director’s message

Greetings!

I would like to start by expressing gratitude to you, the immuno-oncology (IO) community, for your hard work and dedication. Thank you for your participation in the Pelotonia Institute for Immuno-Oncology (PIIO) Symposium on Nov. 2. Special thanks to our seminar speakers—Drs. Antoni Ribas (president, American Association for Cancer Research), David Carbone (OSUCCC – James), Christian Jobin (University of Florida), Elaine Mardis (Nationwide Children’s Hospital), Miriam Merad (Mount Sinai School of Medicine), Eugene Oltz (OSUCCC – James) and Cassian Yee (The University of Texas MD Anderson Cancer Center)—and to everyone who presented their research at the poster session. Your participation enhanced the meeting, and we look forward to your attendance and interaction in 2021. View a recording of the symposium.

On Nov. 9, we participated in a site visit of the new Interdisciplinary Research Facility (IRF), which is being built on West Campus and is slated for completion in the summer of 2023. As you may know, two floors of the IRF will be dedicated to The Ohio State University Comprehensive Cancer Center, including space for the PIIO. Ample space for the institute will be crucial as we work toward being a leader in driving IO breakthroughs. Building stellar programs is also a critical component of reaching our goals. In partnership with the Department of Microbial Infection and Immunity, we are establishing a master’s program in Immunity and Microbial Pathogenesis (Fall 2021). We are deepening our partnership with Nationwide Children’s Hospital with expansion of cell therapy, and we are developing a strategic plan for cell therapy in partnership with Ohio State’s Cell Therapy Program. We also are developing translational IO biorepository programs linked to bioinformatics in partnership with the Translational Therapeutics Program and the Department of Biomedical Informatics. And we are continuing to build an Immune Monitoring and Discovery Platform (IMDP) as a technological hub for innovative research. More detailed IMDP updates have been provided in this newsletter by IMDP Associate Director Kevin Weller. With regard to recruitment, the PIIO Search Committee has been established with an emphasis on recruiting senior candidates to lead the PIIO’s Centers of Research Excellence.

In light of the recent Thanksgiving holiday, the upcoming holidays and the promise of a new calendar year, we have much to be thankful for. News on the COVID-19 vaccine front is promising. However, with news of spiking cases in our state and across the nation, and with hospital ICUs nearing maximum capacity, we still have much work to do to combat this deadly pandemic. We must continue to be vigilant with wearing our masks properly in public, with regular hand washing and with physical distancing. We can bring the COVID numbers down, but each of us must do the right things in the right way!

Sincerely,

Zihai

Zihai Li, MD, PhD
Klotz Memorial Chair in Cancer Research
Professor and Founding Director
Pelotonia Institute for Immuno-Oncology

UPDATE: THE IMMUNE MONITORING & DISCOVERY PLATFORM (IMDP)

The IMDP lab is growing again, and in more ways than one. The IMDP welcomed Lab Manager Jamie Hamon to our team over the summer. Hamon has an MS in molecular genetics from Ohio State. Her work experience includes serving as a cell therapy process development laboratory specialist here, and as a project leader and master technician at Battelle Biomedical Research Center. We are also welcoming Dr. Komal Das as our senior imaging specialist. Dr. Das has a PhD in biomedical sciences from Ohio State and more than 10 years of biomedical sciences and engineering experience.

The IMDP has also been expanding its technological resources to provide additional cutting-edge technology for our members. In our previous newsletter, the IMPD reported that the Cytek Aurora Spectral Flow Cytometer had been upgraded and that a Fuidigm Melio Mass Cytometer had been installed, joining the 10X Genomics Chromium instruments and the Isoplexis Isolight. Installation and training are being finalized for:

• Akoya Vectra Polaris Digital Imaging Platform, a fully automated, high-throughput system providing state-of-the-art multispectral imaging that enables identification and downstream quantification of up to eight overlapping biomarkers. This technology generates unmixed whole slide scans at 40x magnification of up to seven colors for analysis across the entire slide without selection bias;

