Last Updated: 10/02/2023

STAFF HIGHLIGHT: The Biological Resources Branch in DCTD’s Developmental Therapeutics Program

In this edition of the DCTD newsletter, we hear from staff in the Biological Resources Branch (BRB), one of the nine branches in DCTD’s Developmental Therapeutics Program (DTP).

Jason Yovandich, PhD, Branch Chief
To provide a historical perspective, BRB used to be in the fold of the Biological Response Modifiers Program (BRMP), which was established in the early 1980s in DCTD when it was known as the Division of Cancer Treatment. As BRMP’s biological product arm, BRB’s focus was to procure novel therapeutics through contract mechanisms for NCI-supported clinical trials. BRB’s previous branch chief, Dr. Steven Creekmore, who retired in 2017, ran some of those trials for BRMP. Drs. Toby Hecht and Craig Reynolds were in BRB at that time as well. Toby went on to become the associate director of DCTD’s Translational Research Program and DCTD’s deputy director and Craig became the associate director for the Office of Science Operations at Fort Dietrick.

BRMP dissolved in the mid-1980s, and BRB became part of DTP. Dr. Rose Aurigemma, DTP’s current associate director, joined BRB in 2001 as a program director (PD) and worked on virus products, and that was around the time when BRB started working on viral vector production. I was a Cancer Research Training Award (CRTA) fellow doing post-doctoral work here then, and Dawn Edwards and Dr. Ray Harris, both part of BRB now, were also on staff. Rose and Ray spent some time at NIAID, but both returned to DTP — Rose in 2017 and Ray in 2019. Rose is now DTP’s associate director, and Ray is a PD in our branch. I stayed on after my post-doctoral work as a PD and became branch chief about four years ago. My experience in BRB shows that there is a lot of potential for personal growth in our branch.

BRB’s Focus Areas
BRB staff understand the complexities of translational science for biologics and contracts. They have a high level of experience related to manufacturing biologics, proteins, viruses, and vaccines for cancer treatment and other NIH priorities. This expertise is required for BRB to support the DTP mission in its three connected focus areas:

• A grant portfolio that consists of mostly research project grants and some program project grants and cooperative agreements
  The branch has approximately 130 active grants split among four PDs. Each grant portfolio is assigned to a PD based on the PI’s last name instead of research area or PD expertise. This allows BRB staff to manage a variety of science and technology development projects instead of just one area.

• A preclinical repository that stores and distributes (free of charge) biological reagents to academic and non-profit researchers for use in preclinical research
  NIH, academia, and industry donate the high-quality reagents to the repository for distribution to the scientific community. In 2022, the repository received 174 domestic orders resulting in distribution of 3,279 vials of materials (antibodies, cytokines, growth factors, and recombineering reagents).
• Production of biological response modifiers for study in preclinical and early-phase trials
  BRB’s oversight of the Biopharmaceutical Development Program (BDP; part of the Frederick National Laboratory for Cancer Research [FNLCR]) leads to the production of these modifiers. BRB leverages its grant portfolio to identify and shepherd extramural investigators’ drug products into the NCI Experimental Therapeutics (NExT) Program, which is an NCI mechanism that provides resources for drug discovery and development projects to extramural researchers. BRB manages a set of NExT projects that involves tasking the BDP to execute activities requiring close interaction, scientific guidance, and project management. BRB PDs also provide biologics development guidance to translational researchers through the NExT Program Consultation on Development of Experimental Cancer Drugs.

Dawn Edwards, Program Specialist
I’ve been working at NCI since the time of BRMP — 37 years total — all of which have been with BRB. I’ve had the honor to work with a talented group of scientists over the years in BRB, and some have moved on to become leaders in DTP and DCTD, including Drs. Aurigemma and Hecht, plus Dr. Creekmore, our previous branch chief who has since retired. I manage the administrative operations of this branch plus one other DTP branch, and I serve as back-up for six others. My responsibilities that relate to the daily operation of the branch include budget, acquisition, travel, training, personnel, organizational, and other administrative duties of the office.

