Unique characteristics of nanoparticles make them highly attractive for various applications in oncology. They are able to function as carriers for chemotherapeutic drugs to increase their therapeutic index and lower their toxicity, as therapeutic agents
in photodynamic, gene, and thermal therapy, as well as molecular imaging agents to detect and monitor cancer progression. Several nanoparticle-based agents for cancer therapy and diagnostics have been approved by FDA, more are in clinical trials,
and even more are in the discovery and early development stages in academic and industry laboratories. Cambridge Healthtech Institute’s Latest Advances in Nano-Oncology symposium is designed to encourage open discussion and knowledge exchange
in this exiting and rapidly developing area at the junction of nanobiotechnology and oncology.
Tuesday, June 14
8:00 am Registration and Morning Coffee
9:00 Chairperson’s Opening Remarks
Dai Fukumura, M.D., Ph.D., Deputy Director, Edwin L. Steele Laboratory; Biologist, Department of Radiation Oncology, Massachusetts General Hospital; Associate Professor, Harvard Medical School
9:15 Nanoparticle Drug Conjugate Development
Richard Wooster, Ph.D., President R&D and CSO, Tarveda Therapeutics, Inc.
With the Pentarin platform, Blend creates novel, miniaturized biologic drug conjugates that incorporate innovative targeting ligands linked to potent cancer cell-killing payloads. Pentarins are designed to have optimal therapeutic properties while remaining
miniature in size, enabling deep penetration into solid tumors to cause cancer cell death.
9:45 Efficient Gene Silencing Using Self-Assembled Rosette Nanotubes
Hicham Fenniri, Ph.D., Professor, Chemical and Biomedical Engineering Northeastern University
Supramolecular engineering is the art of constructing well-deﬁned macromolecular architectures from small components through directed self-assembly and self-organization processes. For example hydrogels, nanotubes, nanocapsules, bioactive scaﬀolds and
many more can be created from simple but carefully crafted building blocks. This lecture will focus on a new class of heteropolycyclic molecules designed to self-assemble into nanotubes and hydrogels for targeted drug delivery, tissue engineering,
and gene silencing.
10:15 Rational Optimization of Nanoparticle Formulations
Arijit Chakravarty, Ph.D., Director, Modeling and Simulation (DMPK), Takeda Pharmaceuticals
Nanoparticle-based drug delivery promises many benefits, such as the ability to overcome biological barriers, preferentially target disease sites, reduce toxicity, and protect drugs from degradation. However, the translational projection of these potential
benefits is challenging, and they are not easy to demonstrate directly in clinical practice. This presentation will focus on the use of PK/PD modeling in the rational projection and optimization of nanoparticle benefit in the Oncology setting.
10:45 Coffee Break
11:15 Super Enhanced Permeability and Retention (SUPR) Effects in Tumors Following Near Infrared Photo-Immunotherapy
Hisataka Kobayashi, M.D., Ph.D., Chief Scientist, Molecular Imaging Program, NCI/NIH
The delivery of nano-sized therapeutic agents to cancers largely relies on enhanced permeability and retention (EPR) effects with limited success in oncology. Near infrared photo-Immunotherapy (NIR-PIT) is a recently developed therapy that treats
tumors with light therapy and subsequently causes an increase in nano-drug delivery up to 24-fold compared with untreated tumors that names super-enhanced permeability and retention (SUPR) effects. SUPR effects could enhance delivery into tumor
beds of a wide variety of nano-sized agents.
11:45 Exploiting and Taming Tumor Microenvironment for Nanotherapy
Dai Fukumura, M.D., Ph.D., Deputy Director, Edwin L. Steele Laboratory; Biologist, Department
of Radiation Oncology, Massachusetts General Hospital; Associate Professor, Harvard Medical School
Abnormal tumor vasculature and microenvironment form formidable barriers to anti-tumor therapies. One can design nanotherapeutics to exploit such abnormalities such as a multistage nanoparticle delivery system that uses enhanced permeability and
retention effect for selective delivery to tumors, and tumor specific enzymes to release and advance small nanoparticles. One can also “normalize” tumor vasculature by correcting imbalance of pro- and anti-angiogenic factors, and
thus improve nanotherapeutics delivery and efficacy.
