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High Throughput Isolation of Antigen Specific T-cells for Cancer Therapy (NIH Technology Transfer)

Description:

 

The adoptive transfer of autologous tumor reactive T lymphocytes (T cells) can mediate significant tumor regression and long term cures in patients with refractory metastatic cancer. Despite these important clinical findings, adoptive cell transfer has not become widely available for patient treatment. Obtaining tumor infiltrating lymphocytes (TIL), T cells associated with a tumor that can exhibit high tumor reactivity, usually requires invasive surgery, which can lead to post-operative complications and is not always possible for all patients depending upon the location of their tumors. A significant obstacle in extending this promising therapy to a broader range of cancer patients has been the availability of highly efficient in vitro methods to rapidly isolate and expand tumor reactive T cells from peripheral blood for therapeutic use. Due to the low frequency of these T cells in the peripheral blood of cancer patients, isolation of these cells has traditionally been a difficult and laborious process requiring prolonged culture times and large amounts of reagents and equipment. Furthermore, the T cells typically generated during this protracted in vitro process develop unfavorable traits making them unsuitable for cancer therapy.

To overcome this significant challenge, intramural NIH investigators have invented a novel high throughput in vitro platform using quantitative RT-PCR (qPCR) as a functional screen to rapidly detect and isolate a variety of low frequency tumor reactive T cell clones from the peripheral blood of cancer patients (U.S. Patent Application No. 61/027,623). This novel technology has allowed the investigators to isolate and expand unique human T cells under GMP conditions that otherwise would not have been feasible. The utility of these inventions has been demonstrated by their application in isolating rare T cells and expanding them for human cancer therapy in an NCI sponsored clinical trial (NCI 08-C-0104).

This invention is the subject of U.S. Patent Application Number 12/866,919 and foreign counterparts in Europe and Australia(HHS Reference Number E-003-2008/0).

ProjectGoals:

The ultimate goal of this solicitation is to further refine and develop this novel T cell isolation platform into a standardizedmanufacturing operating procedure that could be commercialized for public and private use. The development of this technology would help overcome the fundamental obstacle of isolating highly tumor reactive T cells that circulate at low frequencies in the human body, which currently has prohibited the widespread use of adoptive T cell therapies. A current approach to obtain these low frequency tumor reactive T cells, such as TIL, from cancer patients is to use invasive surgical procedures to resect tumor and isolate TIL from the resected tumor. However, some tumors cannot be resected without risking patient mortality. The development of this current technology would provide patients with unresectable tumors another option for isolation of therapeutic T cells. If successful, this technology could potentially become the standard for tumor reactive T cell isolation and eliminate the need for the invasive surgical approach. The second long term goal of this solicitation is the development of novel applications for this T cell isolation platform, such as extending its applicability to other cancers and other disease indications. The awardee may have an opportunity to engage in collaborative research with NCI’s researchers and benefit from current expertise in the field for preclinical development and the clinical application of the technology.

This is an NIH TT (Technology Transfer) contract Topic from the NCI. This is a new program whereby inventions from the NCI Intramural Research Program (Center for Cancer Research, CCR) are licensed to qualified small businesses with the intent that those businesses develop these inventions into commercial products that benefit the public. The contractor funded under this contract Topic shall work closely with the NCI CCR inventor of this technology, who will provide patient samples, necessary assay equipment, as well as other reagents as needed. The inventor will provide assistance in a collaborative manner with reagents and discussions during the entire award period. Between the time this contract topic is published and the time an offeror submits a contract proposal for this Topic, no contact will be allowed between the offeror and the NCI CCR inventor. However, a pre-submission public briefing and/or webinar will be given by NCI staff to explain in greater detail the technical and licensing aspects of this program (for further information, see http://sbir.cancer.gov/news/upcoming/). In addition, a list of relevant technical, invention, and licensing-related questions and answers (including those from the public briefing) will be posted, maintained, and updated online (http://sbir.cancer.gov/news/upcoming/) during this time period.

The awarded contractor will automatically be granted a royalty-free, non-exclusive license to use NIH-owned and patented background inventions only within the scope and term of the award. However, an SBIR offeror or SBIR contractor mustnegotiate an exclusive or non-exclusive commercialization license to make, use, and sell products or services incorporating the NIH background invention. An SBIR contract proposal will be accepted as an application for a commercialization license to such background inventions. Under the NCI NIH TT program, the SBIR contract award process will be conducted in parallel with, but distinct from, the review of any applications for a commercialization license.

Model license agreements are available at http://www.ott.nih.gov/forms_model_agreements/forms_model_agreements.aspx#LAP. Certain terms of the model license agreement are subject to negotiation. Please contact the designated NIH Licensing and Patenting Manager(Samuel Bish, Ph.D., 301-435-5282, bishse@mail.nih.gov) with further questions.

Licensingprocedures will comply with Federal patent licensing regulations as provided in 37 CFR part 404. A further description of the NIH licensing process is available at http://www.ott.nih.gov/licensing_royalties/intra_techlic.aspx. NIH will notify an SBIR offeror or SBIR contractor who has submitted an application for an exclusive commercialization license if another application for an exclusive license to the background invention is received at any time before such a license is granted.

Any invention developed by the contractor during the course of the NIH TT contract period of performance will be ownedby the contractor subject to the terms of Section 8.5.

PhaseI Activitiesand Expected Deliverables:

Platform Development:

·       Develop protocol for T cell stimulation and growth in 384 well plate format to increase current throughput.

·       Develop protocol for RNA isolation in 384 well format to increase current throughput.

·       Develop 384 well multiplex qPCR assay for cytokine profiling.

·       Apply automated liquid handling technology to facilitate high throughput screening.

·       Apply automated liquid handling technology to facilitate T cell cloning.

Phase II Activities and Expected Deliverables:

A PhaseII proposal will typically/generally only be invited by NCI if the Phase I contractor has been granted a commercialization license via the process described above.

Development of novel application:

·       Epitope Discovery: Develop a novel high-throughput methodology to rapidly screen a peptide library of predicted peptides from putative antigen targets by analyzing their ability to stimulate human leukocyte antigen (HLA) matched human peripheral blood lymphocytes (PBLs).

·       Utilize current platform to identify functional gene expression signatures for unique T cell populations.

·       Isolation of novel T cell populations for human cancer therapy clinical trials.

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