Rachelle Salomon, PhD, Program Director
After eight years serving as a program officer for influenza research and development at NIAID, I joined BRB in 2017 to take on new challenges in drug development. BRB provides a unique opportunity to work closely with the BDP to develop new cancer therapies. Together we provide scientists with access to services and expertise in process development and analytics, GMP manufacturing, regulatory, and quality assurance. One thing I’ve learned during my time here is that lessons learned are important. As we expand our capabilities, we use previously acquired information when considering future projects. When we move into a new research area, it’s important to be mindful of what we learned along the way. This allows us to serve more people and take on more projects.

Jackie Smith, Program Specialist
I have been working at NCI since 2019. Dr. Salomon and I manage the repository of cytokines, monoclonal antibodies, and other biological reagents. We receive orders from investigators at universities worldwide, and we also receive orders within NIH. We look at the justification for their proposed work and send the order to Charles River Laboratories to request shipment of the reagents. In addition to our own tracking system, we have partnered with Charles River Laboratories to provide us with a monthly report of inventory. There are always orders coming in, so we need to keep track of the reagents that we send out to make sure we never run out. Oversight of the repository requires a lot of communication between BRB staff and the investigators requesting the repository’s reagents.

Cell Therapy Production
In 2018, BRB and the BDP began an initiative for cell therapy production at FNLCR. NCI now makes cell therapy products available to intramural and extramural clinical trial investigators. The timeline below describes the history of NCI’s recent capability in this area at FNLCR.

Fall 2018	BDP begins to develop CAR-T cell production capability
Summer 2019	First successful IND filing for BDP CAR-T clinical production for multisite clinical trial
January 2020	First clinical trial to administer BDP-manufactured CAR-T cells opens
March 2020	First patient enrolled on clinical trial receives BDP-manufactured CAR-T cells
Early 2021	Availability of cGMP lentivirus production using a scalable 4-plasmid production platform
Mid-2021	Availability of gamma retrovirus production
December 2021	G-Rex Platform added to BDP capabilities for cell therapy
March 2022	First patient enrolled on second clinical trial receives BDP-manufactured CAR-T cells
December 2022	BDP demonstrates ability to make CRISPR-based CAR-T cells
March 2023	Maximal tolerated dose (MTD) reached in the first CAR-T cell clinical trial after 24 patients treated; trial enters expansion phase
April 2023	BDP joins multi-site study on safety of pluripotent stem cells used in cell therapies

Ray Harris, PhD, Program Director
I supported BRB in the early 2000s as a contractor leading the virus development projects tasked to the BDP. In 2010, I went to work at NIAID, and then returned to DTP and BRB in 2019. While I was away, the Advanced Technology Research Facility (ATRF) at FNLCR was built. The ATRF is a well-designed research and development space that can support work with various types of biologics, including cell products. As a result of recent upgrades at the ATRF, our cell product manufacturing capacity will increase by 3-4-fold. Due to the varied nature of the projects tasked to the branch, we need staff with specialized skills and experience.

Kasia Bourcier, PhD, Program Director
I joined NCI in 2019 as a PD in DTP’s newly established ImmunoOncology Branch (IOB). I always had an interest in cell therapies, so when opportunity arose, I transferred to BRB in 2022. This work transition gave me an excellent opportunity to learn about the logistics of GMP manufacturing and to expand my technical knowledge about cell therapies. I am co-leading DTP’s efforts on the Cancer Adoptive Cellular Therapy Network (Can-ACT) funding opportunities for adult and pediatric solid cancers. Through this initiative BRB will support the development and clinical advancement of state-of-the art cell therapies for solid tumors. The Can-ACT management group is very collaborative, involving many staff with different expertise across DCTD. We are all looking forward to launching the Can-ACT network in a few months.

Robin Barnett, Program Specialist
I have been working at NCI for 35 years. I originally started with BRB in 2001 and then moved around in Frederick a bit working with Drs. Robert Shoemaker and Melinda Hollingshead. I have been back in BRB for 3 years now, and it is an immense pleasure to be working with Dr. Yovandich and his team of scientists. I provide comprehensive administrative and program support to six DTP branches related to personnel, travel, training, timekeeping, budget administration, branch procurement, property management, publication coordination, and other administrative duties. These are all important to keep the labs running smoothly. I also serve as a back-up for four other DTP branches.