• Eppendorf epMotion 5070, an automated system providing high-performance, extremely precise pipetting that will be utilized for series dilutions, dispensing reagents, transferring samples and standardizing samples. By adding this system, the IMDP will standardize and automate pipetting while better utilizing IMDP staff in the lab;

• System 9 Agilent 4150 TapeStation, which utilizes established ScreenTape technology for ease of use running 16 samples in less than 20 minutes and providing a wide range of RNA and DNA ScreenTape applications, including assays for genomic and cell-free DNA;

• Cytek Northern Lights Spectral Analyzer, the only full-spectrum unmixing flow cytometer with three lasers, 38 FL APD detectors, vacuum fluidics, small-particle detection and a capability of 27+ colors. By adding this system, the IMDP can stratify users by experimental complexity need, doubling capacity without doubling costs (many users don’t require the full power of the Aurora instrument);

• BD FACS Melody Cell Sorter, an instrument capable of sorting four ways with up to nine fluorescent colors into tubes or plates. It has multiple nozzles that are sized to allow user customization for a variety of cell types. All start-up, cleaning and shutdown procedures are automated;

• gentleMACS Dissociator, an instrument that has an optimized, pre-set program for easy dissociation of tissues into single-cell suspensions, including: mouse or human tumor; mouse or rat neonatal heart; neural tissue; mouse spleen/lung/lamina propria/muscle/epidermis/liver; mouse or human skin; and more. It also has optimized programs for thorough homogenates, including: total RNA or mRNA isolation from fresh or frozen samples; protein extraction; determination of bacterial or viral load; and mitochondria isolation. The gentleMACS provides reliable and reproducible results in a closed system;

• EVOS 7000 Multiplex IHC Imager, which provides powerful image analysis capabilities for cell segmentation and quantification, along with fully integrated time-lapse live-cell imaging, high-speed image acquisition, and multi-position well scanning. It provides outstanding image quality and versatility with a five-position objective turret, four-color LED fluorescence and transmitted light channels, and 3.2 MP CMOS color and black-and-white cameras.

piio wins!

A study led by the laboratory of Thomas Mace, PhD, revealed a mechanism for CD200 expression in the pancreatic tumor microenvironment (TME) to promote immunosuppression. This research by Fouad Choueiry et al. discovered the elevated expression levels of CD200 in the pancreatic TME and increased expression of the receptor (CD200R) by myeloid-derived suppressor cells (MDSC) in patients. Antibody blockade of CD200 in preclinical animal models of pancreatic cancer was found to limit tumor growth, reduce intratumoral MDSC and enhance checkpoint blockade immunotherapy. The group also provided evidence that CD200 can enhance the differentiation and suppressive activity of MDSC. These findings were recently reported in theJournal for the Immunotherapy of Cancer (JITC).

The Ohio State University Corporate Engagement Office granted Zhiwei Hu, PhD, MD, and his team an Accelerator Award for their project titled “Targeting Pathological Neovasculature for Treatment of Advanced Triple-Negative Breast Cancer (TNBC) Using Tissue Factor-Recognizing Chimeric Antigen Receptor (CAR)-Engineered Natural Killer and T Cells.” The technology, specific to a new target in TNBC, may prevent recurrences and have fewer side effects than current treatments. Accelerator Award funds will be used to investigate the efficacy and safety of the technology in preclinical animal studies, with the goal of commercializing it for treating patients with TNBC. Hu’s team includes John MacDonald, MBA, PhD;  Rong An, PhD; Allan Tsung, MD; Rulong Shen, MD; and Chengli Shen, MD, PhD.    

Congratulations to Ephraim Ansa-Addo, PhD, and Zihai Li, MD, PhD, for their recent publication in Science Advances. The article, titled “RNA Binding Protein PCBP1 is an Intracellular Immune Checkpoint for Shaping T-Cell Responses in Cancer Immunity,” demonstrates a critical role for PCBP1 as an intracellular immune checkpoint for maintaining Teff cell functions in cancer immunity. Ansa-Addo’s lab seeks to define how cellular and molecular regulators determine the functions of Tregs in the tumor microenvironment and to use these insights to leverage current treatment approaches in cancer immunotherapy. Learn more about this study.

