Volume 5, Issue 4: July 2016
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Inside This Issue

  1. Break Through
  2. Pressing Matters
  3. Meeting Center
  4. Awards Spotlight
  5. Molecular Link
  6. On the Horizon
  7. InSite
  8. Get Involved

President's Message

Cynthia Dunbar, MD

Mary Dean, JD, CAE

Dear ASGCT Members,

In recent months ASGCT has initiated several collaborative projects, all focused on furthering our mission and highlighting our society as the “go to” organization for expert, unbiased and timely information on cell and gene therapies. These initiatives target patients, medical providers, and funders, all necessary to the future growth and success of human gene and cell therapies.

Patient Education
We are partnering with the Hemophilia Federation of America (HFA) to produce a series of webinars explaining basic concepts in hemophilia gene therapy, targeting hemophilia patients, their families and friends. Our recent survey of disease foundations indicated a real unmet need for unbiased, honest and patient-directed educational materials to help patients understand how gene therapy might impact now and in the future on their disease. We are excited to work with HFA on the first of what we hope will be a series of patient-directed webinars. The webinars will be widely publicized via HFA patient outreach, and presented at meetings around the country as well as being made available through ASGCT and HFA web archives for maximum outreach value.

Healthcare Provider Education
Working together with the Foundation for the Accreditation of Cellular Therapy (FACT), ASGCT representatives are developing a webinar aimed at educating technicians and other personnel working in laboratories, blood banks and pharmacies on what they need to know about handling engineered T cell products, such as CAR T cells.

In addition, FACT has published a draft of the first edition FACT Standards for Immune Effector Cell Administration, which are intended to promote quality in administration of immune effector cells and will be incorporated into a voluntary FACT accreditation for healthcare facilities preparing cell therapy products. Relevant ASGCT committees are preparing official comments to FACT; however, individual ASGCT members are welcome to submit their comments as well. Read the draft standards and submit your comment through September 9, 2016 by following the instructions on FACT’s Request for Public Review and Comment document.

Funder Education
In anticipation of the National Academy of Science (NAS) report on genome editing, senior staffers of the US Senate Committee on Health, Education, Labor & Pensions (HELP Committee) have asked for education regarding basic concepts in genome editing. Our newly constituted Government Relations and Genome Editing Committees will work with a medical writer to produce a white paper and subsequent in-person briefing on genome editing for HELP Committee staffers this October.

Get Involved!

If you have an interest in becoming involved with any of these activities or know of other important initiatives in which ASGCT should be involved, please contact us by emailing or calling ASGCT Executive Director, Mary Dean.

You are always welcome to participate in ASGCT member programs through the online Get Involved section of the ASGCT website.


Cynthia Dunbar, MD
ASGCT President

Mary Dean, JD, CAE
ASGCT Executive Director

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Letter From the Editor

Dear ASGCT Colleagues,

For those who are interested in genome editing and gene therapy, one essential question is whether or not genome editing is safe enough for a clinical trial? We know that day will come sooner or later, but when?  At the end of this June, a clinical trial proposed by Dr. Edward Stadtmauer (Physician) and Dr. Carl June (Scientific Advisor) from the University of Pennsylvania received a  green light from NIH’s Recombinant DNA Research Advisory Committee (RAC). This proposal is currently waiting for FDA approval. Several weeks later, China reported exciting news that the first CRISPR genome editing trial on humans had been approved by the China Food and Drug Administration (CFDA). Since its debut, genome editing has become a game-changer and has significantly accelerated our research in gene and cell therapy to develop more precise therapeutic treatments. Please refer to our InSITE section for the latest breaking news in the field.  

As the leading voice in the gene and cell therapy field, ASGCT has partnered with several organizations to pave the roads for human gene and cell therapy.  Among these organizations, the Hemophilia Federation of America (HFA) and the Foundation for the Accreditation of Cellular Therapy (FACT) have both collaborated with ASGCT in order to provide education on gene and cell therapy for patients and healthcare professionals. In the President’s Message of this issue, you will see more details about our society’s efforts to promote gene and cell therapy. 

Cancer immunotherapy has become the hottest field for developing therapeutic cancer treatment. Several immunotherapy drugs have recently been approved by the FDA. Recently, a new approach has been developed using the systemic nanopartical to deliver tumor antigen-encoding mRNA to mimic the infection in order to battle cancer. In this issue's Breaking Through section: Dr. Lena Kranz and her colleagues from the Johannes Gutenberg University summariz their recent findings published in Nature: “Systemic RNA delivery to dendritic cells exploits antiviral defense for cancer immunotherapy”. Please refer to the Breaking Through section of this issue to read more about this exciting finding.

