1 NCI’s Alliance for Nanotechnology in Cancer Program and Resources for Cancer Nanotechnology Research Stephanie A. Morris, Ph.D. Program Director Office of Cancer Nanotechnology Research (OCNR) National Cancer Institute/NIH UPenn Nano/Bio Interface Center September 15, 2015
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NCI’s Alliance for Nanotechnology in Cancer Program and Resources for Cancer
Nanotechnology Research
Stephanie A. Morris, Ph.D. Program Director
Office of Cancer Nanotechnology Research (OCNR) National Cancer Institute/NIH
UPenn Nano/Bio Interface Center September 15, 2015
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Nanotechnology Applications to Cancer: • Potential to revolutionize biomedicine by manipulating materials at the
nanoscale (unique physical, chemical, biological features that differ from bulk)
• Combine innovations in nanomaterials and cancer biology to develop new cancer solutions
• Early detection of disease – Sensors – Imaging
• Delivery of therapeutics – Local and systemic – Improved efficacy – Post-therapy monitoring
• New research tools to enhance understanding of disease
NCI Alliance for Nanotechnology in Cancer (Alliance)
• Supported by NCI’s Office of Cancer Nanotechnology Research • The Alliance works in concert with other NCI advanced technology initiatives to
provide the scientific foundation and team science required to transform cancer research and benefit the patient
Alliance for Nanotechnology in Cancer:
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Phase II Alliance Organization
The Alliance aims to: • Rapidly advance new nanotechnology discoveries into cancer clinical practice by
fostering multi-disciplinary approaches • Aid nanoparticle characterization and standardization of characterization
methods • Develop the next-generation of cancer researchers in the area of
nanotechnology
Centers for Cancer
Nanotechnology Excellence (CCNEs)
U54 Cooperative Agr.
Cancer Nanotechnology
Platform Partnerships U01 Cooperative Agr.
Multi-disciplinary Training K99/R00 Awards, R25
Awards
Nanotechnology Characterization Laboratory (NCL)
NCI Alliance Phase II
• Alliance’s development model—most promising strategies handed off to for-profit partners for effective translation and commercialization
• Phase I: 2005 – 2010 • Phase II: 2010 - 2015
Serves as national resource to aid regulatory review of cancer
nanotechnologies
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Phase II Alliance Objectives
The Alliance focuses on techniques and tools for: • Multifunctional nanotherapeutics and post-therapy monitoring tools • Early diagnosis using in vitro assays and devices • In vivo imaging techniques for early detection and surgical guidance
research discovery
pre-clinical
clinical
• Focus on cancers characterized by low survival rates: pancreatic, ovarian, brain, lung
• Goal of advancing cancer prevention, diagnosis, and treatment
Key Research Goals: • Focus on improving diagnostic detection
and therapeutic index • Overcoming biological barriers (including the
microenvironment) and failure of therapy
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Key Research Topics
• Nano-based vehicles for protein/nucleic acid/drug delivery – Improved pharmacokinetics, reduced toxicity – Targeted to tumor (passive (EPR) and active) – Protection from degradation
• Combination therapies within a single formulation
• Controlled Release of conjugated or encapsulated drug
• Design of vehicles that penetrate biological barriers
BIND Biosciences
Nanotherapeutics
In Vitro Assays/Devices and In Vivo Imaging Techniques
Integrated Blood Barcode Chip—Measurement of GBM biomarker panel (Heath and Hood, Caltech)
• Highly sensitive in vitro nanosensors (proteins, RNAs) to measure diagnostic or prognostic biomarkers
• Multiplexed, multi-modal imaging agents for diagnosis,
surgical resection, and therapeutic monitoring (e.g. In vivo enzyme activity-based assays)
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NCI Alliance for Nanotechnology in Cancer, Phase II
Cancer Nanotechnology Training Centers (CNTCs; R25) (6) Pathway to Independence Award in Cancer Nanotechnology – K99/R00 (7)
Centers of Cancer Nanotechnology Excellence (CCNEs; U54) (9) Cancer Nanotechnology Platform Partnerships (CNPPs; U01s) (12)
Southeast
California
New England
Midwest
West-Southwest
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Office of Cancer Nanotechnology Research: Interactions
• Alliance members also have opportunities to work together through topic-specific working groups (animal models, biotargeting) and Challenge Projects