The laboratory of Zihai Li, MD, PhD, is participating in the OncoImmune Phase III clinical trial of CD24Fc to treat patients hospitalized with COVID-19. The novel coronavirus SARS-CoV-2 causes inflammation that worsens clinical symptoms. CD24Fc is a first-in-class biologic that fortifies an innate immune checkpoint against excessive inflammation caused by tissue injuries. In this new double-blind, randomized, multicenter, phase III trial, CD24Fc safety and efficacy will be assessed in about 230 patients exhibiting severe clinical symptoms. Special thanks to Carlos Malvestutto, MD, MPH (study PI), Donna Bucci, Hakan Cam, PhD, Karthik Chakravarthy, Ezgi Elmas, Teresa Kutcher, Kelsi Reynolds (clinical trials associate), Brian Riesenberg, PhD, No Joon Song, PhD, and Mohamed Yusuf for their diligence in this very important project.

NEW GRADUATE COURSES BEING OFFERED

FUNDAMENTALS OF ONCOLOGY: PATHOL 6640

We will be resuming this four-credit-hour course in the spring of 2021. It will be 100% online and will consist of lectures/seminars covering various subjects and recent advances in oncology. Lectures will be provided by leading experts in the field. Reading will be from primary sources in current scientific literature. Seminars will be interactive and will encourage critical evaluation of the reading assignments.
Course coordinators: Steve Oghumu, PhD, and Anna Vilgelm, MD, PhD
Class Meeting Schedule: Synchronous sessions regularly meeting via CarmenZoom: Tuesdays and Thursdays, 2-4 p.m.

Course Learning Outcomes: By the end of this course, students should be able to: appreciate key aspects of the cancer biology research field; explain distinct features of multiple cancer types; describe genetics of cancer initiation; understand the role of environmental factors in cancer initiation; communicate the role of epigenetic regulation, miRNA, transcription regulation and growth factors/hormone signaling in cancer progression; explain molecular mechanisms that drive cancer progression; describe the role of tumor stroma in cancer progression; understand the importance of clinical research and patient materials; appreciate the role of omics technologies in the advancement of cancer research; understand the tumor immune microenvironment and the roles of different immune cell types in cancer progression; explain the mechanisms of tumor immune evasion; describe innovative technologies that enable researchers and clinicians to gain a comprehensive understanding of tumor-immune interplay; communicate diverse cancer treatment options, including innovative approaches such as precision medicine and immunotherapy; explain key steps of cancer drug discovery; identify fast-advancing fields and promising emerging topics in basic and translational cancer research.

CANCER IMMUNOLOGY: CRITICAL JOURNAL READINGS BSGP 7900  

Semester: Spring 2021 
Time: Tuesdays, 10-11 a.m. 
Location: Via Zoom and in Graves Hall 1165 
Credits: 1
(Syllabus attached) 

BSGP 7900 is a journal club in which students and postdoctoral fellows give critical interpretations of research and journal readings on cancer immunology. Participants will lead discussion and critically examine recent cutting-edge literature in the field of tumor immunology. They also will 1) broaden their understanding of current trends in cancer immunology research, 2) enhance their ability to analyze the theory, methods and significance of peer-reviewed articles from the primary literature, and 3) improve their presentation skills and ability to participate in discussion of the primary literature. This course will most likely begin as a 100% online course and may later transition to a hybrid course. Participation is synchronous (live), and participants will be required to log into CarmenZoom once a week during the appointed class time. A Zoom link for this class will be emailed to all students prior to the semester. 

Registration for class credit is not required. Postdoctoral fellows and students interested in attending without class credit should email Thomas Mace, PhD. Students are welcome to repeat this class if they attended it during a previous semester. For further information, contact Dr. Mace.

NEW IMMUNOTHERAPY AGENTS AND/OR INDICATIONS APPROVED BY THE FDA

• Naxitamab (DANYELZA, Y-mAbs Therapeutics, Inc.) in combination with granulocyte-macrophage colony-stimulating factor (GM-CSF): For pediatric patients one year of age and older, and adult patients with relapsed or refractory high-risk neuroblastoma in the bone or bone marrow demonstrating a partial response, minor response or stable disease to prior therapy.