In this issue’s Pressing Matters section, Molecular Therapy highlights single-cell monitoring of siRNA targeting efficiency and the threshold of siRNA dosage to induce cell deaths in several leukemia cell lines.  This is one of the few studies about quantitative dosage for cell death at a single cell level.

Also, for those of us who weren’t able to attend all of the sessions at ASGCT’s 19th Annual Meeting, check out the Meeting Center section to read Annual Meeting session summaries.

In the Award Spotlight section, you will learn more about ASGCT’s 2016 Outstanding New Investigators: Dr. Marcin Kortylewski and Dr. Junghae Suh.

I hope you will take the time to read through this issue of The Vector. As always, please feel free to contact me with feedback or content that would be of most interest to you.


Zhongya Wang, PhD
Editor of The Vector

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Breaking Through

A message for immunity: Systemic nanoparticle RNA vaccines mimic infection to fight cancer

Nature 534, 396-401 (16 June 2016)

Lena M. Kranz                     Christian Grunwitz                  Robert A. Jabulowsky
Mustafa Diken                     Mathias Vormehr                    Sandra Heesch
Heinrich Haas                     Yves Hüsemann                     Jessica Hassel
Sebastian Kreiter                Abderraouf Selmi                    Peter Lengguth
Carmen Loquai                   Andreas N. Kuhn                    Stephan Grabbe
Kerstin C. Reuter                Janina Buck                             Christoph Huber
Martin Meng                         Evelyna Derhovanessian      Ozlem Türeci
Daniel Fritz                           Richard Rae                            Ugur Sahin
Fulvia Vascotto                    Sebastian Attig
Hossam Hefesha              Jan Diekmann

Summary written by:
Lena M. Kranz, Mustafa Diken, Özlem Türeci and Ugur Sahin

Mechanisms of antiviral host defense are important for survival and evolutionarily optimized for high sensitivity and potency. Cellular immune responses such as cytotoxic effector T cells are able to target virally infected cells directly and eradicate the cellular reservoir of the pathogen, ultimately terminating pathogenic persistence. Antigen-specific cancer immunotherapy has recognized the significance of cellular immune responses, and the induction of tumor-specific effector T cells that reduce tumor mass and induce immunological memory to control relapse has thus become the common aim in therapeutic tumor vaccination. Many initial attempts for cancer vaccines were not successful mainly due to a rather poor understanding of the underlying mechanisms and choice of vaccine formats and adjuvants. In the last two decades, enormous progress has been made in this field, and current studies on vaccines are designed more rationally.

Dendritic cells (DCs) have an exceptional ability to internalize different forms of antigens, which, when encountered in the presence of ‘danger signals’, are able to induce full maturation and presentation of antigen on MHC class I and II. Following recognition of their cognate antigen, CD4 and CD8 T cells proliferate and differentiate into tumor-specific effector T cells.  As the significance of DCs in bridging innate and adaptive immunity is well established, many vaccine strategies target DCs directly or indirectly for the induction of antigen-specific immune responses.

Among these, tumor antigen-encoding mRNA, which can be easily and cost-effectively produced via in vitro transcription, excelled as a vaccine format thanks to its unique properties. mRNA not only delivers the full antigenic information without the risk of genomic integration but also stimulates the immune system as a vaccine adjuvant. Local vaccination with mRNA (intranodal, intradermal) has already been shown to induce potent T cell immunity and has reached clinical setting. Nevertheless, local vaccine application restricts the target population to a limited number of skin- and lymph node-resident DCs, constraining the strength of the induced T cell response.

Intending to unleash the full potential of mRNA vaccination, Kranz et al set out to exploit the central role of DCs on the systemic level by directing mRNA uptake selectively to DCs in lymphoid compartments body-wide. Upon intravenous injection, lipid-formulated, tumor antigen-encoding mRNA nanoparticles (RNA-lipoplexes (RNA-LPX)) were directed to various lymphoid tissues, including the spleen, lymph nodes and bone marrow, which provide the ideal microenvironment for efficient priming and amplification of T cell responses. Solely the RNA-to-lipid ratio was discovered to determine the biodistribution of RNA-LPX, irrespective of the types of lipids used, and a slightly negative particle net charge was able to specifically transfect lymphoid-resident antigen presenting cells (APCs). Uptake by CD11c+ DCs, plasmacytoid (p)DCs and macrophages in the marginal zone of the spleen and in other lymphoid organs, predominantly by macropinocytosis, was followed by RNA recognition via Toll-like receptor (TLR) 7, an endosomal single-stranded RNA-specific pattern recognition receptor (PRR) serving signaling cascades that prepare for antiviral defense mainly through type I interferon (IFNα and β).

