JITC Digest May 2023

By JITC Publications posted 05-17-2023 00:00

Recommend

INSIDE THIS ISSUE:

Letter from the Editor JITC Editor Picks Other Recent JITC ARTICLES JITC Social Media Editors

Letter from the Editor

Dear JITC Readers,

Welcome to the latest edition of the JITC Digest. As the busy meeting season continues, I know many of us are excited to check out the latest research that will be unveiled at next month’s American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago. For those of you attending in person, please stop by the SITC Booth (#2026) in the exhibition hall, where I will be holding a Meet the Editor activity on Sunday, June 4^th, 11–11:30 am CT. It’s a great opportunity to talk about your work and explore opportunities within JITC.

Whether or not you’re attending the meeting, you can follow along with JITC’s social media coverage of ASCO 2023 on Twitter and LinkedIn. Our journal’s social media presence continues to expand, thanks in no small part to our dedicated Social Media Editors Drs. Kristin Anderson, Praveen Bommareddy, and Cheng Sun. Learn more about each of them in the special feature below.

You can also check out this month’s Editor’s Picks, which highlight efforts from around the world and across the research spectrum, including the generation and preclinical characterization of a novel SIRPα blocking antibody, BYON4228, by van Helden et al, and how radiation treatment shapes the immune compartment and interactions with cancer cells within renal cell carcinoma patient tumors from Chow et al.

Regards,

James L. Gulley, MD, PhD, FACP

Journal for ImmunoTherapy of Cancer Interim Editor-in-Chief

JITC Editor Picks

ENGINEERING SECOND-GENERATION TCR-T CELLS BY SITE-SPECIFIC INTEGRATION OF TRAF-BINDING MOTIFS INTO THE CD247 LOCUS

Sangjoon Lah, Segi Kim, In Kang, Hyojin Kim, Cedric Hupperetz, Hyuncheol Jung, Hyeong Ryeol Choi, Young-Ho Lee, Hyeon-Ki Jang, Sangsu Bae, Chan Hyuk Kim
Journal for ImmunoTherapy of Cancer 2023;11:e005519 (5 April 2023)

Research

Summary:

T-cell receptor-engineered T-cell (TCR-T) therapies have the ability to produce tumor antigen-specific T cell responses. In order to improve persistence in vivo, however, co-stimulatory domain signaling is needed to sustain TCR-T cell stimulation and proliferation. Mirroring the development and success of second-generation CAR T cell therapies, the authors of this study engineered a TCR construct to contain a CD3ζ variant containing a truncated 4-1BB signaling domain and tumor necrosis factor receptor-associated factor-binding motif, which increased TCR-T cell expansion and anti-tumor activity in a mouse model.

BYON4228 IS A PAN-ALLELIC ANTAGONISTIC SIRPΑ ANTIBODY THAT POTENTIATES DESTRUCTION OF ANTIBODY-OPSONIZED TUMOR CELLS AND LACKS BINDING TO SIRPΓ ON T CELLS

Mary J van Helden, Seline A Zwarthoff, Roel J Arends, Inge M J Reinieren-Beeren, Marc C B C Paradé, Lilian Driessen-Engels, Karin de Laat-Arts, Désirée Damming, Ellen W H Santegoeds-Lenssen, Daphne W J van Kuppeveld, Imke Lodewijks, Hugo Olsman, Hanke L Matlung, Katka Franke, Ellen Mattaar-Hepp, Marloes E M Stokman, Benny de Wit, Dirk H R F Glaudemans, Daniëlle E J W van Wijk, Lonnie Joosten-Stoffels, Jan Schouten, Paul J Boersema, Monique van der Vleuten, Jorien W H Sanderink, Wendela A Kappers, Diels van den Dobbelsteen, Marco Timmers, Ruud Ubink, Gerard J A Rouwendal, Gijs Verheijden, Miranda M C van der Lee, Wim H A Dokter, Timo K van den Berg

Journal for ImmunoTherapy of Cancer 2023;11:e006567 (17 April 2023)

Research

Summary:

Blockade of the SIRPα-CD47 myeloid checkpoint axis can increase macrophage- and neutrophil-mediated anti-tumor immune responses, which has shown promising results in pre-clinical and early-phase studies. The authors of this study characterized a novel SIRPα-targeting antibody, BYON4228, which demonstrated improved binding efficacy and specificity over previously developed anti-SIRPα agents. When combined with tumor-targeting antibody therapies capable of opsonizing tumor cells, BYON4228 increased myeloid cell-mediated cytotoxicity and phagocytosis in a mouse model and demonstrated tolerable safety in a non-human primate model, progressing this agent to clinical testing expected to begin this year.

