JITC Digest October 2023

By JITC Publications posted 10-18-2023 00:00

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Inside this Issue:

Letter from the Editor JITC Editor Picks Meet-the-Editor Sessions JITC at SITC 2023
2023 JITC Awards Popular Archive Articles

Letter from the Editor

Hello JITC Readers,

As I welcome you to the latest edition of the JITC Digest, I am excitedly looking ahead to the 2023 Society for Immunotherapy of Cancer (SITC) Annual Meeting & Pre-Conference Programs, just two weeks away, November 1^st–5^th, at the Convention Center in beautiful San Diego.

There will be a number of exciting JITC events throughout the conference. For those of you attending in person, I encourage you to meet JITC’s Interim Deputy Editor-in-Chief Dr. Sjoerd H. van der Burg while he hosts a Meet-the-Editor session at the SITC booth on Saturday, November 4^th at 12:15 p.m. PDT. Additionally, join me at the awards ceremony later that day at 6:30 p.m. PDT to congratulate the 2023 JITC Best Paper Award winners as well as our first class of graduates from the JITC Peer Review Mentorship Program. If you can’t make it to San Diego, be sure to follow JITC’s coverage on our LinkedIn and X social media accounts. See the special feature below for full details of all the JITC-related events at SITC 2023.

While there will be plenty of outstanding science at the upcoming SITC meeting, there is compelling research published each month in JITC. This month’s highlights include a study by Karen Kai-Lin Fang et al on how anti-CD4-chimeric antigen receptor (CAR4) double-negative T cells (DNTs) can effectively target T-cell acute lymphoblastic leukemia and peripheral T-cell lymphoma. These findings support the potential use of allogeneic CAR4-DNTs as a novel treatment strategy for T-cell malignancies. Wenwen Zhang et al present a single-arm, phase II study that demonstrates the promising efficacy and safety of lenvatinib plus anti-PD-1 antibodies as conversion therapy in unresectable hepatocellular carcinoma. Check out these and other intriguing science stories below.

I hope to see you all in San Diego!

Regards,

James L. Gulley, MD, PhD, FACP

Journal for ImmunoTherapy of Cancer Interim Editor-in-Chief

JITC Editor Picks

ATM inhibition augments type I interferon response and antitumor T-cell immunity when combined with radiation therapy in murine tumor models

Won Jong Jin, Luke M Zangl, Meredith Hyun, Elian Massoud, Kaleb Schroeder, Roxana A Alexandridis, Zachary S Morris
Journal for ImmunoTherapy of Cancer 2023;11:e007474 (19 September 2023)

RESEARCH

Summary:

Some tumors are poorly immunogenic and/or poorly responsive to radiotherapy. Radiation therapy (RT) elicits DNA double-stranded breaks, resulting in tumor cytotoxicity and a type I interferon (IFN) response. Ataxia-telangiectasia mutated (ATM) is a kinase involved in the DNA-damage response and restricts related type I IFN induction. Using two tumor mouse models, MOC2 (head and neck squamous cell carcinoma) and B78 (melanoma), the investigators determined that oral administration of an ATM inhibitor (AZD0156) enhanced RT effects by inducing the type I IFN response and increasing CD8⁺T cell migration and infiltration of tumors. The addition of anti-PD-L1 treatment was required to prevent immune cell exhaustion in this setting. These data demonstrate a potential therapeutic strategy for targeting tumors that are difficult to treat due to their poor immunogenicity and responsiveness to radiotherapy.

Efficacy, safety, and biomarker analysis of nivolumab in combination with abemaciclib plus endocrine therapy in patients with HR-positive HER2-negative metastatic breast cancer: a phase II study (WJOG11418B NEWFLAME trial)

Jun Masuda, Hitomi Sakai, Junji Tsurutani, Yuko Tanabe, Norikazu Masuda, Tsutomu Iwasa, Masato Takahashi, Manabu Futamura, Koji Matsumoto, Kenjiro Aogi, Hiroji Iwata, Mari Hosonaga, Toru Mukohara, Kiyoshi Yoshimura, Chiyo K Imamura, Sakiko Miura, Toshiko Yamochi, Hidetaka Kawabata, Hiroyuki Yasojima, Nobumoto Tomioka, Kenichi Yoshimura, Toshimi Takano
Journal for ImmunoTherapy of Cancer 2023;11:e007126 (13 September 2023)