Jayne Christen, PhD, PMP, Program Director
I came to BRB in 2022 from Leidos Biomedical’s Vaccine, Immunity, and Cancer Directorate. I immediately took over the management of Jason’s grant portfolio, and I also serve as a project scientist for a U01 award in CSSI’s Synthetic Biology and Cancer Program, and am a certified Contracting Officer Representative Level II (COR II). As the BRB lead, I manage a diverse portfolio of NExT Program projects that are focused on the development of novel biologics, including a recombinant protein for the treatment of breast cancer, an antibody-drug conjugate for treating T-cell lymphoma, a retroviral vector required for the production of a TCR T cell therapy, and an enzyme for the treatment of acute lymphoblastic leukemia. While each project will likely encounter unique challenges throughout the development lifecycle, I am excited to assist the project team in overcoming these challenges and to have a role in taking these biologics from the bench to the bedside.

New Areas of Translational Research
Synthetic biology, cellular engineering, and nanotechnology are newer areas for BRB. The branch is supporting a neo-antigen peptide vaccine clinical trial for pancreatic cancer treatment. Tumor sequencing and algorithmic-based probabilities for successful synthesis and immunological response identify the targeted mutations needed to manufacture this vaccine.

BRB has expertise in virus-engineered cell therapies but anticipates that the BDP will need CRISPR-based gene editing technologies and platforms for next-generation cell therapies. With the success of the lipid nanoparticle mRNA vaccines for COVID-19, the cancer vaccine field will explode with new concepts based on these platforms. These concepts mix chemistry, synthetic biology, nanotechnology, and biological manufacturing; therefore, BRB will need to collaborate closely with the Nanotechnology Characterization Laboratory and other groups across DCTD to shepherd these concepts into the clinic.

Mahnue Sahn, CRTA Fellow
I’ve been in BRB for 5 months as a CRTA fellow, and most of my work has been in cell therapy. I’m getting great experience working closely on cell therapy projects and seeing a lot of different techniques. I am gaining a foundational understanding for why the technology is being developed and why it’s essential for cell therapy. This research is more revolutionary than I realized. Even as a trainee, I am contributing, and this is the best part of my experience here. When I’m done working with BRB, I hope to use my skills in my next position.

Assistance to NIH and other federal agencies
In addition to executing DTP’s mission, BRB can help staff across NIH and the government through DCTD’s contract access to the FNLCR. Recently, BRB helped with an NCI/CCR viral vector for use in manufacturing a cell-therapy product. BRB also worked with NIAID on the development of vaccines for malaria and Epstein-Barr virus and with NCATS on gene therapy vectors for rare diseases. Staff in the FDA (CBER and CDER) have access to the BDP facility for training new product reviewers. BRB plays an important role in making sure that the resources for these projects are used appropriately and that the projects run as smoothly as possible. In the future, NCI may look to the BDP and FNLCR to help fill a critical need to provide technology and resources to the extramural translational community to develop mRNA vaccine therapies for a variety of diseases.

SPOTLIGHT: NCI Celebrates Black History Month

In celebration of Black History Month in February, NCI’s Divisions, Offices, and Centers participated in a Twitter social media event to highlight staff and their contributions to NCI’s mission. DCTD invited staff to participate in this NCI-wide observance, and the following DCTD staff were recognized on our division’s Twitter account, @NCITreament . Click on each person’s photo to see their DCTD Twitter post and what NCI’s mission means to them.

DCTD Diversity, Equity, Inclusion, and Accessibility (DEIA) Update

From Leah Hubbard, PhD, DCTD Program Director, DCTD Chief Diversity Officer

DCTD remains committed to ensuring DEIA in our workforce, hiring practices, and workplace culture. Since our January newsletter update, we have enhanced DEIA in our division by:

• Collaborating with the DCTD Administrative Resource Center (ARC) to develop new benchmark procedures to support staff individual training, professional development, and career advancement.
• Launching the DCTD DEIA webpage, which details our commitment to DEIA, NIH/NCI DEIA activities/resources, professional development resources, and opportunities for staff to provide feedback.