TUMOR AND IMMUNE REMODELING FOLLOWING RADIOTHERAPY IN HUMAN RENAL CELL CARCINOMA

Jacky Chow, Adil Khan, Madeline Gaudieri, Brianna J Wasik, Alexis Conway, Kah Teong Soh, Elizabeth A Repasky, Thomas Schwaab, Paul K Wallace, Scott I Abrams, Anurag K Singh, Jason B Muhitch

Journal for ImmunoTherapy of Cancer 2023;11:e006392 (20 April 2023)
Research

Summary:

Using spectral flow cytometry and single-cell RNA sequencing, the authors discovered increased early-activated and effector PD-1⁺CD8 T-cell subsets and transition from stem-like T-cell populations to effector T cells within irradiated renal cell carcinoma patient tumors. Furthermore, radiation enhanced interactions between tumor cells and these effector T-cell subsets through IFN- and TRAIL-mediated interactions, and enrichment for these pathways was associated with survival in patients treated with immunotherapy. These findings demonstrate the contribution of tumor and immune cell radiation-induced immunogenicity and help to elucidate the mechanism for therapeutic synergy between radiation and immune checkpoint blockade.

GEOSPATIAL CHARACTERIZATION OF IMMUNE CELL DISTRIBUTIONS AND DYNAMICS ACROSS THE MICROENVIRONMENT IN CLEAR CELL RENAL CELL CARCINOMA

Nicholas H Chakiryan, Youngchul Kim, Anders Berglund, Andrew Chang, Gregory J Kimmel, Ali Hajiran, Jonathan Nguyen, Carlos Moran-Segura, Daryoush Saeed-Vafa, Esther N Katende, Neale Lopez-Blanco, Jad Chahoud, Phillip Rappold, Philippe E Spiess, Michelle Fournier, Daniel Jeong, Liang Wang, Jamie K Teer, Jasreman Dhillon, Fengshen Kuo, Abraham Ari Hakimi, Philipp M Altrock, James J Mulé, Brandon J Manley

Journal for ImmunoTherapy of Cancer 2023;11:e006195 (25 April 2023)

Research

Summary:

The authors performed geospatial analysis of lymphoid and myeloid cells in human multiplex immunofluorescence clear cell renal cell carcinoma (ccRCC) tumor samples to elucidate the mechanism by which tumor-associated macrophages (TAMs) induce CD8⁺ T-cells into a terminally exhausted state and worsen clinical outcomes. They discovered a worse clinical stage, worse overall- and cancer-specific survival, and a higher proportion of TIM3⁺CD8⁺T cells (suggestive of terminal exhaustion) associated with clustering of CD163⁺M2 like TAMs into the stromal compartment at the tumor–stroma interface. This geospatial metric helps to explain worse clinical outcomes observed despite a paradoxical increase in CD8⁺T-cell infiltration, and an RNA-seq differential gene expression score based on these findings was validated in multiple independent cohorts of patients with ccRCC.

**Other Recent JITC Articles**

VIEW OTHER ARTICLES FROM THIS ISSUE

JITC Social Media Editors

JITC’s Social Media Editors serve a vital role by engaging the social media community, helping expand our global reach, and increasing awareness of the journal and its content across JITC’s social media platforms. Learn more about these dedicated researchers and Social Media Editors.

Dr. Kristin Anderson

Kristin Anderson, PhD, helps manage JITC’s Twitter account and is Assistant Professor at the University of Virginia. Her lab focuses on developing cutting edge strategies for treating solid tumors with engineered adoptive T cell therapy. Dr. Anderson also loves traveling, hiking, and spending time with her family.

Dr. Praveen Bommareddy

Praveen Bommareddy, MS, PhD, helps oversee the JITC LinkedIn profile and is Senior Director of Translational Research at Replimune where his work focuses on oncolytic viruses and intratumoral therapies as immune-modulatory agents and platforms for combination immunotherapy approaches. Outside of his research, Dr. Bommareddy enjoys working out and spending time with his friends.

Dr. Cheng Sun

Cheng Sun, MD, PhD, spearheads JITC‘s WeChat account and is Associate Professor at the University of Science and Technology of China, Hefei. Dr. Sun’s interests include hepatic natural killer (NK) cells, immunotherapy based on NK cells, and temporal and spatial heterogeneity of liver immune cells. Dr. Sun also serves as point of contact for support of other JITC promotional and educational opportunities in China.

Stay up to date on all that is happening with the journal, including deeper dives into recently published articles, early career author spotlights, additional conference coverage of select meetings, and much more by following the journal on LinkedIn, Twitter, and WeChat.

Blogs