Unlocking Gentler, Cost-Efficient TIL Therapy For Cold Tumors

A conversation between CuraCell CEO Torbjörn Ström and Clinical Leader Executive Editor Abby Proch

T-cell therapies can be highly effective, but they’re not without their drawbacks. They can cause adverse health events, create manufacturing complexities, have limited effectiveness in solid tumors, and come at a high cost, thus inhibiting patient access.

CuraCell is working to overcome those challenges with its CytoPLY platform, which harnesses a patient’s own tumor-infiltrating lymphocytes (TILs) to recognize and attack cancer. It hopes to improve TIL functionality, expansion, and anti-tumor activity without genetic modification. By rejuvenating dysfunctional tumor-resident T cells and accelerating their growth outside the body, the platform seeks to create a more potent and diverse therapeutic product with stronger cytokine production, better persistence, and faster manufacturing.

In this interview, Torbjörn Ström, head of clinical operations, discusses how those scientific insights are shaping CC-38, CuraCell’s first-generation clinical candidate, now being tested in an open-label Phase 1/2a study in metastatic colorectal and prostate cancer. He also explains what the company has learned from named-patient experience, how it is approaching dosing and preconditioning, and why making effective T-cell therapy more accessible in cold solid tumors remains the program’s central goal.

Clinical Leader: Based on your experience treating patients with CytoPLY derived TILs, which patient types appear to derive the greatest benefit? How have these real-world observations influenced your approach to patient identification and enrollment?

Torbjörn Ström: Based on our pre-assessor of CC-38 experience through named-patient treatments, the number of patients treated remains limited, and therefore conclusions should be drawn cautiously. However, one encouraging observation has been that CytoPLY-derived TILs demonstrated clinical activity across several distinct cold solid tumor types, including prostate cancer, glioblastoma, pancreatic cancer, and renal cell carcinoma.

This supports our underlying hypothesis that a polyclonal, unselected TIL approach may have broader applicability than many targeted therapies, which are often restricted to patients with specific biomarkers, mutations, or antigen targets. Rather than focusing on a narrowly defined patient population, our strategy is to harness each patient's existing anti-tumor immune repertoire and potentially address a wider range of cold solid tumors with significant unmet medical need.

These early observations have informed our current clinical development strategy and support the broad enrolment approach being evaluated in the ongoing CC-38 Phase 1/2a trial.

What are the current manufacturing lead times, and how do these timelines compare with other cell therapy products?

CC-38 is a personalized autologous cell therapy, and the current manufacturing timeline is broadly in line with other similar autologous cell therapies, with approximately a one-month interval from tumor harvest through manufacturing and product release.

While shorter manufacturing times are always desirable, it is important to recognize that patients enrolled in our current Phase 1/2a trial have typically exhausted available standard-of-care treatment options. By the time patients are recruited into the study, previous therapies have already been ineffective, and treatment decisions are focused on identifying the next potential therapeutic option. During the manufacturing period, patients continue to receive clinical monitoring, supportive care, and, where appropriate, bridging therapies to help manage their disease until their personalized cell product is ready for administration.

One important insight from our named-patient experience was that patients with cold solid tumors may benefit from repeated TIL administrations. This observation contributed to the development of the current CC-38 regimen, which incorporates multiple dosing cycles with the aim of enhancing and sustaining the anti-tumor immune response. As a result, our focus has been not only on manufacturing efficiency but also on designing a treatment protocol that maximizes the therapeutic potential of the patient's T cells.

While CC-38, like other personalized cell therapies, requires time to manufacture from a patient's own tumor tissue, this approach enables the creation of a highly individualized treatment tailored to each patient. Our focus is therefore on combining an efficient manufacturing process with strong clinical outcomes, scalable operations, and a practical treatment pathway that can support broad patient access in the solid tumor setting.

What preconditioning regimen does CC-38 require? To what extent is hospitalization, inpatient monitoring, or other intensive healthcare support anticipated, and how might these factors influence the overall cost of care compared with other cell therapies?

TIL therapy has demonstrated a well-established safety profile. Historically, however, TIL treatments have often been combined with intensive lymphodepletion regimens and high-dose IL-2 administration, both of which can cause treatment-related toxicity and increase the need for prolonged hospitalization and monitoring in some patients.