• OCNR also facilitates interactions between Alliance investigators and other NCI/NIH programs, nanotechnology institutions and organizations
• Significant role in promoting nanotechnology applications to biomedicine by interacting with these programs, other federal agencies (e.g., through NNI) and the wider research community
Translating Genomic Targets in Cancer
Therapeutics Using Nanotechnology
• Connecting investigators in Alliance with investigators in other NCI programs--CTD2 Network
• Exchanging resources, meeting reciprocal needs
PAR-13-185: Image-guided Drug Delivery
in Cancer (R01)
• Developing funding opportunities with other Institutes—NCI and NIBIB
• Advance aspects of image-guided interventions
US-China Symposium on Nanobiology and
Nanomedicine
• Collaboration between NCI, other NIH Institutes, and the NCNST of China
• Explore collaborative opportunities and facilitate discussions on medical nanotechnologies
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NCI Alliance Program - Achievements • Scientific Output
• More than 25 distinct nanomaterial delivery vehicles at various stages of maturity and numerous innovative technologies reported in the literature since 2011
• Over 1000 peer-reviewed journal papers and close to 100 patent filings and disclosures since 2011(close to 1500 papers and 300 patent filings since program start)
• Over 300 different nanoparticle formulations evaluated by the NCI’s Nanotechnology Characterization Laboratory (NCL)
• Clinical Translation
• over 75 companies in the space of diagnostics and therapy are associated with the program. Majority of them are start-ups.
• 17 on-going clinical trials are associated with program projects • Several companies are in IND or pre-IND discussions with US FDA
• Community Resources
• Support for clinical translation—NCL and TONIC consortium • Centralized databases of nanomaterial characterization information—
caNanoLab and Nanomaterial Registry web portals
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Translational Support
• Public–private partnership • Corporate membership--14 industry members
(e.g. Janssen, AstraZeneca, Onyx Pharma, Teva), three patient advocacy group members (e.g., American Brain Tumor Association)
• Bringing Alliance research and TONIC members together
• Discussion forum for opportunities in nanotechnologies and strategies to accelerate translation to clinic
–Workshops –Showcasing of technologies –Joint, pre-competitive projects –Nanodrug Clinical Working Group—
Developing protocols to enable study of drug delivery in patients by imaging
Translation of Nanotechnology in Cancer Consortium (TONIC)
• Pre-clinical characterization of nanomedicines
• Three way agreement of NCI, FDA, and NIST • Supports extramural community • Assisted with characterization leading to six
IND or IDE filings with FDA
Nanotechnology Characterization Laboratory (NCL)
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TONIC Consortium
• Two publications: – Prabhakar et al., 2013, Cancer Research--“Challenges and key considerations of the
Enhanced Permeability and Retention Effect for nanomedicine drug delivery in oncology”
– Gabizon et al., 2014, The Lancet—” Cancer nanomedicines: closing the translational gap”—strategic preclinical and clinical study designs to address the EPR effect question
• TONIC has been credited with facilitating: – interactions with NCL for TEVA and AstraZeneca – Research agreement between Cytimmune and AstraZeneca
Advisory Committee Joseph DeSimone (UNC), Robert
Langer (MIT), Chad Mirkin (Northwestern U),
Larry Tamarkin (Cytimmune), and Vladimir Torchilin (Northeastern U.)
• Collaborations with Pharma, CMOs & industry consortia
Basic Research & Grand Challenges • Immunotox • Active targeting
Metrology & New Methods • Working with instrument manufacturers
• Provides “pharmaceutical mentorship” for materials scientists and engineers
• EU-NCL
Nanomaterials • Other indications, EHS, etc.
Transnational Collaboration
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Nanotechnology Characterization Laboratory: Serving the Community
Standards development efforts in collaboration with NIST, ASTM, ISO, IANH
caNanoLab co-development
Crist et al., Common pitfalls in nanotechnology: lessons learned from NCI's Nanotechnology Characterization Laboratory. Integr Biol (Camb)., 2013
NCL is the only lab evaluating the wide variety of platforms used in nanomedicine. Ten years of providing NCL Assay Cascade testing has given NCL expertise that is unique in the world.