• Pembrolizumab (KEYTRUDA, Merck & Co.) in combination with chemotherapy: Accelerated approval given for the treatment of patients with locally recurrent unresectable or metastatic triple-negative breast cancer (TNBC) whose tumors express PD-L1 (CPS ≥10) as determined by an FDA-approved test.

• Carfilzomib (KYPROLIS, Onyx Pharmaceuticals, Inc.) and Daratumumab (DARZALEX, Janssen Biotech, Inc.): For adult patients with relapsed or refractory multiple myeloma who have received one to three lines of therapy.

• Azacitidine Tablets (ONUREG®, Celgene Corporation): For continued treatment of patients with acute myeloid leukemia who achieved first complete remission (CR) or complete remission with incomplete blood count recovery (CRi) following intensive induction chemotherapy and are not able to complete intensive curative therapy.

• Nivolumab and Ipilimumab (OPDIVO and YERVOY, Bristol-Myers Squibb Co.): Combined nivolumab (anti-PD-1) and ipilimumab (anti-CTLA-4) as first-line treatment for adult patients with unresectable malignant pleural mesothelioma.

Publications

NOTE: OSUCCC members are denoted in bold, and the abbreviations of their respective research programs are indicated in parentheses. The abbreviations for programs listed below are: LR (Leukemia Research), TT (Translational Therapeutics) CB (Cancer Biology) and CC (Cancer Control).

Ansa-Addo E (TT), Huang HC, Riesenberg B, Iamsawat S, Borucki D, Nelson MH, Nam JH, Chung D (ROI), Paulos CM, Liu B (LR), Yu XZ, Philpott C, Howe PH, Li Z (TT). RNA binding protein PCBP1 is an intracellular immune checkpoint for shaping T cell responses in cancer immunity. Science Advances 2020 May; 29;6(22):eaaz3865. doi: 10.1126/sciadv.aaz3865. pubmed: 32523987 

Owen DH (TT), Benner B, Pilcher C, Good L, Savardekar H, Norman R, Ghattas C, Shah
M (TT), Konda B, Verschraegen CF (TT), Wesolowski R (TT), Behbehani GK (LR), Carson WE (TT), Otterson GA. Deep and durable response to nivolumab and temozolomide in small-cell lung cancer associated with an early decrease in myeloid-derived suppressor cells. Clinical Lung Cancer 2020 November; 2:S1525-7304(20)30328-4. doi: 10.1016/j.cllc.2020.10.018. Epub ahead of print. pubmed: 33234490

Khountham S, Shindiapina P, Mo X, Lachowiez C, Wiczer T, Mousa L, Rogers KA (LR),
Andritsos LA, Woyach JA (LR), Byrd JC (LR), Spurgeon SE, Awan FT. Natural history of noninfectious, ibrutinib-attributable adverse events in patients with chronic lymphocytic leukemia. Leukemia & Lymphoma 2020 November; 19:1-6. doi: 10.1080/10428194.2020.1838508. Epub ahead of print. pubmed: 33210562

Patel JD, Lee JW, Carbone DP (TT), Wagner H, Shanker A, de Aquino MTP, Horn L,
Johnson ML, Gerber DE, Liu JJ, Das MS, Al-Nsour MA, Dakhil CSR, Ramalingam S,
Schiller JH. Phase II study of immunotherapy with tecemotide and bevacizumab
after chemoradiation in patients with unresectable stage III non-squamous non-
small-cell lung cancer (NS-NSCLC): a trial of the ECOG-ACRIN Cancer Research
Group (E6508). Clinical Lung Cancer 2020 November; 21(6):520-526. doi: 10.1016/j.cllc.2020.06.007. Epub 2020 June 12. pubmed: 32807654; PMCID: PMC7606595

Lipschitz N, Earl BR, Cripe TP (TT), Samy RN. Oncolytic virotherapy: a potential
therapeutic approach for cholesteatoma. Current Opinion in Otolaryngology & Head and Neck Surgery 2020 October; 28(5):281-285. doi: 10.1097/MOO.0000000000000651. pubmed: 32833886

