On November 11, 2026 Immunofoco, in collaboration with Renji Hospital, Shanghai Jiao Tong University School of Medicine, and Shanghai East Hospital, Tongji University, reported a novel in vivo T-cell engager (TCE) delivery strategy using CD19-targeted lentiviral vectors at the 41st Annual Meeting of the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) (SITC 2026), held November 4–8 in Phoenix, Arizona. The approach explores the engineering of tumor cells and B cells into cellular factories capable of continuously secreting CD3×CD19 bispecific T-cell engagers (BiTEs), with the aim of enabling sustained T-cell activation and tumor elimination.

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The study was presented as a poster entitled "Engineering lymphoma cells as in situ CD3×CD19 BiTE factories via CD19-targeted lentiviral delivery enables sustained T-cell engagement and tumor elimination."

Abstract

Background

CD3×CD19 T-cell engagers (TCEs) have demonstrated significant clinical benefit in B-cell malignancies and have been successfully translated into approved therapies[1,2]. However, their clinical application remains limited by short serum half-life, the need for continuous or repeated administration, and treatment-related toxicities associated with systemic exposure[2-4]. To address these challenges, we developed a lymphoma-targeted in vivo gene delivery strategy that selectively reprograms lymphoma cells into endogenous CD3×CD19 BiTE-producing factories, enabling sustained local BiTE secretion, continuous T-cell engagement, and bystander elimination of neighboring non-transduced tumor cells.

Methods

We developed an engineered lentiviral delivery platform that contains a CD19-targeting envelope, selectively transduct CD19+ lymphoma cells to drive sustained endogenous CD3×CD19 BiTE secretion. In vitro, transduction efficiency, BiTE secretion, T-cell activation, and cytotoxicity were evaluated in Raji and Nalm6 models. In vivo efficacy was assessed in Nalm6-Luc-bearing NSG mice receiving human PBMCs, with longitudinal monitoring of tumor burden, serum BiTE levels, tumor transduction, and survival.

Results

The CD19-targeted lentiviral platform selectively transduced CD19-positive lymphoma cells, with transduction efficiencies of approximately 9–18% in Raji cells and 15–29% in Nalm6 cells 2 days after infection.

Transduced tumor cells continuously secreted functional CD3×CD19 BiTE, reaching peak concentrations of approximately 300 pg/mL in both Raji and Nalm6 cultures. Tumor-derived CD3×CD19 BiTE induced potent T-cell responses, with 50–80% proliferating T cells, 15–30% PD-1+Lag3+ T cells, over 70% lymphoma cell killing, and IFN-γ secretion exceeding 900 pg/mL. CD20-targeted BiTE showed limited activity in CD20-negative Nalm6 cells, which showed target-dependent activity.

In Nalm6-bearing NSG mice, systemic administration of the CD19-targeted BiTE virus following human PBMC infusion resulted in durable tumor clearance with bioluminescence signals remaining near baseline throughout the observation period (>58 days). In contrast, mice treated with blinatumomab (recombinant CD3×CD19 BiTE protein) plus PBMC exhibited frequent tumor relapse. PBMC alone, BiTE virus alone, and untreated controls showed rapid disease progression.

Conclusions

Tumor-targeted in vivo lentiviral delivery reprograms CD19-positive lymphoma cells into endogenous CD3×CD19 BiTE factories, enabling sustained BiTE production, continuous T-cell activation, and bystander tumor killing. This strategy achieved durable lymphoma elimination and prolonged survival with superior efficacy compared with conventional BiTE administration, supporting a promising in vivo immune engineering approach for B-cell malignancies.

Advancing Dual-Engine Cell Therapy Platforms

Immunofoco continues to advance its dual-engine technology platforms spanning autologous CAR-T and in vivo CAR-T therapies. The company is conducting research into key technologies including cell engineering, targeted in vivo lentiviral delivery, and the in situ expression of immune effector molecules. Going forward, Immunofoco will continue to advance the research and validation of these technologies, explore their potential applications across different disease areas, and build a scientific foundation for future product development and clinical translation.

(Press release, Immunofoco, NOV 11, 2026, View Source [SID1234674618])