• Realize importance of data sharing and re-use to enable knowledge discovery and improve the rational design of nanomaterials –access to datasets and protocols
Federal Agencies
•National Nanotechnology Initiative (NNI)
Community Interaction
•NCIP Nanotechnology Working Group
Databases •caNanoLab •Nanomaterial Registry
NNI Signature initiative on Nanoinformatics—Nanotechnology Knowledge Infrastructure (NKI): Purpose is to provide a community-based, solutions-oriented knowledge infrastructure by coordinating federal agencies; http://www.nano.gov/NKIPortal
Nanomaterial Data Curation Initiative—Developing data exchange standards, ontologies, community interest; capturing current curation practices and concerns; https://wiki.nci.nih.gov/display/ICR/Nanotechnology+Working+Group
Nanomaterial Data Storage and Sharing—NIH-supported data repositories that facilitate data sharing and re-use in the research community; http://nano.cancer.gov/collaborate/data/
Resources for Nanomaterial Data Sharing and Standards Development
NIH-Sponsored Data Repositories: caNanoLab and the Nanomaterial Registry
Aggregates data from: • Existing publicly-available databases • Patent literature • Manufacturer catalogs Minimal information about a nanoparticle (MIAN)—used to calculate compliance levels, record similarity
www.nanomaterialregistry.org
Supports the annotation of well characterized nanomaterials used in cancer research and treatment • Composition and physico-chemical
information • In vitro/in vivo characterizations • Protocols and publications
cananolab.nci.nih.gov • Started in 2006 • Joint NCI support—Office of Cancer
Nanotechnology Research, Center for Biomedical Informatics and Information Technology
• caNanoLab feeds into Registry • Archives research data on nanomaterials and their biological and environmental implications
• Tools to evaluate content—compliance levels, comparison tools
• Working on integrating modeling and simulation tools for Registry data analysis (nanoHub; http://nanohub.org/)
• Provides data export function to allow easy data download from site and working on data submission page/template; boilerplate text for NSF/NIH data management plans
http://www.elsevier.com/about/mission/innovative-tools/article-of-the-future – Elsevier’s commitment to improve the reader’s experience with online articles—
enriched content, and interoperability with external databases – Linking of scientific journal publications with underlying and/or broader databases
available online—considered critical step in this transition — http://www.elsevier.com/about/content-innovation/database-linking
– caNanoLab is now reciprocally linked to several Elsevier journals (Google “Elsevier and caNanoLab;http://www.elsevier.com/about/press-releases/research-and-journals/elsevier-and-us-national-cancer-institute-implement-reciprocal-linking-between-research-articles-and-datasets) —e.g, Biomaterials, Journal of Controlled Release, Nanomedicine: Nanotechnology, Biology and Medicine
• New online Nature journal—Scientific Data, http://www.nature.com/sdata/
– Focuses on publishing descriptions of data and does so by working with repositories – Gives investigators credit for sharing data – caNanoLab listed as one of their recommended data repositories--
http://www.nature.com/sdata/data-policies/repositories – Editorial Board includes nanotechnology experts: Nathan Baker, Mark Viant
Data Sharing Outreach—Integrating Databases with Journals
Alliance Program Phase III • In addition to the Nanotechnology Characterization Laboratory, three different
components of the program:
NCI Alliance Phase III, 2015-2020
Centers of Cancer Nanotechnology Excellence
(CCNE) U54 Cooperative Agreement
RFA-CA-14-013 $2.6M/yr/award
5-6 CCNEs
Innovative Research in Cancer Nanotechnology
(IRCN) Awards U01 Cooperative Agreement
PAR-14-285 Next applications due October 15, 2015
T32 Cancer Nanotechnology Training Programs
Proposals received through PA-14-015 Next applications due September 25, 2015
$450K/yr/award Multiple Receipt Dates
Notice of NCI interest in Cancer Nano T32s—NOT-CA-14-035
• Initial awards for phase III of the NCI Alliance for Nanotechnology in Cancer program to be made in September 2015—six CCNEs, four IRCNs, and five T32 training programs
CCNEs are expected to (a) identify an overarching problem in cancer biology and/or oncology – a “Center Theme’ that can be addressed with a multi-project approach leveraging nanotechnology and (b) demonstrate the translational potential of the technologies proposed in the above mentioned projects. Expect each to be composed of several projects with a balance between discovery research and translational efforts. The overall goal is a rapid advance of novel cancer care applications based on nanotechnology.
