Abstract 3674: Pentarins: Improved tumor targeting through nanoparticle encapsulation of miniaturized biologic drug conjugates

• Published in: Cancer research (Chicago, Ill.) Vol. 75; no. 15_Supplement; p. 3674
• Main Authors: Bilodeau, Mark T., Shinde, Rajesh, White, Brian, Bazinet, Patrick, Whalen, Kerry, Dupont, Michelle, Kriksciukaite, Kristina, Quinn, Jamie, Sweryda-Krawiec, Beata, Alargova, Rossitza, Brockman, Adam, Lim Soo, Patrick, Meetze, Kristan, Moreau, Benoit, Oller, Haley, Ramstack, Mike, Rockwood, Danielle, Singh, Sukhjeet, Yeung, Tsun Au, Kadiyala, Sudha, Dunbar, Craig, Wooster, Richard
• Format: Journal Article
• Language: English
• Published: 01-08-2015
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/1538-7445.AM2015-3674

The specific targeting of cytotoxic drugs to solid tumors has achieved success with the advent of antibody drug conjugates (ADCs). This approach has had notable success but has also met with limitations. The most common issue limiting ADC effectiveness is believed to be low tumor permeation by these large (∼150 kDa) molecules. Attempts to address this limitation have been focused on the design of miniaturized biologic drug conjugates such as those with small protein or small molecule targeting moieties. However, these efforts uniformly result in conjugates with poor pharmacokinetics in contrast to the extended plasma pharmacokinetics observed with ADCs. The Pentarin platform encapsulates miniaturized biological drug conjugates within nanoparticles to improve the biodistribution of these classes of conjugates. There are multiple benefits to this strategy. Through the enhanced permeability and retention (EPR) effect the nanoparticles accumulate in the perivascular space of the tumor tissue. Next the nanoparticles release the permeable miniaturized conjugate that can penetrate in to the tumor, bind to an over-expressed target on the cancer cell surface, internalize the payload and elicit a strong biological effect. All of this is further enhanced by the extended plasma pharmacokinetics of the nanoparticle when compared to the conjugate alone. To exemplify the Pentarin platform we have designed novel miniaturized biologic drug conjugates to an over-expressed target found in small cell lung cancer. In vitro data has shown the designed conjugates specifically and potently target tumor cells expressing the receptor of interest. When encapsulated in nanoparticles, these miniaturized biologic drug conjugates have improved plasma pharmacokinetics, the amount of payload delivered to xenograft tumors is increased and the xenograft efficacy is significantly more pronounced over drug conjugate not in a nanoparticle. These observations correlate with in vivo mechanistic assays in the xenograft tissue. These data will be presented, together with the name of the target, to demonstrate the impact of the Pentarin platform and to show progress towards the first clinical candidate from this work.
Citation Format: Mark T. Bilodeau, Rajesh Shinde, Brian White, Patrick Bazinet, Kerry Whalen, Michelle Dupont, Kristina Kriksciukaite, Jamie Quinn, Beata Sweryda-Krawiec, Rossitza Alargova, Adam Brockman, Patrick Lim Soo, Kristan Meetze, Benoit Moreau, Haley Oller, Mike Ramstack, Danielle Rockwood, Sukhjeet Singh, Tsun Au Yeung, Sudha Kadiyala, Craig Dunbar, Richard Wooster. Pentarins: Improved tumor targeting through nanoparticle encapsulation of miniaturized biologic drug conjugates. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3674. doi:10.1158/1538-7445.AM2015-3674