In-Vivo Cell Therapy Model Aims to Reduce Manufacturing Challenges

Under a newly formed strategic partnership, Cue Biopharma and ImmunoScape aim to address longstanding challenges in solid tumor treatment, particularly the limited persistence, tolerability, and scalability of engineered T-cell therapies. The collaboration, announced on Nov. 6, 2025, combines complementary scientific approaches intended to enable targeted immune activity directly within the patient’s body, rather than relying solely on complex external cell manipulation (1).

Under the agreement, the companies will advance a novel in-vivo cell therapy strategy called Seed-and-Boost. This approach uses tumor-specific T-cell receptor–engineered T cells (TCR-Ts) from ImmunoScape as the initial therapeutic component. Following infusion of these cells, Cue Biopharma’s CUE-100 series of targeted biologics will be administered to promote their in-vivo expansion.

“ImmunoScape is excited to partner with Cue Biopharma to pioneer this novel immunotherapy against solid tumors and potentially provide patients with a promising treatment option,” said Michael Fehlings, CEO, ImmunoScape, in a company press release (1).

How could in-vivo T-cell expansion improve solid tumor therapy?

The collaboration focuses on activating and expanding infused TCR-Ts after they enter the patient (the Boost), instead of manufacturing large quantities of cells externally. This strategy is designed to reduce manufacturing complexity and potentially support deeper and more durable therapeutic responses in solid tumors, where current engineered cell therapies have shown constrained efficacy (1).

The approach aims to limit broad immune system activation while enhancing the population of tumor-specific T cells capable of infiltrating cancerous tissue. Data from preclinical studies across multiple cancers, including pancreatic and ovarian tumors, support its potential (2). The companies expect to advance investigational new drug-enabling studies for submission in 2027.

The CUE-100 series comprises injectable biologics that deliver precise signaling to activate specific disease-targeted T cells. The molecules are based on a framework that engages the TCR and delivers interleukin-2 (IL2) in a controlled manner. Early clinical studies have shown activity across metastatic cancers without the severe toxicities typically associated with immune-modulating IL2 (3).

What makes tumor-specific TCRs a key component in this therapeutic approach?

ImmunoScape brings a library of highly potent TCRs to the partnership. These TCRs target shared antigens across common human leukocyte antigen profiles worldwide. When used with the CUE-100 series, these TCRs may enable cell therapies to combat a broader spectrum of solid tumors while aiming to avoid the systemic immune effects that limit many current technologies (1).

“Based on our extensive preclinical work, we believe this Seed-and-Boost approach will transform T-cell therapy for long-term efficacy against a range of solid tumors while avoiding the deleterious side effects of broad immune activation,” said Fehlings in the release. “We aim to transform patients’ lives by enabling superior cell therapy and streamlining the patient journey.”

Why does this collaboration matter for future clinical development?

The agreement signals continued momentum in transitioning immunotherapies from cell manufacturing–heavy approaches toward more scalable methods. If successful, the platform could support wider accessibility and reduced patient and industry burden (1).

“We believe this strategic collaboration with ImmunoScape represents a significant development for treating solid tumors with immunotherapy,” said Usman Azam, president and CEO, Cue Biopharma, in the release. “It positions the company to focus on our autoimmune disease programs and continue to advance the Immuno-STAT platform for oncology with our partners at ImmunoScape.”

The agreement includes an upfront payment totaling $15 million along with a future royalty structure and the acquisition by Cue Biopharma of a 40% equity stake in ImmunoScape. The partners plan to jointly advance the therapy through early development, with the goal of expanding treatment possibilities for patients facing difficult-to-treat cancers.

References

1. Cue Biopharma. Cue Biopharma and ImmunoScape Announce Strategic Collaboration to Develop Breakthrough Cell Therapy Approach for Solid Tumors. Press Release. Nov. 6, 2025.
2. Anderson, K. G.; Voillet, V.; Bates, B. M.; et al. Engineered Adoptive T-cell Therapy Prolongs Survival in a Preclinical Model of Advanced-Stage Ovarian Cancer. Cancer Immunol. Res. 2019, 7 (9), 1412–1425. DOI: 10.1158/2326-6066.CIR-19-0258
3. Quayle S. N.; Girgis, N.; Thapa, D. R.; et al. CUE-101, a Novel E7-pHLA-IL2-Fc Fusion Protein, Enhances Tumor Antigen-Specific T-Cell Activation for the Treatment of HPV16-Driven Malignancies. Clin Cancer Res. 2020, 26 (8), 1953–1964. DOI: 10.1158/1078-0432.CCR-19-3354