#1 Clinical Trials Search in Europe

TIL CELLS

TIL cells (tumor-infiltrating lymphocytes) are immune cells taken from a person’s tumor, grown and prepared in a lab, and then given back by infusion to help the immune system fight cancer. Several clinical trials are studying TIL-based treatments in different cancers, including advanced solid tumors, metastatic melanoma, and stage III/IV ovarian cancer. These studies mainly look at safety (side effects) and how well the treatment may control or shrink tumors.

Table of Contents

What are TIL cells?

TIL cells stands for tumor-infiltrating lymphocytes. These are immune cells, mainly T-cells, that are already inside a person’s tumor. The idea behind TIL therapy is to use these tumor-fighting cells as a treatment.

In the trials provided, TIL cells are described as a cell therapy product given by intravenous infusion (through a vein). One investigational version is called Meta10-TIL, described as “metabolically armed” TIL therapy for people with advanced solid tumors.

[1]

Which clinical trials and cancers are being studied?

The provided trial data includes TIL-based approaches in several cancer settings:

  • Advanced solid tumors: An open-label study evaluates the safety and signs of benefit of Meta10-TIL therapy in advanced solid tumors.

  • Metastatic melanoma: A phase I/II, single-center study (ACTME) evaluates TIL therapy together with nivolumab, and later the combination of TIL plus low-dose PEG-IFNα plus nivolumab, for progressive unresectable stage III or stage IV melanoma.

  • Ovarian carcinoma: A phase I/II trial (OVACURE-2) studies adoptive T cell therapy (using TIL cells) plus low-dose IL-2 as a first-line neoadjuvant strategy in stage III/IV epithelial high-grade ovarian, fallopian tube, or primary peritoneal cancer.

[1][2][3]

How TIL therapy is given in these studies

Across the trials, the TIL product is given as an infusion into a vein.

  • Meta10-TIL for advanced solid tumors: Participants receive nonmyeloablative lymphodepletion chemotherapy (a pre-treatment that reduces immune cells without fully wiping out bone marrow function) with cyclophosphamide and fludarabine, followed by Meta10-TIL infusion on day 0.

  • ACTME in metastatic melanoma: The study evaluates safety and toxicity of TIL and nivolumab first, and later the combination of TIL, PEG‑IFNα, and nivolumab.

  • OVACURE-2 in ovarian cancer: The study evaluates TIL-based adoptive T cell therapy plus low-dose IL-2, and aims to determine dosing for phase II based on dose-limiting toxicities (DLTs).

[1][2][3]

What outcomes are measured (safety and effectiveness)

Safety outcomes

A central goal in these studies is to understand side effects. Trials measure adverse events (AEs) and grade them with CTCAE (a standard scale for severity).

  • In the Meta10-TIL advanced solid tumor study, the primary outcome is adverse events graded by NCI CTCAE v5.0 over 1 year after infusion.

  • In ACTME metastatic melanoma, safety and toxicity are evaluated using CTCAE 4.0, and certain grade 3 toxicities and serious adverse events may be considered acceptable if they do not lead to stopping treatment.

  • In OVACURE-2 ovarian cancer, toxicity related to TIL plus low-dose IL-2 is assessed using NCI CTCAE v5.0, with a focus on grade greater than III and identifying DLTs to help choose a recommended dose for phase II.

[1][2][3]

Effectiveness outcomes

These trials also look for signs the treatment may control cancer. Common measures include:

  • Objective response rate (ORR): The percent of patients with a confirmed partial response (PR) or complete response (CR), often measured with RECIST v1.1.

  • Duration of response (DOR): How long a PR or CR lasts before the cancer grows or the patient dies.

  • Progression-free survival (PFS): Time until the cancer progresses or death occurs.

  • Overall survival (OS): Time from a defined study point (for example, infusion date) to death.

  • Disease control rate (DCR): Percent of patients with CR, PR, or stable disease (SD).

In the ACTME melanoma study, disease control is assessed with imaging such as CT and/or MRI using RECIST 1.1 and also immune-related response criteria (irRC), which are sometimes used in immunotherapy research to better capture immune-related patterns of tumor change.

[1][2]

Who may join these trials (common inclusion and exclusion themes)

Each study has its own detailed rules. From the provided trial text, common themes include confirming the cancer type and stage, showing the cancer can be measured (or tracked) in standard ways, and making sure general health is strong enough for intensive immunotherapy approaches.

Examples of inclusion requirements described in the provided trials

  • Confirmed diagnosis and stage (for example, metastatic melanoma stage III unresectable or stage IV; or epithelial high-grade ovarian/fallopian tube/primary peritoneal cancer stage III/IV).

  • Measurable disease using RECIST v1.1 (some ovarian cancer participants may also qualify via elevated CA125 criteria as described).

  • Functional status requirements such as WHO performance status ≤ 1 or ECOG performance status 0–1, meaning the person is fairly active and able to care for themselves.

  • Laboratory values in acceptable ranges (blood counts and organ function measures), and negative viral testing for infections such as HIV, hepatitis B, and hepatitis C as specified.

Examples of exclusion considerations described in the provided trials

  • Pregnancy or breastfeeding.