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IRCN U01 Awards
• Projects should be designed to enable multi-disciplinary research and transformative discoveries in cancer biology and/or oncology through the use of nanotechnology
• Funded projects become part of NCI Alliance for Nanotechnology in Cancer network. The network will provide opportunities for collaborations with other Alliance members and enhanced interactions with NCI programs
• If appropriate, work should aid in clinical translation, but clinical translation is not the ultimate goal of these awards
Projects should address major barriers in cancer biology and/or oncology using nanotechnology and should emphasize fundamental understanding of nanomaterial and nanodevice interactions with biological systems. Includes characterization of in vitro detection/diagnostic devices, research concerning delivery of nanoparticles/nanodevices to intended cancer targets in vivo.
Innovative Research in Cancer Nanotechnology
(IRCN) Awards U01 Cooperative Agreement
PAR-14-285; Next applications due October 15, 2015 $450K/yr/award
Two receipts/yr until 2017: April 14, October 13, 2016; April 14, 2017
Open to International Applicants!
No set-aside funds; Not percentiled
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• Development of next generation nanoparticles • Understanding nanoparticle delivery mechanisms and implications of systemic
distribution • Techniques and tools to overcome failure of therapy • Tools and devices aimed specifically at monitoring the tumor microenvironment • Technologies suitable for biomarker discovery and screening • Development of improved multi-biomarker detection and diagnostic devices • Diagnostic nanoparticles/devices that preserve integrity of captured cells and
conformation of isolated molecules for downstream activity assays and analyses • Technologies for cancer molecular targeting, discovery, and validation • Devices and tools capable of penetrating cellular and/or physiological barriers • Integration of modeling and simulation approaches to guide rational nanomaterials
design Above examples are not meant to be comprehensive. Additional directions are also encouraged, providing they are consistent with general expectations of PAR
Possible Research Directions
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Alliance Program Phase III: CCNEs and U01s • NCI intends to continue support for research in three broad areas of
nanotechnology-based cancer care applications: – early diagnosis using in vitro assays and devices or in vivo imaging techniques – multifunctional nano-therapeutics, including nanoparticle-driven immunotherapies – devices and techniques for cancer prevention and control
• Tumor Types: should be rationally selected, where “tumor type” refers to either tumors of a specific tissue of origin or tumors with critical abnormalities in a particular molecular pathway(s) shared in cancers arising from a variety of tissues.
• Milestones: applicants need to provide a set of discrete benchmarks that will allow unequivocal determination of the progress made towards the goals of the project.
• Data Sharing Plan: Sharing of nanomaterial data needs to occur through appropriate publically accessible databases: NCI’s cancer Nanotechnology Laboratory (caNanoLab) data portal (https://cananolab.nci.nih.gov/caNanoLab/)
– At least one scientifically qualified person needs to be designated as the nanomaterial data sharing coordinator after an award has been made
National Cancer Institute Organization: Related Programs and Initiatives
Division of Cancer Biology
Division of Cancer
Prevention
Division of Cancer
Control and Population Sciences
Division of Cancer
Treatment and
Diagnosis
Division of Extramural Activities
Division of Cancer
Epidemiology and Genetics
Center for Cancer
Research
Office of the Director
National Cancer Institute
Funding – Extramural Conducting – Intramural
Center for Strategic Scientific Initiatives
(CSSI)
Acting Director Douglas Lowy, MD
Mission: “…to create and uniquely implement exploratory programs focused on the development and integration of advanced technologies, trans-disciplinary approaches, infrastructures, and standards, to accelerate the creation and broad deployment of data, knowledge, and tools to empower the entire cancer research continuum in better understanding and leveraging knowledge of the cancer biology space for patient benefit…”
• CSSI, Office of the Director • Office of Cancer Clinical Proteomics Research • Office of Cancer Nanotechnology Research • The Cancer Genome Atlas • Office of Cancer Genomics • Office of Physical Sciences Oncology
Innovative Molecular Analysis Technologies
Provocative Questions
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Innovative Molecular Analysis Technologies (IMAT) Program
Program Mission: To support the development, maturation, and dissemination of novel and potentially transformative next-generation technologies through an approach of balanced but targeted innovation in support of clinical, laboratory, or epidemiological research on cancer.