Nalin AP, Kowalski JJ, Sprague AC, Schumacher BK, Gerhardt AG, Youssef Y,
Vedantam KV, Zhang X, Siebel CW, Mace EM, Caligiuri MA, Mundy-Bosse BL (LR), Freud
AG (LR). Notch regulates innate lymphoid cell plasticity during human NK cell
development. Journal of Immunology 2020 November; 15;205(10):2679-2693. doi:10.4049/jimmunol.2000434. Epub 2020 Oct. 5. pubmed: 33020148; PMCID: PMC7658047

Naeimi Kararoudi M, Nagai Y, Elmas E, de Souza Fernandes Pereira M, Ali SA,
Imus PH, Wethington D, Borrello IM, Lee DA (LR), Ghiaur G. CD38 deletion of human
primary NK cells eliminates daratumumab-induced fratricide and boosts their
effector activity. Blood 2020 November; 19;136(21):2416-2427. doi: 10.1182/blood.2020006200. pubmed: 32603414

Avenarius MR, Miller CR, Arnold MA, Koo S, Roberts R, Hobby M, Grossman T,
Moyer Y, Wilson RK, Mardis ER (TT), Gastier-Foster JM, Pfau RB. Genetic
characterization of pediatric sarcomas by targeted RNA sequencing. Journal of Molecular Diagnostics 2020 October; 22(10):1238-1245. doi: 10.1016/j.jmoldx.2020.07.004. Epub 2020 Aug 1. pubmed: 32745614 PMCID: PMC7538815

Jones DM, Read KA, Oestreich KJ (CB). Dynamic roles for IL-2-STAT5 signaling in
effector and regulatory CD4+ T-cell populations. Journal of Immunology 2020 October;
1;205(7):1721-1730. doi: 10.4049/jimmunol.2000612. pubmed: 32958706

Shankar B, Zhang J, Naqash AR, Forde PM, Feliciano JL, Marrone KA, Ettinger DS, Hann CL, Brahmer JR, Ricciuti B, Owen D (TT), Toi Y, Walker P, Otterson GA (TT), Patel SH, Sugawara S, Naidoo J. Multisystem immune-related adverse events associated with immune checkpoint inhibitors for treatment of non-small cell lung cancer. JAMA Oncology 2020 October (Epub ahead of print) pubmed: 33119034; PMCID: PMC7596677

Richmond A, Yang J, Yan C, Vilgelm AE (TT), Chen SC, Ayers GD, Johnson CA. Targeted deletion of CXCR2 in myeloid cells alters the tumor immune environment to improve antitumor immunity. Cancer Immunology Research 2020 November (Epub ahead pf print). pubmed: 33177110

Joshi M, Grivas P, Mortazavi A (MCC), Monk P, Clinton SK (MCC), Sue-Ann Woo M, Holder SL, Drabick JJ, Yin M. Alterations of DNA damage response genes correlate with response and overall survival in anti-PD-1/PD-L1-treated advanced urothelial cancer. Cancer Medicine 2020 October (Epub ahead of print). pubmed: 33098265

Shukuya T, Ghai V, Amann JM, Okimoto T, Shilo K, Kim TK, Wang K, Carbone DP (TT). Circulating miRNAs and extracellular vesicle-containing miRNAs as response biomarkers of anti-PD-1/PD-L1 therapy in non-small-cell lung cancer. Journal of Thoracic Oncology 2020; Epub June: pubmed: 32565389

Li M, Spakowicz D (MCC), Zhao S, Patel SH, Johns A, Grogan M, Miah A, Husain M, He K (TT), Bertino EM (TT), Shields PG (CC), Wei L, Carbone DP (TT), Otterson GA (TT), Presley CJ (CC), Owen DH (TT). Brief report: inhaled corticosteroid use and the risk of checkpoint inhibitor pneumonitis in patients with advanced cancer. Cancer Immunology, Immunotherapy 2020; Epub July: pubmed: 32728772