Recently, the clinical research on the treatment of advanced biliary tract tumors using ScTIL technology, a Chinese-original peripheral blood TIL-like cell therapy, was published in "Cell Reports Medicine," a subsidiary journal of "CELL." Although this is only a proof-of-concept clinical study, it has shown promise in solid tumors.ImmunityIn the field of treatment, it represents a major conceptual breakthrough—humanity's first successful isolation of TIL-like cells from peripheral blood and their genetic modification, with clinical efficacy verified in cholangiocarcinoma, the cancer with the highest malignancy. Research data shows that, compared to the control group, ScTIL demonstrated efficacy in advanced biliary tract cancers that were previously treatment-resistant.Cancer PatientsThe overall survival (OS) was extended by 5 times, and its OS was even significantly better than the first-line standard treatment. The PI of this study isPeking Union Medical College HospitalProfessor Haitao Zhao from the Hepatobiliary Surgery Department; ScTIL cell preparation and technical support were provided by Chineo (Beijing) Medical Technology Co., Ltd.

In recent years, PD-1 monoclonal antibody has become mainstream.Anticancer DrugThing, cell therapy technology such asCAR-TAnd tumor-infiltrating lymphocytes (TIL) have successively received approvals for new drugs to be marketed. However, conquering cancer (especially solid tumors) remains a formidable challenge. The article points out that the following "three major difficulties" need to be overcome to achieve this:

1) Heterogeneity, i.e., how to enable T cells to recognize all kinds of different antigens.Cancer CellsCAR-T and other targeted therapies can only recognize one or two targets while missing others, which is an important reason for the limited efficacy of such technologies.

2) The microenvironment, namely how to enable T cells to prevail when they come into direct contact with cancer cells. Cancer cells can suppress T cells, causing them to lose their functionality.

3) T cell expansion, namely, how to expand the "total force" of T cells in a way that is "fast, good, and economical".

PD1 antibody can only counteract the microenvironment, without considering the other two challenges. TIL therapy aims to overcome heterogeneity but relies on surgical sampling, chemotherapy-induced lymphodepletion preconditioning, high-dose IL2, and massive in vitro expansion. Hence, it has numerous limitations and drawbacks, including restricted application scenarios, high preparation failure rates, severe toxic side effects, high costs, and long preparation cycles.

ScTIL aims to simultaneously address three major challenges by integrating the following three innovative points:

First, bypass surgical sampling and only require peripheral blood apheresis to select cTILs (classical TIL-like cells) — natural T cells similar to TIL in specifically recognizing heterogeneous tumors, to overcome heterogeneity;

Second, with a "receptor enhancement" gene modification, the inhibitory signals that cancer cells exert on T cells are reversed into activation signals (brakes turned into accelerators) to overcome the microenvironment challenge.

Third, the gene modification with CAR targeting CD19 utilizes the stimulation of B cells in the patient's body to achieve the expansion of ScTIL in vivo, without the need for excessive expansion in vitro.

The integration of these three innovations can also spare patients from chemotherapy and IL2, while simplifying the cell production process—shortening the cycle and reducing costs.

This "three-in-one" strategy completely breaks away from the constraints of CAR-T and TIL in terms of technical routes, overturning the underlying technology.

This is not the first clinical study of the "three-in-one" strategy. The first clinical study of ScTIL for treating pan-cancer solid tumors was published in *Cancer Immunology Research* in 2024, reporting cases of complete response (CR), a high disease control rate, and good safety.

Chineo's earlier-generation "three-in-one" strategy — enhanced receptor, CD19-CAR-modified TIL cell (STIL, or "Super TIL") therapy for solid tumors — was published slightly earlier in *Biomedicine & Pharmacotherapy*, reporting partial response (PR) cases, a high disease control rate, and good safety.

This ScTIL study treated a total of 10 patients with advanced bile duct tumors who were ineffective after treatment or relapsed after surgery.

Preparation cycle significantly shortened:

The median time from peripheral blood collection to cell infusion (vein-to-vein) was 18 days – including a 7-day quality control cycle and the factor of patients being unable to receive timely reinfusion due to the pandemic at that time, which is significantly shorter than TIL therapy. (It has been reported that the latest generation ScTIL technology from Chineo has reduced the "vein-to-vein" cycle to 2 days.)

Safety: Exceeds expectations.

None of the subjects observed cytokine release syndrome (CRS) or autoimmune toxicity. The added advantage is that ScTIL does not require lymphodepleting chemotherapy or IL-2, significantly enhancing safety and patient tolerance.Quality of Life。

Efficacy: Significant improvement in OS

Given that ScTIL, by design, utilizes CD19-CAR to stimulate and expand B cells, post-hoc analysis introduced grouping based on baseline B cell levels. Patients with baseline B cell levels far below normal are mechanistically unlikely to benefit and can be considered the control group, whereas others form the treatment group.

Data show that, compared with the control group, the disease control rate (DCR) in the treatment group was 100% versus 0%, a dramatic difference; the median overall survival (mOS) was 18.3 months versus 3.2 months, differing by more than five times. OS is the ultimate indicator for evaluating tumor efficacy.FDAwith particular emphasis on this indicator).

Compared to standard treatments, ScTIL demonstrates greater potential. The median overall survival (mOS) for the first-line standard treatment GC regimen (gemcitabine + cisplatin) in biliary tract cancer is 11.7 months, while the "GC + K drug" triple combination regimen extends it to 12.7 months. The K drug (a PD-1 monoclonal antibody and a long-time global best-selling "blockbuster drug") only adds one extra month of overall survival (OS) for first-line patients when combined with chemotherapy. In contrast, ScTIL monotherapy achieves an mOS of 18.3 months in later-line patients, not only surpassing the performance of the K drug but even extending survival by 50% compared to the first-line triple combination regimen.

As a cell therapy, ScTIL brings a paradigm revolution compared to traditional TIL and solid tumor CAR-T: First, ScTIL only requires apheresis without surgery, which not only significantly expands application scenarios but also greatly improves preparation success rates; Second, it has better safety as ScTIL eliminates the need for chemotherapy-induced lymphodepletion and IL2, with no severe CRS or On-Target-Off-Tumor toxicity; Third, ScTIL does not require excessive in vitro expansion, significantly reducing preparation time and cost; Fourth, ScTIL can basically be infused on an outpatient basis, significantly decreasing the occupation of medical resources (beds, medical staff).

This study confirms the scientific and feasibility of the ScTIL technology route. Although larger sample-sized confirmatory studies are still needed, it must be said that as an original底层platform innovation technology in China, ScTIL has brought a breakthrough in the paradigm of solid tumor cell therapy and shown great potential for future clinical applications.