Immunotherapy with TIL for Cancer

Recruiting at 1 trial location

Overseen By NCI/Surgery Branch Recruitment Center

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: Steroids, Investigational agents

Disqualifiers: Pregnancy, Infections, Autoimmune, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 4

Duration: 4 weeks

332 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new immunotherapy treatment that uses a patient's own white blood cells, known as Tumor Infiltrating Lymphocytes (TIL), to combat cancer. Researchers aim to determine if these specially selected cells can shrink tumors in individuals with digestive tract, urothelial, breast, or ovarian/endometrial cancers. The trial also seeks to ensure the treatment's safety. It is suitable for adults with these cancer types that have not responded to standard chemotherapy and have a tumor that can be safely removed for TIL production. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications, but it mentions that patients must have completed any prior systemic therapy at the time of enrollment. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that TIL therapy, which uses special immune cells from tumors, has potential in treating cancers like melanoma and lung cancer. Researchers have tested it in over 200 melanoma patients. Studies have found that TIL therapy generally causes manageable side effects, mostly from chemotherapy and a drug called high-dose aldesleukin, which are part of the treatment.

When combined with pembrolizumab, a drug that boosts the immune system, TIL therapy continues to show promise. However, the side effects remain similar, mainly due to the chemotherapy and aldesleukin used with the TILs.

Although researchers are still studying TIL therapy, its presence in a later phase of research suggests some confidence in its safety. However, discussing any concerns with a healthcare provider before joining a trial is important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the treatment using young Tumor-Infiltrating Lymphocytes (TIL) for cancer because it offers a new way to harness the immune system. Unlike traditional cancer therapies like chemotherapy or radiation that target the cancer cells directly, TIL therapy involves extracting and multiplying the patient's own immune cells to fight the tumor. This approach is combined with pembrolizumab, an immune checkpoint inhibitor, which can enhance the immune response. The combination of these immune-based treatments could potentially lead to more effective and durable responses in patients with advanced cancers, offering hope for those who haven't responded well to standard treatments.

What evidence suggests that this trial's treatments could be effective for cancer?

Research has shown that Tumor Infiltrating Lymphocyte (TIL) therapy holds promise for treating various solid tumors. In earlier studies, 80% of patients who received TIL therapy experienced either stabilization or improvement in their cancer, with 8 out of 10 patients seeing positive results. Additionally, about 36% of patients saw a significant decrease in tumor size. In this trial, some participants will receive TIL therapy combined with pembrolizumab, a drug that boosts the immune system, potentially enhancing results by helping the body attack cancer cells more effectively. These findings suggest TIL therapy could be effective for cancers of the digestive tract, bladder, breast, or ovaries/uterus. ^{3 5 6 7 8}

Who Is on the Research Team?

Steven A Rosenberg, M.D.

Principal Investigator

National Cancer Institute (NCI)

Are You a Good Fit for This Trial?

Adults aged 18-72 with certain types of metastatic cancer (digestive tract, breast, ovarian/endometrial, etc.) who haven't responded to standard treatments. Participants must not have HIV or hepatitis, agree to birth control and testing if applicable, and be in relatively good health otherwise.

Inclusion Criteria

You do not have HIV, hepatitis B, or hepatitis C in your blood.

Certain blood and chemistry test results must meet specific requirements.

My cancer is metastatic and falls into one of the specified categories.

Exclusion Criteria

I do not have any active infections, bleeding disorders, or serious illnesses.

My lung function (FEV1) is 50% or less.

I am on steroids, but only because my brain cancer requires it.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Work up stage

Patients undergo history and physical examination, scans, x-rays, lab tests, and other tests as needed

1-2 weeks

1-2 visits (in-person)

Surgery

Patients undergo surgery to remove a tumor for TIL product growth

1 week

1 visit (in-person)

Leukapheresis

Patients may undergo leukapheresis to obtain additional white blood cells

1 day

1 visit (in-person)

Treatment

Patients receive conditioning chemotherapy, TIL cells, and aldesleukin, and stay in the hospital for about 4 weeks

4 weeks

Inpatient stay

Follow-up

Patients return to the clinic for physical exams, review of side effects, lab tests, and scans every 1-3 months for the first year, then every 6 months to 1 year

Up to 2 years

Multiple visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Young TIL

Trial Overview

The trial is testing a therapy where white blood cells from the patient's tumor are grown in large numbers and reinfused into them. The study aims to see if these Tumor Infiltrating Lymphocytes (TIL) can shrink tumors effectively and safely.

How Is the Trial Designed?