Two transient waves of type I IFN production by pDCs (early response) and macrophages (delayed response) established an inflammatory milieu reminiscent of that initiated during the early systemic phase of viral infection. These IFNα receptor (IFNAR)-dependent immune mechanisms stimulated maturation and migration of DCs into the T cell zones, as well as promoted the induction of functional antigen-specific T cells. Antigen expression and presentation on MHC class I and II in the context of upregulated CD40, CD69 and CD86 elicited strong effector and memory CD8 and CD4 T cell immunity against viral, mutant neo-antigens or self-antigens, which was able to reject progressive tumors in therapeutic mouse models of melanoma, colon carcinoma and human papilloma virus (HPV)-associated cancer.

In an ongoing phase I dose escalation study, the first cohort of three patients with advanced melanoma received RNA-LPX encoding four shared tumor antigens starting with an extremely low dose (lower than the total amount of RNA-LPX used in the mouse studies). All patients showed a dose-dependent IFNα- and IP-10-dominated cytokine response, developed de novo CD4 and CD8 T cell responses or enhanced pre-existing immunity against the encoded self-antigens NY-ESO-I, Tyrosinase and MAGE-A3. These results support the preclinically identified mode of action and strong potency of this approach in the clinical setting.

The study presents a novel class of systemically administered nanoparticulate RNA vaccines acting by body-wide delivery of encoded antigens to APCs and simultaneous initiation of a strong type I IFN-driven immunostimulatory program. Precise DC targeting in lymphoid compartments is accomplished using well-known lipid carriers and only by manipulating the net charge of the nanoparticles. RNA-LPX vaccines appear to mimic infectious non-self and thus mobilize both adaptive and innate immune mechanisms, connecting effective cancer immunotherapy with host pathogen-defense mechanisms. The highly versatile design allows vaccine preparation with any type of RNA-encoded antigen and may thus be regarded as a universally applicable vaccine approach for cancer immunotherapy.

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Pressing Matters

  Read highlights from the latest issue of Molecular Therapy, the official journal of

  Also, explore the open access, online-only companion journals to Molecular Therapy:

   Click here to visit the Molecular Therapy page on Nature Publishing Group's


Molecular Therapy: Methods & Clinical Development -  Upcoming Special Issue: Development of Cell Therapies

Guest editors: Bruce Levine, Andrew Fesnak, and Isabelle Riviere

Cell therapies, including use of gene-modified cells and various types of stem cells, have become an integral part of modern medicine. Applications range from correction of genetic disease to cancer therapy. Novel technologies such as induced pluripotent stem cells are in early clinical development. This open access special issue of Molecular Therapy – Methods & Clinical Development will cover innovative technologies that are being developed in academic centers and in the biotech sector for development and manufacturing of cell therapies.

MTM is now accepting article submissions for our special issue on development of cell therapies, including the innovations--for applications ranging from correction of genetic disease to cancer therapy--that are now underway in academic centers and the biotech sector. Potential authors are encouraged to submit before September 30, 2016.

To submit an article, please visit: http://mts-mtm.nature.com/cgi-bin/main.plex

Featured Molecular Therapy Articles

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Meeting Center

19th Annual Meeting Session Summaries
Thank you again to all of the attendees, faculty, exhibitors, and sponsors who helped make ASGCT's 19th Annual Meeting the best yet! Read below for summaries of the Annual Meeting symposia:

ASGCT and ESGCT Clinical Trials and Commercialization Workshop
Florence, Italy
Tuesday, October 18, 2016

As part of the European Society of Gene and Cell Therapy (ESGCT) 2016 Annual Congress, ASGCT and ESGCT will hold a joint Clinical Trials and Commercialization Workshop on October 18th, 2016, in Florence, Italy. This half-day Workshop will explore the following topics:

Stay tuned for more details and visit the ESGCT Annual Congress website to register for the ASGCT and ESGCT Clinical Trials and Commercialization Workshop.

