RCT Demonstrates a Hundred-Fold Improvement in Penetration of Solid Tumors Using Therapeutic ABDURINS Compared to Antibodies

Results published in the online journal PLoS ONE (available here)

Research Corporation Technologies (RCT) and collaborators have demonstrated that the small size and long half-life of ABDURIN binders targeting EphA2 on cancer cells leads to a 50- to 150-fold increase in penetration and accumulation into tumors compared to antibodies binding the same target.

The PLoS ONE paper reports the engineering of large and diverse ABDURIN libraries and the use of phage and DNA display to isolate specific, high affinity ABDURINS that bind to the tumor antigen EphA2. Both ABDURINS and antibodies specifically binding EphA2 were labeled with the PET imaging isotope, 64Cu, and administered to mice with tumors expressing EphA2 to determine tumor targeting, penetration, accumulation and biodistribution over 48 hours.

“We were able to efficiently engineer, diversify and isolate a significant number of high affinity ABDURIN binders from both phage and DNA display libraries for therapeutic testing in vivo,” commented Dr. Chris Ullman, senior author and former Chief Scientific Officer at Isogenica, Ltd.

“In this study, the anti-EphA2 ABDURINS, labeled with our PET isotope chelation technology, rapidly located the tumors and accumulated to a much greater extent than a monoclonal antibody against the same target on the cell surface. These results clearly demonstrated that, due to their small size, ABDURINS significantly penetrated tumors better than a larger monoclonal antibody to the same target. Additionally, the long half-life of the ABDURINS delayed clearance from the animals and led to significant ABDURIN accumulation in the tumors at 48 hours. The poor tumor penetration and accumulation of the monoclonal antibody used in the study is consistent with what we have observed for other antibodies we have tested,” stated Matt Harris, co-author and CEO of Clarity Pharmaceuticals.

“These results demonstrate that size and duration do matter when it comes to penetration and accumulation of binders into the tumor tissue. The long half-life of ABDURINS leads to slower clearance from the body and allows more time for the small binders to penetrate and accumulate in the tumor. These properties differentiate ABDURINS from other small protein scaffolds and also show how they should be better suited to deliver drugs or imaging agents into tumors compared to monoclonal antibodies,” stated Dr. Kurt R. Gehlsen, coauthor and Vice President & Chief Scientific Officer at RCT.

ABDURINS (also known as CH2 domains) represent a new class of small protein scaffolds that incorporate antibody-like binding loops, engineered to specifically recognize therapeutic targets of interest while retaining the binding motif used by antibodies to prolong half-life in a patient. As data from this study demonstrate, ABDURINS, at one-tenth the size of monoclonal antibodies, can penetrate into the tumors more efficiently than antibodies over a 48-hour time period. In contrast to other small protein scaffolds, ABDURINS benefit by retaining the same mechanism used by monoclonal antibodies to avoid rapid clearance from the body. This results in better accumulation and uptake into tumor tissues. An ABDURIN half-life of 8 to 16 hours (mAbs. 2012; 4(4): 1-9), while several-fold shorter than for intact antibodies, is more than fifty-fold longer than other small protein binders and antibody fragments, which are eliminated from the body in minutes. The ABDURINS’ delayed clearance renders them more useful as imaging agents or conjugates to carry payloads into tumors than other smaller antibody fragments and scaffolds. RCT plans to partner with industry to develop ABDURINS as the next generation of antibody-like therapeutics.

About RCT

RCT is a Tucson, Arizona-based technology investment and management company that provides early-stage funding and development for promising biomedical companies and technologies. RCT focuses on technology investments with origins from universities and research institutions worldwide. To learn more about RCT and the ABDURIN platform, see www.rctech.com.

About RCT’s Collaborators

Collaborating with RCT on the work published in PLoS ONE are Isogenica, Ltd. (www.isogenica.com); IRBM Science Park,, (www.irbm.it); Clarity Pharmaceuticals, Ltd. (www.claritypharmaceutical.com) ; VTU Technology, (www.vtu.com); and Vascular Biotechnology, Baker IDI Heart and Diabetes Institute, (www.bakeridi.edu.au).

PLoS One Article

Ullman C, Mathonet P, Olesky A, Diamandakis A, Tomei L, Demartis A, et al. (2015) High Affinity Binders to EphA2 Isolated from Abdurin Scaffold Libraries; Characterization, Binding and Tumor Targeting. PLoS ONE 10(8): e0135278. Doi:10. 137/journal.pone.0135278 (available here).


Research Corporation Technologies
Rebecca Buescher, 520-748-4411

Posted in AZBio News, In the Loop.