JITC Digest March 2026

By JITC Publications posted 2 hours ago

INSIDE THIS ISSUE:

Letter from the Editor| JITC Editor Picks|Special Series: SITC 40^th Anniversary|Popular Archive Articles

Letter from the Editor

Hello JITC Readers,

We are quite fortunate to have several philanthropic agencies supporting and promoting the development of novel therapies in the IO space. These include the recent fundraiser for the Emily Whitehead Foundation that I was privileged to attend as part of the G-Rex® Grant Tour at The Franklin Institute in Philadelphia last month. The Foundation provides counseling and support to families preparing for cell therapy, while promoting new treatments for pediatric cancers.

The namesake of the Emily Whitehead Foundation was the first pediatric patient to be treated with CAR T-cell therapy. Emily was cured of acute lymphoblastic leukemia at the age of seven, and during this Women's History Month, it is worth celebrating her story. Now more than 13 years after her successful treatment, Emily continues to inspire patients, survivors, and researchers across the globe.

Another philanthropic group providing support for investigators developing cell and gene therapy is the Alliance for Cancer Gene Therapy (ACGT), which is celebrating its 25^th year. I have been privileged to be part of ACGT since its founding and am honored to now serve as Chair of the Scientific Advisory Council. This month, ACGT Summit 2026 will be held in New York, an annual invitation-only gathering that convenes the field’s most influential physician-scientists shaping the future of curative cell and gene therapies for solid tumor cancers. During this year’s event, ACGT will recognize the recipients of the ACGT Investigator Award in Cell and Gene Therapy for Gynecological Cancer Research and the ACGT–Cinelli Family Foundation Investigator Award in Cell and Gene Therapy for Breast Cancer, celebrating outstanding innovators driving the field forward in women’s cancers. ACGT will also announce a Request for Applications for the 2026 ACGT Investigator Award in Cell and Gene Therapy for solid tumor cancers. The RFA will be available on April 1 on the ACGT website.

Immune Cell Therapies and Engineering

We have a section in JITC dedicated to Immune Cell Therapies and Immune Cell Engineering, headed up by Section Editors, Aude Chapuis, MD, at the Fred Hutchinson Cancer Research Center and Marco L. Davila, MD, PhD, Roswell Park Comprehensive Cancer Center. The rapid advances in cell therapies for hematologic malignancies and solid tumors have been captured at SITC’s annual meeting and in the pages of our Journal, as this section has steadily grown over the years. While capital investment in these areas has stalled, the academic advances have been thrilling with convergence of bispecific engagers, immune checkpoint blockade and cellular therapies. Some of these we will share with you for this month’s digest.

Highlighted Manuscripts

This month, I would like to emphasize the importance of cell therapy as part of our mission for the Journal. Here we focus on “what the study adds” messaging from the articles themselves, one of which is a commentary on a prior publication in JITC, “Engineering TME-activated CD47-specific CAR macrophage via Arg1 promoter for safe and effective solid tumor immunotherapy.” I encourage you to peruse them and the other papers published in JITC this last month.

Regards,

Michael T. Lotze, MD
Editor-in-Chief
Journal for ImmunoTherapy of Cancer

JITC Editor Picks

Antigen–IL-2 CAR-enhancer drives CAR-T fate and stemness, enhancing antitumor efficacy across models independent of IL-2Rα

From the Authors – What This Study Adds:

Using protein engineering, we generated several IL-2 muteins with graded affinities for IL-2Rα and IL-2Rβγ and tested them in rigorous in vivo models. We demonstrate that CAR-enhancer (CAR-E) activity is entirely independent of IL-2Rα and strictly dependent on IL-2Rβγ signaling. Importantly, IL-2Rα-sparing CAR-Es remain highly potent across diverse tumor models, including with patient-derived CAR-T cells and in humanized mice, achieving durable expansion, resistance to exhaustion, and memory formation while improving both selectivity and safety.

Donor-derived CD19-targeted CAR-NK cells induce complete remission in a child with relapsed B-ALL after failure of blinatumomab and autologous CD19-targeted CAR-T

From the Authors:

We report a challenging case of a boy with relapsed B-cell acute lymphoblastic leukemia (B-ALL) after blinatumomab who failed to respond to autologous CD19-targeted CAR-T cell therapy and mitoxantrone-based reinduction chemotherapy. The patient achieved a complete remission after donor-derived CD19-targeted CAR-NK cell infusion, experiencing a grade 3 immune effector cell-associated neurotoxicity syndrome (ICANS), which was completely controlled by timely treatment. Then, the patient received the same donor-derived hematopoietic stem cell transplantation (HSCT) and remains in complete remission for a year post-HSCT. Our case provides an example of the utility of CAR-NK cell therapy as a bridge to HSCT in treating pediatric relapsed/refractory B-ALL, despite the occurrence of ICANS as a manageable toxicity.

Engineering macrophages for effective and safe targeting of CD47 cancer cells in the tumor microenvironment

From the Authors:

Du et al developed pArg1-CD47 CAR-Mφ based on intrinsic Arg1 promoter responsiveness for TME-specific activation of cytotoxicity, effectively overcoming SIRPα inhibition against CD47+cancer cells. In preclinical murine models of breast and gastric cancer, this macrophage cell therapy demonstrated significant regression of established tumors with minimal toxicity towards erythrocytes. Although translating this work from mice to humans remains a significant challenge, it provides hope for the design of myeloid cell therapies with antitumoral efficacy and safe profile for solid tumors.

Effective allogeneic natural killer cell therapy for pancreatic adenocarcinoma avails conserved activating receptors and evades HLA I-driven inhibition

From the Authors – What This Study Adds:

We explore how the naturally occurring heterogeneity of activating and inhibitory receptor expression with and between individuals impacts recognition of pancreatic ductal adenocarcinoma (PDAC) tumor cells. We find that the natural cytotoxicity receptors and NKG2D are among the most likely activating receptors to be expressed on NK cells responding to PDAC. However, interactions between inhibitory killer immunoglobulin-like receptors (KIR) and class I human leukocyte antigens (HLA) dominantly inhibit NK cell killing. To enable NK cell reactivity without the liability of inhibition, we demonstrate that NK cells can be selected intentionally from allogeneic HLA-mismatched donors, where they retain programmed functionality but are ignorant to the HLA-driven signals for inhibition present on the tumor cells.

Special Series: SITC 40th Anniversary: I-O Progress and Potential

In celebration of the 40th Anniversary of the Society for Immunotherapy of Cancer (SITC), JITC proudly presented a special series of commentaries from luminaries in the field of immuno-oncology. Numerous SITC Fellows of the Academy of Immuno-Oncology and Richard V. Smalley Memorial Award recipients put pen to paper to provide their insights into current achievements in various areas of the field while also sharing their personal, forward-looking vision of where the field is moving in the upcoming decades.

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