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Awards Spotlight

Awards Spotlight - 2016 Outstanding New Investigators
The Outstanding New Investigator Award recognizes ASGCT Members who are newly independent researchers. Two of this year's ONI award winners, Dr. Marcin Kortylewski and Dr. Junghae Suh talk about their research and experience with ASGCT:

Marcin Kortylewski, PhD
City of Hope Comprehensive
Cancer Center

  Describe your research interests:
  My research group focuses on the development of cell-selective oligonucleotide
  strategies to jump start immune responses against advanced tumors. In particular,
  we are targeting STAT3, an oncogene and the central regulator of tumor immune
  evasion. The first two generation of our oligonucleotide CpG-STAT3 inhibitors, siRNA-
  and decoy DNA-based, are currently in IND-enabling preclinical studies here at City
  of Hope (Duarte, CA). We are focusing on hematologic malignancies and certain
  type of solid tumors, such as prostate cancer. At the same time, we continue to
  validate new molecular targets for this strategy among other transcriptional
  regulators as well as miRNA.

  Briefly describe how you reached your current position (educational background):
  After receiving MS in Biotechnology (AMU, Poznan, Poland), I joined the Institute of
  Biochemistry at the RWTH Aachen in Germany led by Prof. Peter Heinrich. There, I
  focused on on the STAT3 transcription factor, identified earlier by this group as a crucial mediator of IL-6 signaling.
  After receiving Ph.D. and an additional post-graduate work in Aachen, I moved overseas for postdoctoral training
  with Drs. Hua Yu and initially Richard Jove in Moffitt Cancer Center (FL). There, I started to gradually shift away from
  cancer biology to focus on the role of Jak/STAT signaling in tumor-associated immune cells. These studies
  eventually defined STAT3 as a master immune checkpoint regulator and an ideal target for cancer immunotherapy,
  now pursued by my own research group at City of Hope.

  To read more of Marcin Kortylewski's interview, please click here.

Junghae Suh, PhD
Rice University

  Describe your current research interests:
  When I started my independent career at Rice, I had one foot in the synthetic
  nanoparticle field and the other foot in the virology field. The question remained how
  to combine the two domains into a meaningful and impactful research vision. The
  answer came in the form of an article written by Yuri Lazebnik for Cancer Cell (“Can
  a biologist fix a radio?”), which definitively transformed my research approach. This
  article led me to reviews and commentaries about a relatively new field called
  synthetic biology. The moment I realized I can, and should, apply engineering
  thinking to the design of viruses was both clarifying and energizing. I now combine
  my knowledge of viruses with a decidedly engineering design approach, and treat
  viruses as programmable nanodevices with defined inputs and outputs. In
  particular, my lab focuses on reprogramming the adeno-associated virus (AAV) as
  controllable gene delivery vectors.

  Briefly describe how you reached your current position (educational background):
  My undergraduate degree was in Chemical Engineering from MIT. I was pretty clueless the first 3 years of college
  and I was just in survival mode – just trying to make it to the next problem set due date. During the summer after
  my junior year, however, it dawned upon me that I really enjoy biology, so as soon as I returned to campus I
  pursued a minor in Biology and applied to PhD programs in Biomedical Engineering (BME). Even with my naïve
  understanding of how things worked, I still thought that being at the interface of biology and engineering would be
  cool. The stars magically aligned and I got accepted into the Johns Hopkins School of Medicine BME PhD program.
  Towards the end of my PhD working on synthetic polymer-based gene delivery systems, I realized that I was always
  struggling to make and compare our synthetic systems to match the innate abilities of viruses. In one of my
  moments of frustration, I wondered why I was trying to recreate the wheel when I can just take viruses and adapt
  them for gene therapy use. Therefore, for my postdoc I decided to jump the fence and learn about viruses – in
  particular the adeno-associated virus (AAV).

  To read more of Junghae Suh's interview, please click here.

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Molecular Link

ASGCT Job Bank
As a student or postdoctoral fellow, the ASGCT Job Bank allows you to search for gene and cell therapy positions and post your resume so employers can search for you. Members can post positions and view resumes at a reduced rate. Take advantage of this area to grow your professional development. Below are three recent job postings to the ASGCT online job bank, your link to the latest career opportunities within gene and cell therapy.

Click here to visit the ASGCT Job Bank and view the complete list of current career opportunities.

