commercial path. The key is to allow TILs to reside on a highly gas permeable, liquid impermeable membrane submerged under an unconventionally high level of medium. We call this approach "G-Rex". With TILs in this position, they have access to oxygen and nutrients on demand without need of expensive and complicated ancillary equipment. Using this device configuration, we intend to reduce the TIL production process from up to 60 conventional devices and 30L of medium to just 2 G-Rex devices and as little as 4L to 5L of medium. Many other production advantages are inherent to this level of process simplification. As a result of this program, the potential for profit by applying TIL therapy will exist and commercial entities will be spurred to capitalize on the powerful outcomes of TIL therapy. The Investigation: Our investigation will provide the most efficient TIL production possible by optimizing G- Rex Protocols and devices:
Aim 1 : Determine the optimal TIL surface density that minimizes the duration of TIL Rapid Expansion Process Aim 2: Determine the optimal height of the G-Rex that will minimize the feeding frequency during the TIL Rapid Expansion Process (REP).
Aim 3 : Define the variance of gas permeable membrane thickness allowed in full scale G-Rex devices.
Aim 4 : Full scale validation of optimized G-Rex TIL culture S.O.P.s and G-Rex device specifications. The status of TIL therapy upon completion of this program: Separate from this optimization program, clinical application of G-Rex in the non-optimized state is already occurring. Upon completion of this investigation, the optimized G-Rex will transition into a multi-center comparability study followed by a randomized study, FDA approval, and commercially available TIL therapy.

Public Health Relevance

The most effective treatment for metastatic melanoma is Tumor Infiltrating Lymphocyte Therapy (TIL therapy), in which a patient's TILs are obtained from tumor fragments, grown to an immense quantity in vitro, and infused back into the patient. Despite its ability to provide complete remission, the complicated process of growing a therapeutic cell dose is driving TIL therapy into the Valley of Death. Under prior Phase II SBIR GM058978-02, we created a paradigm shift in cell culture device technology that will create the efficiency needed to spur commercialization of TIL therapy. The optimization activity of this program will move TIL therapy past the Valley of Death and onto a commercial path.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Small Business Innovation Research (SBIR) Cooperative Agreements - Phase II (U44)
Project #
3U44CA165607-06S1
Application #
8926581
Study Section
Special Emphasis Panel (ZCA1-SRLB-X (O2))
Program Officer
Weber, Patricia A
Project Start
2011-09-26
Project End
2015-08-31
Budget Start
2013-09-18
Budget End
2015-08-31
Support Year
6
Fiscal Year
2014
Total Cost
$200,624
Indirect Cost
Name
Wilson Wolf Manufacturing Corporation
Department
Type
DUNS #
170969237
City
New Brighton
State
MN
Country
United States
Zip Code
55112