Stephan Lab

Creating more effective methods to harness the antitumor activity of immune cells

PROJECT 1: Biomaterial-supported lymphocyte implants for the control of tumors

Sirkka B. Stephan, Alexandria M. Taber, Ilona Jileaeva, Ericka P. Pegues, Charles L. Sentman and Matthias T. Stephan. Biopolymer implants enhance the efficacy of adoptive T cell therapy. Nature Biotechnology. 33, 97-101 (2015).

http://www.nature.com/nbt/journal/v33/n1/full/nbt.3104.html

 

Smith TT, Moffett HF, Stephan SB, Opel CF, Dumigan AG, Jiang X, Pillarisetty VG, Pillai SPS, Wittrup KD, Stephan MT. Biopolymers codelivering engineered T cells and STING agonists can eliminate heterogeneous tumor. Journal of Clinical Investigation. 2017 Jun 1;127(6):2176-2191.

http://www.jci.org/articles/view/87624.html

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Cancer relapse after surgery represents a major clinical problem and is frequently the ultimate cause of death. Our group is developing bioactive polymer implants that can deliver, expand and disperse tumor-reactive T cells as a means to treat incompletely resected or inoperable tumors. These cell-containing scaffolds can be surgically implanted at tumor resection sites, or situated directly on tumors that cannot be removed safely by surgery.


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Once implanted at the tumor resection site, the scaffold acts as a reservoir, releasing anti-cancer immune cells as it slowly breaks down, much like dissolvable stitches. Already at their job site, those immune cells can immediately begin eliminating residual cancer cells that the surgeon couldn’t remove. The therapeutic cells can even chase down cancer cells that have begun to spread through lymph nodes to other parts of the body. This is a huge advantage since one of the greatest risks patients face is that their cancer will return after surgery, sparked by just a handful of stowaway cells. Another advantage is that researchers don’t need as many T cells for the scaffold as they do for systemically delivered T-cell therapy. Obviating the need to grow billions of cells in the lab saves time and money and allows researchers to use T cells that are more powerful cancer fighters because they haven’t undergone as much manipulation in the lab.

International Patent  WO 2014/110591 A1 "Compositions and methods for delivery of immune cells to treat un-resectable or non-resectable tumor cells and tumor relapse".  Publication date: Jul 17, 2014. Inventor: Matthias Stephan

 

PROJECT 2: In situ programing of leukemia-specific CAR T cells using synthetic nanocarriers

Tyrel T. Smith, Sirkka B. Stephan, Howell F. Moffett, Laura E. McKnight, Weihang Ji, Diana Reiman, Emmy Bonagofski, Martin E. Wohlfahrt, Smitha P. S. Pillai & Matthias T. Stephan. In situ programming of leukaemia-specific T cells using synthetic DNA nanocarriers. Nature Nanotechnology. 2017 Aug: 813-820.

http://www.nature.com/nnano/journal/v12/n8/full/nnano.2017.57.html

Current practices to generate tumor-specific T cells in vitro are elaborate and cannot support the treatment of sizable patient populations because a new lymphocyte cohort must be produced for each patient. To overcome these problems, we developed an injectable nanoreagent that can program circulating T cells to recognize tumor antigens.

PROJECT 3: 'Hit-and-run' programing of CAR T cells using mRNA nanocarriers

U.S. Provisional Patent Application No. 62/322,581

We develped a strategy to genetically modify cultured immune cells for therapeutic applications, simply by mixing them with an mRNA-carrying nanoreagent. Our approach provides significant advantages over those currently used to create anti-cancer lymphocytes (i.e., viral transfection and electroporation), which require specialized equipment and demanding production steps; in fact, the expense and difficulty of obtaining these treatments severely limits the availability of immunotherapy for cancer patients.