Proof of Principle
Advanced Development
Testing & Validation
Scale Up Dissemination
R21
R33
• Feasibility/Proof-of-principle study • Highly innovative technology • No preliminary data required
• Advanced development & validation phase • Demonstration of transformative utility • Requires proof of feasibility
Technology Development Pipeline
Concept
R43
• Feasibility study • Clear commercial
potential
R44
• Development & (regulatory) validation • Manufacturing & marketing plan • Requires proof of feasibility and
commercialization plan • Demonstration of transformative utility
SBIR Grant Mechanism (PAR-13-327)—Phase I, Phase II, and Fast-Track
[R33] Advanced Development and Validation of Emerging Technologies for Cancer-Relevant Biospecimen Sciences • FOA#: RFA-CA-15-005 • Budget: $900k/3yrs (direct cost cap)
Molecular/Cellular
Analysis Tools
Sample QA/QC
Tools
[R21] Early‐Stage Innovative Molecular Analysis Technology Development for Cancer Research • FOA#: RFA-CA-15-002 • Budget: $400k/3yrs (direct cost cap)
[R33] Advanced Development and Validation of Emerging Molecular Analysis Technologies for Cancer Research • FOA#: RFA-CA-15-003 • Budget: $900k/3yrs (direct cost cap)
• Goal: conduct transdisciplinary research integrating the perspectives of physical scientists (e.g., engineers, chemists, computer scientists, mathematicians, physicists) and cancer researchers to address fundamental questions in cancer research using approaches and theories from the physical sciences.
• A cadre of U01 research projects will contribute to the collaborative Physical Sciences-Oncology Network, includes PS-Oncology Centers (U54s, PAR-14-169).
NCI Research Centers for Cancer Systems Biology Consortium (CSBC)
• The CSBC initiative aims to address challenges of complexity in basic and translational cancer research through the use of experimental biology combined with in silico modeling, multi-dimensional data analysis, and systems engineering.
• Expected to be composed of interdisciplinary teams of scientists (e.g., engineers, chemists, computer scientists) and cancer researchers
• The Consortium will consist of Research Centers, a Coordinating Center (RFA-CA-15-015), and U01 research projects.
U54 mechanism up to $1.5 M (DC)/year for 5 years (RFA-CA-15-014) 2-3 Research Projects 1 Administrative Core 0-2 Shared Resource Cores Outreach Core Pilot Projects
3 Receipt Dates – November 20, 2015; September 9, 2016; April 20, 2017
Enabling Biomimetic Tissue-Engineered Technologies for Integrative Cancer Research
• Upcoming Funding Opportunity (NOT-CA-15-026) - Cancer Tissue Engineering Collaborative (TEC) Research Program focusing on the development and characterization of state-of-the-art biomimetic tissue-engineered technologies for understanding cancer biology, prevention, early detection, diagnosis and treatment.
• The Cancer TEC Research Program will spur collaborative, multidisciplinary projects that engage the fields of regenerative medicine, tissue engineering, and biomaterials with cancer biology.
• NIH Common Fund—Supports high risk research that is synergistic and cross-cutting—support for research, training, development of resources
– https://commonfund.nih.gov/
• Big Data to Knowledge (BD2K)—Common Fund project focused on developing new approaches, standards, methods, tools, software, and competencies to enhance use of biomed Big Data • http://bd2k.nih.gov
• NCI Informatics Technology for Cancer Research (ITCR)—Supports
investigator-initiated informatics technology development for the investigation and management of cancer • http://itcr.nci.nih.gov/
• All have available Funding Opportunity Announcements
• NIH Center for Scientific Review Applicant Resources – http://public.csr.nih.gov/ApplicantResources/Pages/default.aspx – NIH Peer Review Revealed – NIH Tips for Applicants – What Happens to Your NIH Grant Application – NIH Early Career Reviewer Program
• NIH RePORTER
– http://projectreporter.nih.gov/reporter.cfm – Search for applications; Institute, Program Officer, Study Section
• Interested in learning about the NIH grants process in-person? • Researchers, new or early career scientists, or research administrators
interested in learning more about applying for NIH grants, navigating NIH programs, and/or managing NIH awards can meet with ~ 50 NIH & HHS program, policy, grants management, and review experts at the 2015 NIH Regional Seminar in San Diego on October 14-16.