  • Some forms of serious heart disease, such as NYHA Class III or IV.

  • Active serious infections requiring antibiotics.

  • Active immunodeficiency or autoimmune disease requiring immune-suppressing drugs (with vitiligo specifically noted as not excluding participation in these trials).

  • Brain metastases limitations differ by study: the melanoma trial allows brain metastases only if neurologically stable for at least 2 months and without dexamethasone; the ovarian trial excludes brain metastases.

[2][3]

Immune tests and biomarkers studied

Beyond tumor measurements and side effects, some trials include detailed immune research to understand why some patients respond better than others.

  • The metastatic melanoma ACTME trial includes goals such as building a possible biomarker profile, comparing immune features in patients with and without response, and studying the infused T cell product using immunomonitoring. It also describes evaluating immune characteristics in PBMCs (blood immune cells) and exploring differences between CD8-rich and CD8-poor metastases, including using CD8-immunoPET/CT methods as described in the trial record.

  • The ovarian cancer OVACURE-2 trial lists secondary objectives including immune monitoring with TCR clonotypes and tracking immune cell subsets such as CD8/CD4 and other immune cell categories named in the protocol summary.

  • The Meta10-TIL advanced solid tumor trial includes plans to characterize pharmacokinetic (PK) and pharmacodynamic (PD) profiles, which broadly means tracking the therapy in the body over time and its biological effects.

[1][2][3]
Topic What the trials show
Drug/therapy studied TIL cells (tumor-infiltrating lymphocytes), including Meta10-TIL (metabolically armed TIL)
Cancers studied Advanced solid tumors; metastatic melanoma; stage III/IV epithelial high-grade ovarian/fallopian tube/primary peritoneal cancer
How TIL therapy is given Intravenous infusion; one trial uses lymphodepletion chemotherapy (cyclophosphamide + fludarabine) before infusion
Combination approaches TIL + nivolumab; TIL + low-dose PEG‑IFNα + nivolumab; adoptive T cell therapy + low-dose IL‑2
Main safety measurement Adverse events graded with CTCAE (v4.0 or v5.0), including dose-limiting toxicities in dose-finding work
Main effectiveness measurements ORR, DOR, PFS, OS, disease control rate; responses assessed by RECIST v1.1 (and sometimes irRC)
Follow-up time mentioned Up to 1 year post infusion in the advanced solid tumor Meta10-TIL trial
Extra research questions Immune monitoring, biomarker profiles, and correlations between immune markers and clinical response

FAQ

  • What are TIL cells? TIL cells are T cells (a type of white blood cell) that are found inside a tumor. In these trials, the cells are collected from tumor tissue, prepared and expanded (grown to larger numbers) in a lab, and then infused back into the patient through a vein to help attack cancer cells.
  • Which cancers are being studied with TIL cells in these trials? The trials study TIL-based therapy in advanced solid tumors, metastatic melanoma (stage III unresectable or stage IV), and epithelial high-grade ovarian, fallopian tube, or primary peritoneal cancer at FIGO stage III or IV.
  • How is TIL treatment given in these studies? TIL cells are given by intravenous infusion. In one study for advanced solid tumors, patients first receive lymphodepletion chemotherapy (cyclophosphamide and fludarabine) before the TIL infusion. Other trials combine TIL therapy with medicines such as nivolumab, low-dose peginterferon alfa (PEG‑IFNα), or low-dose IL‑2.
  • What are the main goals researchers measure in these trials? A main goal is safety, measured by the number and severity of adverse events (side effects) using CTCAE grading. Trials also measure cancer outcomes such as objective response rate (tumor shrinkage), duration of response, progression-free survival (time until the cancer grows or a person dies), overall survival, and disease control rate (stable disease, partial response, or complete response).
  • What kinds of tests or assessments might participants go through? Based on the trial descriptions, participants may have physical exams and imaging tests like CT or MRI to measure tumors using RECIST criteria. Some trials also include immune monitoring (checking immune markers) and may study biomarker profiles to understand which patients respond better.

Ongoing Clinical Trials on TIL CELLS

  • Study of TIL therapy combined with peginterferon alfa-2a and nivolumab for patients with metastatic melanoma

    Recruiting

    1 1 1
    Investigated drugs:
    The Netherlands

  • Study of Tumor-Infiltrating Lymphocyte Cell Therapy and Aldesleukin for Patients with Advanced Stage Ovarian Cancer as Initial Treatment