RESEARCH

Summary:

The purpose of this phase II study was to evaluate the efficacy and safety of the combination of anti-PD1 antibody nivolumab with the CDK4/6 inhibitor abemaciclib and hormone therapy of either fulvestrant (FUL) or letrozole (LET) as first or second-line treatments for hormone receptor-positive HER2-negative metastatic breast cancer. This was a non-randomized, multicohort study with primary endpoint analysis of objective response rate (ORR), and secondary endpoint analyses of toxicity, progression-free survival, and overall survival. The ORRs were 54.5% (FUL cohort) and 40.0% (LET cohort). However, the study was terminated early due to safety concerns, as treatment-emergent (TE) adverse events (AEs) of ≥3 occurred in 92% (FUL cohort) and 100% (LET cohort) of the patients. Thus, while the combination of nivolumab and abemaciclib was active, it caused severe and prolonged immune-related AEs.

Lenvatinib plus anti-PD-1 antibodies as conversion therapy for patients with unresectable intermediate-advanced hepatocellular carcinoma: a single-arm, phase II trial

Wenwen Zhang, Shuang Tong, Bingyang Hu, Tao Wan, Haowen Tang, Feilong Zhao, Tianyu Jiao, Junfeng Li, Ze Zhang, Jinping Cai, Huiyi Ye, Zhanbo Wang, Shiqing Chen, Yafei Wang, Xuerui Li, Fangzhou Wang, Junning Cao, Lantian Tian, Xiaochen Zhao, Mingyi Chen, Hongguang Wang, Shouwang Cai, Minggen Hu, Yuezong Bai, Shichun Lu
Journal for ImmunoTherapy of Cancer 2023;11:e007366 (20 September 2023)

RESEARCH

Summary:

Combination therapy of tyrosine kinase inhibitors such as lenvatinib and anti-programmed cell death protein-1 (PD-1) antibodies has achieved a high tumor response rate in both the first- and second-line treatment of advanced hepatocellular carcinoma (HCC). In this single-arm, phase II study, the investigators examined whether the same combination therapy could be applied to patients with unresectable intermediate-advanced HCC to convert their disease into resectable HCC. Primary endpoint analysis showed a conversion success rate of 55.4%. Analysis of the tumor microenvironment prior to treatment showed significant enrichment of CD8⁺T cells in responders versus non-responders. This trial shows promising efficacy and tolerability for combination lenvatinib plus anti-PD-1 antibodies as conversion therapy in unresectable HCC and identifies pre-existing CD8⁺T cells as a promising biomarker for response to this regimen.

Targeting T-cell malignancies using allogeneic double-negative CD4-CAR-T cells

Karen Kai-Lin Fang, Jongbok Lee, Ismat Khatri, Yoosu Na, Li Zhang
Journal for ImmunoTherapy of Cancer 2023;11:e007277 (7 September 2023)

RESEARCH

Summary:

Treatment options for patients with relapse/refractory T-cell malignancies are limited and chimeric antigen receptor (CAR)-T cell therapy is challenging due to the possible blast contamination and fratricide of CAR-T cells targeting T-lineage antigens. To address this challenge, the investigators explored the antitumor activity of allogeneic double negative T cells (DNTs) and anti-CD4-CAR (CAR4)-DNTs in T-cell malignancies. DNTs and CAR4-DNTs were tested for antitumor immunity both in vitro and in vivo via xenograft models of T-cell acute lymphoblastic leukemia (T-ALL) and peripheral T-cell lymphoma (PTCL). Results showed some antitumor effects in DNTs, with significantly enhanced potency in CAR4-DNTs both in vitro and in vivo. These results demonstrate that CAR4-DNTs can effectively target T-ALL and PTCL, and support allogeneic CAR4-DNTs as an adoptive cell therapy for T-cell malignancies.

**Other Recent JITC Articles**

view other articles from this issue

JITC Meet-the-Editor Sessions

Upcoming opportunities await on both sides of the Atlantic Ocean to meet JITC‘s Interim Deputy-Editor-in-Chief Sjoerd H. van der Burg, PhD. If you are attending the European Society for Medical Oncology (ESMO) Congress in Madrid, or the SITC Annual Meeting & Pre-Conference Programs in San Diego, stop by to say hello, discuss your research, and share your thoughts on JITC and the field during these two JITC Meet-the-Editor sessions. See below for full details.

