The ISSNAF Young Investigator Paola Campese Award for Research in Hematologic Malignancies was established by Stefania and Vito Campese in 2011 in memory of their young, talented and generous daughter Paola.
Warmest congratulations to the outstanding finalists of the 2023 edition: Guido Ghilardi, Elisa Mandato, and Eugenio Morelli.
The finalists presented their exciting and innovative research at the Symposium on October 17, 2023 to the Jury chaired by Prof. Riccardo Dalla-Favera. Watch them in action: https://youtu.be/SSX56K-U9GM?si=LTsb0RVsrr5sbGxd
The Award winner will be announced at ISSNAF 2023 Annual Event on November 8.
Guido is an Italian physician-scientist who graduated from the Universita’ del Piemonte Orientale (Novara, Italy) and trained as a hematologist at the Oncology Institute of Southern Switzerland, a world-renowned center for the treatment of lymphomas, interested in adoptive immunotherapy, such as chimeric antigen receptor T cells (CART) immunotherapy. To study the mechanisms underlying resistance and toxicities of CART immunotherapy, Guido joined the Ruella’s laboratory at the Center for Cellular Immunotherapies at the University of Pennsylvania in 2020, where he works as a 4th year post-doctoral researcher.
The focus of Guido’s research is to improve CART immunotherapy in non-Hodgkin lymphomas by studying the causes of resistance and the mechanisms underlying CART toxicities to design innovative and safer therapeutic approaches. Guido’s main focus is studying how different lymphodepletion regimens are able to generate different cytokine and metabolite environments by the time of CART infusion, and how these modifications contribute to the emergence of toxicities and ultimately propose safer lymphodepletion regimens. Moreover, Guido is evaluating new approaches to overcome resistance to CART immunotherapy by designing a new optimized dual CART product able to prevent the emergence of antigen-negative escape.
The majority of lymphoma patients treated with CART19 relapse or experience severe toxicities. The recipient pre-infusion status, product characteristics, and tumor-related resistant mechanisms are features determining the outcome of CART19. The goal of my research is to study the key factors associated with limited response to CART19 or with toxicities to rationally design the next generation cellular immunotherapies. In particular, I studied:
Lymphodepletion regimens before CART19: I am studying how different lymphodepletion regimens modify cytokine and metabolite environment, ultimately affecting CART cells’ ability to engraft and expand once infused. I discovered that lymphodepletion directly contributes to the pathogenesis of CART toxicities. My research demonstrated that milder lymphodepletion regimens result in reduced toxicities and should therefore be encouraged in clinical practice.
Impact of impaired gut microbiota composition in CART19: I demonstrated that patients exposed to gut microbiota-damaging antibiotics within the 30 days preceding CART19 infusion responded poorly to treatment.
CD19-negative escape after CART19. Selection of CD19-negative resistant clones is a primary relapse mechanism after CART19. To prevent this phenomenon, I am evaluating, in vitro and in vivo, a new dual-CART targeting two distinct antigens on the tumor cell surface. This dual-CART product will ultimately be evaluated in a phase I clinical trial.
I am an Italian physician trained in hematology, currently post-doctoral researcher at the University of Pennsylvania.
My research focuses on understanding the factors affecting CART immunotherapy for lymphoma patients and designing new strategies to ameliorate it. My studies resulted in several milestone publications and awards. My translational research impacted clinical practice and brought us closer to developing safer and more effective treatments.
My long-term plan is to become an independent physician-scientist focused on advancing lymphoma immunotherapy. Being awarded with the Paola Campese ISSNAF Young Investigator Award would give me the honor of representing the Italian scientific excellence in North America.
I received my bachelor’s and master’s degree in Molecular Biology and Medical Biology, respectively, and completed my PhD in Onco-Hematology at the University of Padova, Italy. I joined the Medical Oncology Department at Dana-Farber Cancer institute (DFCI) in Boston, MA, to complete my postdoctoral training in the Division of Hematologic Neoplasia, Shipp lab. Last year, I joined the junior faculty at DFCI and Harvard Medical School as an Instructor in Medicine. My research interests include the investigation of mechanisms of immune escape and aberrant signaling pathways in aggressive B-cell lymphomas. My studies focus on identifying novel targetable vulnerabilities to increase the response to therapy in diffuse large B-cell lymphomas, using the recently developed genetic framework and considering the concurrent alterations in clinically relevant disease subsets. My postdoctoral research was funded by a Grant from the Lymphoma Research Foundation. I have a record of productive research studies published in international peer-reviewed journals, including Blood and Frontiers in Immunology. Additionally, I have presented my work in several international venues including the American Society of Hematology annual meeting and the American Association for Cancer Research meeting on Advances in Malignant Lymphoma.