    Not yet recruiting

    1 1 1
    Investigated drugs:
    The Netherlands

Glossary

  • TIL cells (Tumor-Infiltrating Lymphocytes): Immune cells (T cells) that are naturally present inside a tumor. In these trials, they are collected from tumor tissue, multiplied in a lab, and infused back into the patient to help fight cancer.
  • Adoptive T cell therapy (ACT): A treatment approach where a patient receives immune cells (T cells) that have been prepared outside the body and then given back by infusion. TIL therapy is one type of adoptive T cell therapy.
  • Meta10-TIL (Metabolically Armed TIL): A specific investigational form of TIL therapy being studied in advanced solid tumors. “Metabolically armed” means the product is designed to support how the cells use energy and function, but the trial is focused on learning safety and possible benefit.
  • Intravenous infusion: Giving a treatment directly into a vein, usually through an IV line.
  • Open-label study: A study where both the patient and the research team know what treatment is being given.
  • Lymphodepletion chemotherapy: Chemotherapy given before TIL infusion to lower the number of existing immune cells, which can help the infused TIL cells expand and work better. In one trial this uses cyclophosphamide and fludarabine.
  • Cyclophosphamide: A chemotherapy medicine used in some TIL protocols as part of lymphodepletion (pre-treatment) before the TIL infusion.
  • Fludarabine: A chemotherapy medicine used in some TIL protocols as part of lymphodepletion before TIL infusion.
  • Nivolumab: An immunotherapy drug studied in combination with TIL therapy in metastatic melanoma in the provided trial data.
  • PEG-IFNα (Peginterferon alfa): A type of interferon medicine that affects the immune system. In one melanoma study it is used at low dose together with TIL therapy and nivolumab.
  • IL-2ld (Low-dose IL-2): A low dose of interleukin-2, an immune-signaling protein. In one ovarian cancer study it is combined with adoptive T cell therapy to evaluate safety and dosing.
  • Adverse event (AE): Any unwanted medical problem that happens during a study, whether or not it is clearly caused by the study treatment.
  • CTCAE (Common Terminology Criteria for Adverse Events): A standard system used in clinical trials to grade side effects by severity. The trials listed use CTCAE version 4.0 or 5.0.
  • Dose-limiting toxicity (DLT): A side effect serious enough to limit how much of a treatment can be given. DLTs help researchers choose the recommended dose for later study phases.
  • Objective Response Rate (ORR): The percentage of participants whose tumors shrink by a defined amount. ORR usually includes complete response and partial response.
  • Complete Response (CR): No signs of cancer seen on scans based on the study’s response rules.
  • Partial Response (PR): A meaningful decrease in tumor size on scans, but not complete disappearance.
  • Stable Disease (SD): Cancer that is not clearly shrinking but also not clearly growing during the study period.
  • Disease Control Rate (DCR): The percentage of participants who have stable disease, partial response, or complete response.
  • Duration of Response (DOR): How long a response (such as a partial or complete response) lasts before the cancer grows again or the patient dies.
  • Progression-Free Survival (PFS): The time from treatment start (or a defined study point) until the cancer grows (progresses) or the patient dies from any cause.
  • Overall Survival (OS): The time from a defined study point (for example, the TIL infusion date) until death.
  • RECIST v1.1: A standardized set of rules for measuring tumors on imaging (like CT or MRI) and deciding if cancer has responded, stayed stable, or progressed.
  • Immune-related response criteria (irRC): Response rules used in some immunotherapy studies to better capture how tumors may behave when the immune system is stimulated.
  • Pharmacokinetics (PK): How a therapy moves through and is present in the body over time. In a cell therapy study, PK may describe how long infused cells can be detected.
  • Pharmacodynamics (PD): What the therapy does to the body, such as immune changes after cell infusion.
  • Biomarker: A measurable sign (in blood, tumor tissue, or imaging) that may help predict response or side effects.
  • Immune monitoring / immunomonitoring: Testing that tracks immune system changes during the study, such as features of infused T cells or immune cells in blood.
  • PBMCs (Peripheral Blood Mononuclear Cells): A group of immune cells in the blood (including lymphocytes and monocytes) often used for immune testing in clinical studies.
  • TCR clonotypes: Patterns of T-cell receptors (TCRs) that show how many different T-cell “families” are present. Tracking clonotypes can show whether certain T cells expand after treatment.
  • CD8-rich / CD8-poor metastases: Descriptions of tumor spread (metastases) with many CD8 T cells (CD8-rich) or few CD8 T cells (CD8-poor). CD8 T cells are immune cells that can directly kill cancer cells.
  • CT scan / MRI: Imaging tests used to look at tumor size and changes over time.
  • Advanced solid tumors: Cancers that form solid masses (not blood cancers) and are at an advanced stage, often meaning they have spread or cannot be removed completely with surgery.
  • Metastatic melanoma: Melanoma (skin cancer) that has spread beyond the original site. In the provided trial, it includes unresectable stage III or stage IV disease.
  • Neoadjuvant therapy: Treatment given before the main planned treatment (often surgery). In the ovarian cancer trial, the approach is studied as a first-line neoadjuvant strategy.
  • ECOG / WHO performance status: Scales that describe how well a person can do daily activities. Lower numbers (like 0 or 1) mean the person is more active and generally better able to handle treatment.
  • NYHA Class III/IV: A classification for heart failure severity. Class III/IV means more severe symptoms and is used as an exclusion criterion in these trials.

References

  1. https://clinicaltrials.gov/study/NCT07106814
  2. https://clinicaltrials.eu/trial/study-on-the-safety-of-til-cells-peginterferon-alfa-2a-and-nivolumab-for-patients-with-metastatic-melanoma/
  3. https://euclinicaltrials.eu/search-for-clinical-trials/?lang=en&ctrId=2025-522659-24-00