ESMO 2023
Saturday, October 21^st, 2023
11 a.m.–12 p.m. CET
IFEMA Madrid - BMJ Booth (P723 in Publishers exhibit area)
Madrid, Spain

SITC 2023
Saturday, November 4^th, 2023
12:15 p.m.–1:15 p.m. PDT
San Diego Convention Center - SITC Booth
San Diego, California (United States)

JITC at SITC 2023

Attending SITC 2023? Discover a number of ways to interact with JITC during the society’s 38^th Annual Meeting and Pre-Conference Programs, November 1^st–5^th.

Friday, November 3^rd

Congratulate Jeffrey S. Weber, MD, PhD as recipient of this year’s Pedro J. Romero Service to JITC Award (7:50–8:20 a.m. PDT – Hall C – Session 101)

Saturday, November 4^th

Celebrate this year’s JITC Best Paper Award recipients along with the journal’s Peer Review Mentorship Program class of 2023 during the Awards Ceremony (6:30–7:00 p.m. PDT – Hall C – Session 209)

Throughout the Meeting

Additional JITC content will be available throughout the Annual Meeting and Pre-Conference Programs.

View and share SITC 2023 abstracts published in JITC as of Tuesday, October 31^st
Follow @jitcancer on X and LinkedIn for additional coverage of SITC 2023
Visit the SITC exhibit booth to learn more about the journal

**2023 JITC Awards**

2023 Pedro J. Romero Service to JITC Award
Congratulations to Jeffrey S. Weber, MD, PhD, the recipient of this year’s Pedro J. Romero Service to JITC Award. Nominated and selected by Society for Immunotherapy of Cancer (SITC) colleagues in recognition of his commendable dedication to the journal and distinguished record of service, Dr. Weber has made innumerable contributions to JITC and the immuno-oncology field.

Jeffrey S. Weber, MD, PhD
Laura and Isaac Perlmutter Cancer Center at NYU Langone Health (USA)

2023 JITC Best Paper Award Recipients
The JITC Best Paper Awards celebrate excellence in scientific research and are awarded to researchers demonstrating leadership in the field as well as innovation and high-quality execution and discussion in their manuscripts and are nominated by JITC’s Editorial Board. Congratulations to the 2023 JITC Best Paper Award recipients.

Basic Tumor Immunology
Laura Fernandez-Rodriguez, PhD – University of Basel and University Hospital of Basel (Switzerland)
Chiara Cianciaruso, PhD – AGORA Cancer Research Center (Switzerland)
Dual TLR9 and PD-L1 targeting unleashes dendritic cells to induce durable antitumor immunity

Clinical/Translational Cancer Immunotherapy
Benny Johnson, DO – The University of Texas MD Anderson Cancer Center (USA)
Phase II study of durvalumab (anti-PD-L1) and trametinib (MEKi) in microsatellite stable (MSS)
metastatic colorectal cancer (mCRC)

Immune Cell Therapies and Immune Cell Engineering
Katherine P. Mueller, PhD – University of Wisconsin-Madison (USA)
Nicole J. Piscopo, PhD – University of Wisconsin-Madison (USA)
Production and characterization of virus-free, CRISPR-CAR T cells capable of inducing solid tumor regression

Immunotherapy Biomarkers
Myrto K. Moutafi, MD – Yale University School of Medicine (USA)
Magdalena Molero-Abraham, PhD – Instituto de Investigación Hospital 12 de Octubre (Spain)
Spatially resolved proteomic profiling identifies tumor cell CD44 as a biomarker associated with sensitivity to PD-1 axis blockade in advanced non-small-cell lung cancer

Oncolytic and Local Immunotherapy
Julia Katharina Schwarze, MD, MSc – Universitair Ziekenhuis (UZ Brussel) (Belgium)
Intratumoral administration of CD1c (BDCA-1)+ and CD141 (BDCA-3)+ myeloid dendritic cells in combination with talimogene laherparepvec in immune checkpoint blockade refractory advanced melanoma patients:
a phase I clinical trial

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