Diffuse large B cell lymphoma (DLBCL) is an aggressive and heterogeneous hematologic malignancy. Our group has previously defined the genetic signatures of newly diagnosed DLBCLs and identified targetable vulnerabilities in specific subsets of tumors termed ‘Clusters’. Cluster 5 is a subset of poor-prognosis tumors with frequent MYD88L265P and CD79BY196X mutations. My studies revealed the role of MYD88L265P in augmenting proximal BCR signaling via DOCK8. DOCK8 depletion selectively decreases BCR signaling, proliferation and viability of DLBCLs with MYD88L265P and CD79BY196X mutations and increases the efficacy of BTK inhibition. Cluster 1 is characterized by BCL6 alterations often concurrent with inactivating mutations of CD70. CD70 is expressed by certain malignant B cells and the interaction with its receptor, CD27, induces T-cell activation and expansion. My research showed that mice with both Bcl6 and Cd70 genetic alterations develop more lymphomas starting at an earlier age as compared to mice with only Bcl6 alterations. Single-cell RNA sequencing analyses of cytotoxic CD8 and CD4 T cells suggest that the anti-tumor response is less effective and fails earlier in the absence of CD70/CD27 co-stimulation. Our findings have translational potential in DLBCL subsets with a specific combination of genetic alterations and inform the development of next-generation targeted therapies.
I am passionately committed to the translation of fundamental insights regarding the genetic and immunologic heterogeneity in defined lymphoid malignancies to the development of more effective therapies for patients in need. Having received training both in Italy and the US, my expertise as a molecular biologist and immunologist in laboratories with a profound understanding of the biology of lymphoid malignancies sets me up to achieve this goal.
I genuinely enjoy teaching students and I am committed to mentoring and supporting early career researchers, thus contributing to the future legacy of neuroimmunologists.
Eugenio is a hematologist-oncologist fully committed to basic and translational cancer research. He currently works as Lead Scientist at Dana-Farber Cancer Institute and is a Research Associate at Harvard Medical School (Boston, MA, USA).
Eugenio received his medical degree at Magna Græcia University, Catanzaro, Italy in 2011. He completed his specialty in Medical Oncology at Magna Græcia University, Catanzaro, Italy in 2017. Afterward, he joined Dana-Farber Cancer Institute as a research fellow and then instructor and lead scientist.
His long-term research interest is to decode the key oncogenic features of noncoding RNAs to unlock their therapeutic potential, with a focus on blood cancers, particularly multiple myeloma. As such, he has deeply investigated the roles of noncoding RNAs in promoting multiple myeloma and pioneered innovative strategies for their targeting, with translation to clinical trials.
Eugenio is well-published in the field and received national and international grants from different agencies, including the Leukemia & Lymphoma Society, the American Society of Hematology, the International Myeloma Foundation, and the European Hematology Association. In 2019 and 2021, he received the Young Investigator Award from the International Myeloma Society for his contribution to translational research in myeloma.
My long-term scientific interest is to decode the tumor-promoting roles of non-protein coding RNAs (ncRNAs) and to unlock their therapeutic potential to cure multiple myeloma (MM).
Whereas most research into therapeutics focuses on targeting mutations and proteins, we and others have found strong translational potential for ncRNAs, an understudied class of molecules that have important biological functions.
To uncover the role of ncRNAs in MM, I initially focused on microRNAs, a class of small ncRNAs that regulate the production of proteins. I demonstrated that microRNAs miR-21 and miR-125b contribute to MM pathogenesis, and I helped develop an antisense inhibitor of microRNA miR-221 which was well tolerated and therapeutically active in a phase-1 clinical trial in cancer patients. I also pioneered a novel strategy to concomitantly target multiple microRNAs that are produced from a common RNA fragment.
More recently, I have been focusing my research on long (l)ncRNAs. LncRNAs are remarkably abundant in the human genome and affect cellular function by interacting with proteins and nucleic acids. I utilized innovative lncRNA-targeting CRISPR screenings at the genome scale and found a broad tumor-growth dependency on lncRNAs in MM and demonstrated the therapeutic value of lnc-17-92, with inhibitors for translation.
I am an MD, hematologist-oncologist fully committed to basic and translational cancer research. I currently work as Lead Scientist at Dana-Farber Cancer Institute and am a Research Associate at Harvard Medical School. I lead a team of six brilliant scientists within the Riney Family Research Laboratories for Multiple Myeloma (co-directors: Ken Anderson and Nikhil Munshi). My long-term research interest is to decode the key oncogenic features of noncoding RNAs to unlock their therapeutic potential in myeloma and other blood cancers. The goal of my career is to set up my independent lab in a major biomedical institute.