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On the Horizon

ASGCT 20th Annual Meeting
Save the date for the ASGCT 20th Annual Meeting! The meeting will be held at the Marriott Wardman Park in Washington, DC, May 10-13, 2017. ASGCT is pleased to present plenary speakers Robert Langer, PhD, from the Massachusetts Institute of Technology (MIT), and Eric Olson, PhD, from the UT Southwestern Medical Center at Dallas. Stay tuned for more details on the plenary lectures, program, abstracts, and more!

Upcoming Non-ASGCT Events of Interest

International Society  for Differentiation
Boston, MA
August 4 - 8, 2016
Click here for more information.

Genomic Medicine Conference
HudsonAlpha Institute for Biotechnology
Huntsville, Alabama
August 8 - 10, 2016
Click here for more information.

International Society for Experimental Hematology
San Diego, CA
August 25 - 28, 2016
Click here for more information.

Oligonucelotide Therapeutics Society
Montreal, QC, Canada
September 25 - 28, 2016
Click here for more information.

9TH Stem Cell Clonality and Genome Stability Retreat
Florence, Italy
October 17 - 18, 2016
Click here for more information.

ESGCT and ISSCR Congress
Florence Italy
October 18 - 21, 2016
Click here for more information.

3rd IABS Conference on Cell Therapy Manufacturing and Testing
London, United Kingdom
November 2 - 3, 2016
Click here for more information.

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FACT Call for Comments
The Foundation for the Accreditation of Cellular Therapy (FACT) has released the 1st edition draft of the FACT Standards for Immune Effector Cell Administration for inspection and public comment. Comments will be accepted for a 60-day period from July 12, 2016 through September 9, 2016. These Standards are intended to promote quality in administration of immune effector cells and will be incorporated into a voluntary FACT accreditation in this field. For more background information on this document, please click here.

Available Documents for Review
The following draft documents are available for public comment and review:

  1. Draft FACT Standards for Immune Effector Cell Administration, 1st Edition: This document includes the entire set of requirements proposed for implementation.
  2. Draft FACT Immune Effector Cell Accreditation Manual, 1st Edition: This document provides guidance information to explain requirements, describe the types of evidence that may be required, and outline examples of ways to comply.

Instructions for Submitting Comments
To submit comments regarding the draft 1st edition FACT Immune Effector Cell Standards, access the Comment Form at http://goo.gl/forms/HCgXvDuG3CoAPWoz2

Dieter C. Gruenert Scientific Research Fund
A longtime ASGCT Member and leader in the field, Dr. Dieter Gruenert passed away unexpectedly on April 10, 2016. A memorial service for Dr. Gruenert is being planned for Sunday, August 28, 2016. Details for the memorial service can be found here.

Dr. Gruenert's family has established a Scientific Research Fund in his honor. If you would like to make a contribution to the Dieter C. Gruenert Scientific Research Fund, please send an email to dcgsrf@gmail.com.

Industry News

Follow Us
Follow ASGCT on Twitter and like our Facebook page for up-to-date publications, news in the field of gene and cell therapy, and updates on Society events.

Join ASGCT's Official LinkedIn group to connect with the best in the field, discuss key issues, grow your personal network, and post open jobs.

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Get Involved

Become a Member
Renew your Membership for 2016 and join us for another exciting year in the growing field of gene and cell therapy! Do you have colleagues interested in joining ASGCT? Send them information on becoming a member and encourage your colleagues to turn their interest into involvement.

Volunteer to Serve on an ASGCT Committee
ASGCT is excited to offer its Members the ability to self-nominate or submit recommendations of individuals to serve on committees within ASGCT. To submit a recommendation or to volunteer to serve on an ASGCT Committee, please complete this form.

Suggest Annual Meeting Speakers and Symposia
Help make ASGCT's 20th Annual Meeting a success! ASGCT offers its members the ability to submit symposia and presentation recommendations to ASGCT for the upcoming Annual Meetings by filling out the following form.

Submit Your Press Release
In order to increase publicity for gene and cell therapy, ASGCT would like to issue press releases for clinical trials results as they emerge in the field. Our hope is that by increasing exposure of the positive results in the field, we can grow public awareness of gene and cell therapy. ASGCT welcomes written communications from partnering institutions and ASGCT  Member researchers sharing the commitment to advancing the treatment of human diseases. Please visit the ASGCT website to submit your press release.

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