We also continue to make substantial efforts in the following areas:

• Collaborating with the NCI Equity and Inclusion Program Working Group 3 to develop an NCI hiring best practices toolkit/training as well as formal recommendations to improve operational efficiencies in the NCI hiring process.
• Convening regular DEIA meetings with DCTD leadership and the ARC to assess the workplace climate, evaluate recruitment/hiring procedures, identify areas for improvement, and create new programs.
• Broad and targeted outreach to underrepresented groups regarding all DCTD job openings.

NEWS ACROSS DCTD

Pragmatica-Lung Clinical Trial

The Pragmatica-Lung clinical trial launched in early March 2023. It is a unique clinical trial that is part of a broader NCI and FDA effort to modernize clinical trials. The hope is that this type of simplified trial can be less burdensome to patients and investigators and serve as a model for future cancer clinical trials. NCI is sponsoring the trial, and the SWOG Cancer Research Network is leading it in collaboration with the Alliance for Clinical Trials in Oncology. The study is being conducted with participation of the four US NCI National Clinical Trials Network (NCTN) groups that focus on cancer in adults. Pharmaceutical companies Merck and Eli Lilly and Co. are each providing one of the study drugs and additional trial funding. Pragmatica-Lung Study opens for patient enrollment — NCI Press Release

Inside Cancer Careers Podcast — Episode 2: Giving and Getting a Grant

Hear DCTD Program Director (PD) and Chief Diversity Officer, Leah Hubbard, PhD, in Episode 2 of Inside Cancer Careers, an NCI podcast that explores and illuminates the exciting world of cancer research training to bring a new generation of investigators into the field. Dr. Hubbard joined Dr. Eric Johnson Chavarria, a PD in the Division of Cancer Biology to discuss their career journeys and Dr. Dianna Ng, a K08 awardee and pathologist at Memorial Sloan Kettering Cancer Center in this podcast. The NCI Center for Cancer Training leads the podcast, which aims to uncover emerging trends and technologies in cancer research, examine how researchers can succeed in a high-pressure and competitive environment, and delve into the importance of diversity, equity, inclusion, and accessibility in the workplace.

United States-Republic of Korea (ROK) Collaboration

Since 2016, the ROK has participated in a research effort that is aligned with the Cancer Moonshot — the NCI International Cancer Proteogenome Consortium (ICPC). The ROK’s participating institutes are the National Cancer Center Korea, Korea Institute of Science and Technology, Korea University, Daegu Gyeongbuk Institute of Science and Technology, and Kyung Hee University. In the ICPC, the ROK focuses research on eight cancer types affecting their population and contributes to an improved understanding of gastric and pancreatic cancer through proteogenomics. The resulting data are available to the global cancer research community on the Office of Cancer Clinical Proteomics Research website.

Over the last five years, NCI has supported 75 collaborations with ROK investigators and institutions involving many cancer types and areas of cancer research. With a shared interest in expanding these collaborations, on April 26, 2023, NCI and the National Cancer Center Korea signed a new Memorandum of Understanding (MOU). Under the latest MOU, the collaborations will include cancer proteogenomics plus research related to cancer prevention, early diagnosis, treatment, and management of cancer survivors. Read the NCI Center for Global Health’s blog about the MOU.

DCTD-supported Research at the 2023 Annual Meeting of the American Association for Cancer Research (AACR)

DCTD staff and extramural investigators presented DCTD-supported research at AACR this year. See all the presentations that included DCTD staff co-authors in tables listing the oral, poster, and meet-the-expert sessions.

NIH Cancer, Aging, and Comorbidities Webinar Series

There is still time to attend two webinars in this seven-part series:

• June 15 — Food as a Drug
• July 14 — Senescence, Cancer, Treatment-Associated Accelerated Aging, and Comorbidities

Register for the webinar series.
Contact: Weiwei Chen, PhD (chenw6@mail.nih.gov)

Second NCI Drug Development Workshop

Register for the second NCI Drug Development Workshop, which will be held on three sets of Thursdays/Fridays from June 22 — July 28, 2023, starting at 1:00 pm ET.