With CC-38, we have designed the treatment regimen to use a more gentle preconditioning approach that eliminates fluderabine and uses a lower dower dose of cyclophosmaide, aiming to reduce treatment burden while maintaining efficacy. We expect patients will need a five hospital days associated with treatment administration and monitoring, which may decrease if no complications occur. This has important implications not only for patient experience but also for healthcare resource utilization and overall treatment costs.

When viewed in the broader context of cell therapy, the operational burden of CC-38 compares favorably with more complex approaches such as CAR T cell therapies. Combined with a simpler manufacturing process and lower expected cost of goods, our goal is to develop a TIL-based therapy that can be delivered in a more resource-efficient manner while expanding access to patients with cold solid tumors.

What have you learned about site execution, and how might these findings support broader adoption across more treatment centers?

We chose to conduct the current Phase 1/2a trial at the same hospital where the named-patient treatments using the predecessor of CC-38 were performed. This approach allows us to build on the extensive clinical and operational experience already established with the treatment protocol, ensuring continuity in patient management, manufacturing coordination, and safety monitoring as we evaluate CC-38 in a larger patient population.

A single-center approach also provides greater consistency during clinical development, enabling us to generate robust safety and feasibility data while minimizing variability between treatment sites. Because CC-38 utilizes an unselected, polyclonal TIL approach rather than targeting a narrow biomarker-defined patient population, we have not experienced the same patient identification challenges often seen with more targeted cell therapies and therefore have sufficient access to eligible patients for this stage of development.

While the trial is formally conducted through a single primary center, the hospital is currently collaborating with two additional hospitals for patient identification and referral. As the program advances toward later-stage development, multi-center trials will be necessary to achieve the participant number required.

What contribution have named-patient treatments made to the development of the CC-38 program?

The named-patient treatments provided a valuable opportunity to refine and further develop the treatment protocol before entering formal clinical development. While the patient numbers were limited, the experience generated important clinical, operational, and manufacturing insights that directly influenced the design of our current Gen-1 product and trial protocol.

One key learning was the potential benefit of repeated dosing in cold solid tumors, which contributed to the multi-dose regimen now being evaluated in the Phase 1/2a trial. The named-patient experience also allowed us to optimize patient management procedures, manufacturing logistics, and the implementation of a gentler preconditioning regimen compared with traditional TIL protocols.

These learnings continue to shape the development of our next-generation Gen-2 platform, where we are further optimizing manufacturing, treatment protocols, and scalability to support future Phase 2b trials and eventual commercialization.

What have you learned about the patient experience during the trial, and how is that shaping a more patient-centric development and commercialization strategy?

As an autologous ATMP, CC-38 is intended to be administered at hospitals with the appropriate oncology infrastructure, including 24-hour emergency services and multidisciplinary teams experienced in advanced cancer care.

TIL therapy itself has demonstrated a favorable safety profile over many years of clinical use. The primary treatment burden and potential side effects are generally associated with the preconditioning regimen and supportive treatments, rather than the administration of the patient's own T cells.

Our experience has shown that administration is relatively straightforward and not a major driver of healthcare resource utilization or cost. In contrast to many conventional cancer treatments, such as chemotherapy, which often require repeated treatment cycles and ongoing hospital visits over extended periods, CC-38 is designed as a defined treatment course. Following completion of treatment, patients typically require routine clinical follow-up rather than ongoing treatment. As a result, our development strategy has focused on maintaining efficacy while reducing the overall treatment burden through protocol optimization and shorter hospitalization requirements.

This combination of manageable tolerability, streamlined administration, and the use of unmodified cell therapy has the potential to reduce manufacturing complexity and production costs, support broader patient eligibility, and enable a more cost-efficient treatment pathway than many other advanced cell therapy approaches.

About The Expert:

Torbjörn Ström is an experienced clinical project manager and research professional with experience in healthcare, pharmacovigilance, and clinical trials management. Torbjörn has held pivotal roles at AstraZeneca, Ipsen, Labcorp, and PharmaRelations, managing clinical trials, register studies, and investigator-sponsored trials.

He is a qualified nurse from the Red Cross College of Nursing and has specialized training in intensive care and research methodology at Karolinska Institutet as well as business administration from Örebro University. Torbjörn's work is further reflected in multiple publications and presentations that demonstrate his commitment to advancing healthcare and clinical research.