12:15 pm Enjoy Lunch on Your Own
2:00 Chairperson’s Remarks
Bruce R. Zetter, Ph.D., Charles Nowiszewski Professor of Cancer Biology, Department of Surgery, Harvard Medical School
2:10 Applying Nanotherapeutics to Improve Chemoradiotherapy Treatment for Cancer
Andrew Wang, M.D., Associate Professor, Director of Clinical and Translational Research, Department
of Radiation Oncology, Lineberger Comprehensive Cancer Center, University of North Carolina,Chapel Hill
One strategy to further improve chemoradiotherapy is to preferentially deliver chemotherapeutics to tumors while avoiding normal tissue. While this was not possible with traditional drug delivery techniques, nanotherapeutics provided a unique
opportunity. Our group has demonstrated that nanoparticle delivery of chemotherapeutics are more effective and less toxic than small molecule chemotherapy in chemoradiation. With such preclinical data, we have initiated a clinical trial evaluating
a nanotherapeutic (CRLX101) in chemoradiotherapy treatment for rectal cancer.
2:40 Novel Combinations with CRLX101, an Investigational Nanoparticle Drug Conjugate of Camptothecin
Lata Jayaraman, Ph.D., Director, Pharmacology and Translational Research, Cerulean Pharma
CRLX101, an investigational nanoparticle-drug conjugate (NDC) containing the payload camptothecin, is currently being evaluated clinically in multiple solid tumors. Dosed in over 300 patients, CRLX101 has not demonstrated significant toxicity
and thus offers a unique opportunity to improve cancer treatment in a meaningful way. Given its tolerability profile to date, we have explored pre-clinical, and more recently, clinical combinations of CRLX101 with multiple classes of drugs
including VEGF inhibitors and PARP inhibitors. These data will be discussed.
3:10 Preclinical Characterization of DCR-BCAT, an Optimized Nanoparticle Formulation Containing a β-Catenin-Targeting RNAi Trigger
Shanthi Ganesh, Ph.D., Associate Director, Pre-Clinical Oncology, Dicerna Pharmaceuticals
DCR-BCAT is a preclinical development candidate that targets CTNNB1, the gene which encodes β-catenin. Here we present PK/PD, efficacy, mechanism of action, and tolerability data for this advanced RNAi nanoparticle formulation. DCR-BCAT,
either as a monotherapy or combination therapy, effectively demonstrated antitumor activity and mRNA knockdown in xenograft and GEMM tumors of diverse origin, including experimental metastasis. In this presentation, we will explore the parameters
which yielded a promising nano-oncology therapeutic suitable for clinical evaluation, and discuss future directions.
3:40 Refreshment Break
4:00 Nanotechnology-Mediated Biomolecular Delivery for Cancer Therapy
Jinjun Shi, Ph.D., Assistant Professor, Harvard Medical School, Director, Laboratory for Nanoengineering
& Drug Delivery, Brigham and Women’s Hospital
Dr. Shi’s laboratory research involves a highly interdisciplinary combination of nanotechnology, biomaterials, drug delivery and Immunotherapy. In the presentation, he will discuss some of his recent work in developing robust nanoparticle
platforms for systemic in vivo delivery of nucleic acids, oral delivery of biologic therapeutics and the design of synthetic vaccines. These nanotechnology-mediated biomolecular delivery strategies hold significant potential for the development
of various cancer nanotherapies.
4:30 Targeting the Vasculature and Extracellular Matrix Improve the Distribution and Effectiveness of Oncolytic Virus in Tumors
Yves Boucher, Ph.D., Associate Professor, Radiation Oncology, Harvard Medical School
Although nanotherapeutics and oncolytic virus have offered new hope for cancer treatment, their clinical efficacy is modest. This is partly due to intratumoral barriers – like the vasculature, extracellular matrix (e.g. collagen fibers)
and cancer cells – which hinder the penetration / distribution of large therapeutics in cancer lesions. Here, I will focus on how the targeting of extracellular matrix – angiotensin II signaling – and vasculature enhance
the anti-tumor effectiveness of oncolytic virus.
5:00 Close of Symposium