The Developmental Therapeutics Program is leading this educational workshop that follows their first webinar series entitled “NCI Drug Development Workshop: How to Advance a Therapeutic Candidate from Bench to Bedside.” This second workshop will address specialized topics that are important for the preclinical development of small molecule cancer drugs. Speakers will be from government, academia, and industry.

Contacts: Weiwei Chen, PhD (chenw6@mail.nih.gov) and Sundar Venkatachalam, PhD (sundar.venkatachalam@nih.gov).

Staff in the Cancer Imaging Program’s Molecular Imaging Branch to Host Session in the 2023 World Molecular Imaging Congress

Pushpa Tandon, PhD, Yisong Wang, PhD, Charles Lin, PhD, and Chiayeng Wang, PhD, organized a Spotlight Session that will be held at the upcoming World Molecular Imaging Congress .

Title: Targeting the altered microenvironment and premalignant niches to prevent metastatic disease
Date/Time: September 7, 2023; 4:30 pm-6:00 pm

New on DCTD Websites

Guidance for Program Project Grants

DCTD recently posted guidance for extramural investigators interested in applying for Program Project Grants (P01). The goal of this guidance is to help investigators navigate through the P01 pre-application process in the cancer research areas that DCTD supports.

Diversity, Equity, Inclusion, and Accessibility (DEIA) in DCTD

DCTD is committed to ensuring DEIA in our workforce and providing a safe work environment for our staff. We are pleased to announce a new DCTD webpage dedicated to our DEIA efforts within the division.

Our new webpage provides DEIA resources for staff and the public plus information on DCTD’s four areas of commitment to DEIA:

• Inclusion
• A Safe Workplace
• DEIA in Recruitment and Hiring
• Accountability

DCTD Career Opportunities

DCTD just launched a DCTD Careers page, which provides information on DCTD’s job opportunities before the official vacancy announcements are available on USAJobs.com. Interested individuals are encouraged to create a USAJobs account and to set up notifications in anticipation of vacancy postings. Points-of-contact are listed for the individual job descriptions.

Selected Recent Publications and NCI Cancer Currents Blog Posts

Publications

Martinez-Fructoso L, Arends SJR, Freire VF, et al. Screen for new antimicrobial natural products from the NCI Program for Natural Product Discovery Prefractionated Extract Library. ACS Infect Dis. 2023 May 10. Online ahead of print. PubMed

Greytak SR, Engel KB, Hoon DSB, et al. Evidence-based procedures to improve the reliability of circulating miRNA biomarker assays. Clin Chem Lab Med. 2023 May 3. Online ahead of print. PubMed

Gross AM, Dombi E, Wolters PL, et al. Long-term safety and efficacy of selumetinib in children with neurofibromatosis type 1 on a phase 1/2 trial for inoperable plexiform neurofibromatosis. Neuro Oncol. 2023 Apr 28. Online ahead of print. PubMed

Clark AS, Hong F, Finn RS, et al. Phase II study of Palbociclib (PD-0332991) in CCND1, 2, or 3 amplification: Results from the NCI-MATCH ECOG-ACRIN Trial (EAY131) subprotocol Z1B. Clin Cancer Res. 2023 Apr 14;29(8): 1477-1483. PubMed

Meric-Bernstam F, Ford JM, O’Dwyer PJ, et al. National Cancer Institute Combination Therapy Platform Trial with Molecular Analysis for Therapy Choice (ComboMATCH). Clin Cancer Res. 2023 Apr 14;29(8):1412-1422. PubMed

Kantor O, King TA, Freedman RA, et al. Racial and ethnic disparities in locoregional recurrence among patients with hormone receptor-positive, node-negative breast cancer: A post hoc analysis of the TAILORx randomized clinical trial. JAMA Surg. 2023 Apr 12. Online ahead of print. PubMed

Laranjeira ABA, Hollingshead MG, Nguyen D, et al. DNA damage, demethylation and anticancer activity of DNA methyltransferase (DNMT) inhibitors. Sci Rep. 2023 Apr 12;13(1):5964. PubMed

Dubois SG, Krailo MD, Glade-Bender J, et al. Randomized phase III trial of ganitumab with interval-compressed chemotherapy for patients with newly diagnosed metastatic ewing sarcoma: A report from the Children’s Oncology Group. J Clin Oncol. 2023 Apr 10;41(11):2098-2107. PubMed

