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Advanced Manufacturing to Speed Availability of Emerging Autologous Cell-Based Therapies


Fast-Track proposals will be accepted. Direct-to-Phase II proposals will NOT be accepted. Number of anticipated awards: 2-4 Budget (total costs, per award): Phase I: up to $400,000 for up to 9 months Phase II: up to $2,000,000 for up to 2 years PROPOSALS THAT EXCEED THE BUDGET OR PROJECT DURATION LISTED ABOVE MAY NOT BE FUNDED. Summary Current manufacturing processes for autologous cell-based cancer therapies are complex, slow, labor intensive, and expensive. These involve highly personalized methods requiring leukapheresis followed by ex vivo manipulation of cells before a therapy can be administered to the patient. While autologous cell-based therapies offer great promise for cancer treatment, there is growing concern that current manufacturing methods are unable to support the delivery of these treatments to the large numbers of patients eligible to receive them. In particular, the cell processing period between cell isolation and therapeutic administration, referred to as ‘vein-to-vein’ time, currently takes from 3-8 weeks. Using current methods, medical center laboratories that provide cell-based therapy often have the capacity to treat only 2-8 patients per month, which is insufficient to meet the high demand of clinical trials. Moreover, given that cell-based cancer therapy is still in its nascent stages, higher patient throughput is likely to accelerate the iterative bench-to-bedside-to-bench research that will be needed to improve and mature this treatment modality. Advanced manufacturing approaches that can process multiple cell therapies for several patients in parallel could substantially improve the availability of emerging autologous cell-based therapies. Achieving this complex, multi-step, parallel processing is likely to require automated systems that can continuously control and monitor critical quality attributes of the engineered cells. Such systems must also be capable of optimizing and maintaining the desired physiological and immunological status of the expanded cells in a multiplexed fashion, while overcoming issues of cell senescence and exhaustion. A further challenge may involve miniaturization of cell culturing processes to achieve greater efficiency and higher throughput as compared to current approaches. It is expected that advanced manufacturing technologies will decrease both the cost and time required to deliver emerging autologous cell-based therapies to a greater number of patients, including those patients with rapidly progressing disease for whom autologous therapies may not currently be feasible. Project Goals The overall goal of this solicitation is to stimulate the development of advanced manufacturing technologies that substantially improve the speed and cost of producing autologous cell-based therapies. Technical solutions are expected to involve parallel processing (i.e., multiplexing) of individual cell-based therapies, although other approaches are encouraged. New technologies must produce cell-based products of equal or superior quality as compared to current manufacturing methods. In addition, the NCI encourages system design features that enable rapid and iterative customization to support bench-to- bedside-to-bench research. For example, technologies may involve a modular engineering approach in which the system can be readily adapted as the critical quality attributes of cell-based products are refined over time based on new clinical research. Proposals submitted under this topic must involve a collaboration between technology developers and clinical researchers with experience developing and treating patients with autologous cell-based cancer therapies. Phase I projects will be expected to involve feasibility testing of the proposed advanced manufacturing technology. A key activity during the Phase I project is to benchmark the novel advanced manufacturing approach against the current manufacturing method for a specific autologous cell-based product. More specifically, the research plan must include validating the proposed novel manufacturing approach against a process that has been used to produce product for clinical trials by demonstrating comparability of products with respect to specific critical quality attributes. Phase II projects will be expected to conduct full-scale parallel processing to demonstrate a substantial increase in the speed and cost of producing autologous cell-based therapies. It is anticipated that most offerors will propose to study T-cell-based immunotherapy products, although other cell types are also encouraged (e.g., NK cells). Advanced manufacturing approaches may involve genetic engineering and optimization as appropriate for the cell-based therapy product, but the primary goal is to achieve substantial cost and throughput improvements for the overall vein-to-vein process. Projects proposing to use allogeneic cell-based therapies for technology validation will not be considered responsive under this solicitation. Phase I Activities and Deliverables: • Provide proof of collaboration with an engineer(s), immunologist(s) and clinician(s) that has experience developing high throughput systems and/or treating patients with autologous cell-based cancer therapies; • Establish assays and/or metrics, especially functional comparability and quality attributes, for benchmarking the approach against current manufacturing methods; • Establish defined specifications to enable integrated high throughput parallel manufacturing at faster speed and lower cost than current manufacturing methods; • Develop an early prototype device or technology for integrated high throughput autologous-cell manufacturing that include specifications designed to substantially reducing the speed, as well as any cost savings based on the new manufacturing approach; • Demonstrate the suitability of the approach to manufacture a minimum of two cell products in parallel • Demonstrate pilot-scale beta-testing of the approach comparing it against appropriate benchmarking technology • Demonstrate the immunological functionality of the cells based on the previously identified functional comparability assays and/or metrics, and compare cell function to appropriate benchmarking technology; • Establish cell culturing technology compatible with high throughput production and technology to monitor the cells Phase II Activities and Deliverables: • Develop an at-scale prototype of the approach with detailed specifications for hardware/software that supports the manufacturing of multiple cell products simultaneously • Generate scientific data demonstrating the proposed scalability (e.g. scale-out, point-of-use) of the technology and demonstrate cost and time improvements over current clinical standard • Demonstrate comparable quality between the current manufacturing standard and cell-products manufactured at scale with the proposed approach
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