Nguyen J, Takebe, N, Kummar S, et al. Randomized phase II trial of sunitinib or cediranib in alveolar soft part sarcoma. Clin Cancer Res. 2023 Apr 3;29(7):1200-1208. PubMed

Wisinski KB, Flamand Y, Wilson MA, et al. Trametinib in patients with NF1-, GNAQ-, or GNA11- mutant tumors: Results from the NCI-MATCH ECOG-ACRIN trial (EAY131) subprotocols S1 and S2. JCO Precis Oncol. 2023 Apr;7e2200421. PubMed

Evans JR, Akee RK, Chanana S, et al. National Cancer Institute (NCI) Program for Natural Product Discovery: Exploring NCI-60 screening data of natural product samples with artificial neural networks. ACS Omega. 2023 Mar 1;8(10):9250-9256. PubMed

Shankar LK, Schoder H, Sharon E, et al. Harnessing imaging tools to guide immunotherapy trials: summary from the National Cancer Institute Cancer Imaging Steering Committee workshop. Lancet Oncol. 2023 Mar;24(3)e133-e143. PubMed

Forry S, Hubbard L, Espey MG, et al. The NCI Glioblastoma Therapeutics Network (GTN). Neuro Oncol. 2023 Feb 14;25(2):221-223. PubMed

Huang EP, O’Connor JPB, McShane LM, et al. Criteria for the translation of radiomics into clinically useful tests. Nat Rev Clin Oncol. 2023 Feb;20(2):69-82. PubMed

Best AF, Bowman M, Li J, et al. COVID-19 severity by vaccination status in the NCI COVID-19 and Cancer Patients Study (NCCAPS). J Natl Cancer Inst. 2023 Jan 25. Online ahead of print. PubMed

Freidlin B and Korn EL. Augmenting randomized clinical trial data with historical control data: Precision medicine applications. J Natl Cancer Inst. 2023 Jan 10;115(1):14-20. PubMed

Baranda JC, Diaz FJ, Rubinstein L, et al. Expanding access to early phase trials: the CATCH-UP.2020 experience. JNCI Cancer Spectr. 2023 Jan 3;7(1):pkac087. PubMed

Sankaran H, Finnigan SR, McShane LM, et al. Enrollment of adolescent and adult patients newly diagnosed with cancer in NCI CTEP-sponsored clinical trials before and after launch of the NCI National Clinical Trials Network. Cancer. 2022 Nov 1;128(21):3843-3849. PubMed

NCI Cancer Currents Blogs

Rare melanoma very likely to respond to treatment with pembrolizumab

Nirogacestat may offer hope to people with desmoid tumors

Transforming cancer clinical trials for better, faster results

Immunotherapy role in treating endometrial cancer expected to grow

Liquid biopsies on the horizon for children with solid cancers

Strategies may prevent tumor resistance to targeted cancer therapies

Dexrazoxane protects the heart long term for kids being treated for cancer

Tucatinib and trastuzumab combination approved for advanced colorectal cancer

Trial suggests expanded role for blinatumomab in treating ALL

FUNDING UPDATES

Title	Announcement Number	Important Dates	Activity Code
Notice of Intent to Publish a Funding Opportunity Announcement for Mechanisms of Fusion-Driven Oncogenesis in Childhood Cancers (Clinical Trial Not Allowed)	NOT-CA-23-057	Estimated to be available November 17, 2023	U01
Notice of Intent to Publish a Funding Opportunity for Next Generation Chemistry Centers for Fusion Oncoproteins (Clinical Trial Not Allowed)	NOT-CA-23-058	Estimated to be available November 17, 2023	UM1
Notice of Special Interest (NOSI): Administrative Supplements for the Dog Oncology Grant Supplement (DOGS) Program	NOT-CA-23-059	First due date: June 15, 2023 Closes: June 16, 2023	Admin Suppl
Request for Information: Seeking input for NCI Cancer Adoptive Cellular Therapy (Can-ACT) Network on Clinical Trials Data Planning and Sharing	NOT-CA-23-042	Response Date: June 12, 2023