Group I: 5/Unselected TIL + Pembro Prior to Cells Experimental Treatment 5 Interventions

Non-myeloablative, lymphodepleting preparative regimen of cyclophosphamide and fludarabine + young unselected TIL + high-dose aldesleukin + pembrolizumab prior to cell administration and 3 additional doses every 3 weeks following cell infusion

Group II: 4/Unselected TIL + Pembro at POD Experimental Treatment 5 Interventions

Non-myeloablative, lymphodepleting preparative regimen of cyclophosphamide and fludarabine + young unselected TIL + high-dose aldesleukin + pembrolizumab within 4 weeks of progressive disease for up to 8 doses every 3 weeks

Group III: 3/Unselected TIL + Pembro Prior to Cells Experimental Treatment 5 Interventions

Non-myeloablative, lymphodepleting preparative regimen of cyclophosphamide and fludarabine + young unselected TIL + high-dose aldesleukin + pembrolizumab prior to cell administration and 3 additional doses every 3 weeks following cell infusion

Group IV: 2/Unselected TIL (CLOSED) Experimental Treatment 4 Interventions

Non-myeloablative, lymphodepleting preparative regimen of cyclophosphamide and fludarabine + young unselected TIL + high-dose aldesleukin (CLOSED)

Group V: 1/CD8+ Enriched TIL (CLOSED) Experimental Treatment 4 Interventions

Non-myeloablative, lymphodepleting preparative regimen of cyclophosphamide and fludarabine + young CD8+ enriched TIL + high-dose aldesleukin (CLOSED)

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Autologous tumor-infiltrating lymphocyte (TIL) therapy has shown strong and consistent clinical responses in metastatic melanoma patients across various clinical trials, indicating its potential as a significant treatment option even alongside newer therapies.

The review discusses important aspects of TIL therapy, including the use of lymphodepleting regimens and interleukin-2 (IL-2), highlighting both the efficacy and associated toxicity, as well as future strategies for improving TIL production and application in other cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adoptive transfer of tumor-infiltrating lymphocytes in melanoma: a viable treatment option. Rohaan, MW., van den Berg, JH., Kvistborg, P., et al.[2019]

In a study of 10 patients with advanced melanoma treated with autologous tumor-infiltrating lymphocytes (TILs) and interleukin-2 (IL-2), no serious adverse effects were reported, indicating a favorable safety profile for this immunotherapy approach.

Among the patients, there were instances of complete and partial remission, with one patient surviving for 9 years post-treatment, suggesting potential long-term benefits; however, the presence of certain T cell types was associated with shorter overall survival, highlighting the need for further research into optimizing treatment combinations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adoptive Cell Therapy with Tumor-Infiltrating Lymphocytes in Advanced Melanoma Patients. Saint-Jean, M., Knol, AC., Volteau, C., et al.[2021]

Tumor-infiltrating lymphocytes (TILs) are a promising treatment for solid tumors, as they are derived from the patient's own body and have fewer adverse reactions compared to genetically modified therapies.

Despite their potential, the effectiveness of TIL therapy is currently limited by challenges in the immune microenvironment and antigen mutations, which the article reviews in terms of enhancing their therapeutic impact.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tumor-infiltrating lymphocytes: Warriors fight against tumors powerfully. Lin, B., Du, L., Li, H., et al.[2021]

Tumor-infiltrating lymphocytes (TIL) expanded from tumors treated with a collagen matrix and recombinant human IL-6 (rIL-6) showed significantly enhanced antitumor efficacy compared to TIL from other treatment conditions in five separate experiments.

This study suggests that increasing local concentrations of cytokines like rIL-6 at tumor sites can improve the potency of TIL, potentially leading to more effective cancer therapies in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The use of interleukin-6 to generate tumor-infiltrating lymphocytes with enhanced in vivo antitumor activity. Marcus, SG., Perry-Lalley, D., Mulé, JJ., et al.[2019]

In a study involving 55 patients with various cancers, including melanoma, renal cell carcinoma, and colorectal cancer, only one patient showed an objective tumor response, indicating limited efficacy of tumor-infiltrating lymphocytes (TIL) as a treatment.

Patients receiving a higher dose of TIL (mean = 54.4 x 10^9) had a median survival of 11.8 months, suggesting a potential dose/benefit relationship, although overall response rates were not encouraging.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tumor-infiltrating lymphocytes and interleukin-2: dose and schedules of administration in the treatment of metastatic cancer. Dillman, R., Schiltz, P., DePriest, C., et al.[2006]

A simplified method for generating CD8+ enriched 'young' tumor-infiltrating lymphocytes (TIL) was successfully established, allowing for treatment of 33 melanoma patients, with 58% showing an objective response after therapy.

The study demonstrated that this approach could lead to significant clinical responses, including complete regression in some patients, suggesting it could be a viable option for advanced melanoma treatment without the need for individualized tumor-reactivity screening.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CD8+ enriched "young" tumor infiltrating lymphocytes can mediate regression of metastatic melanoma. Dudley, ME., Gross, CA., Langhan, MM., et al.[2021]

In a study using both immune-deficient nude mice and normal A/J mice, the use of anti-PD-1 and anti-PD-L1 antibodies effectively suppressed tumor growth in A/J mice, highlighting the critical role of T lymphocytes in the antitumor immune response.

The research found that increased infiltration of activated CD8+ tumor-infiltrating lymphocytes (TILs) was associated with smaller tumor sizes, suggesting that enhancing CD8+ TIL infiltration could be a promising strategy for treating neuroblastoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CD69 on Tumor-Infiltrating Cells Correlates With Neuroblastoma Suppression by Simultaneous PD-1 and PD-L1 Blockade. Inoue, S., Takeuchi, Y., Horiuchi, Y., et al.[2023]

In a study of 38 patients with anal squamous cell carcinoma, high levels of CD3+ and CD4+ tumor-infiltrating lymphocytes (TILs) were associated with better survival rates, indicating their potential as positive prognostic factors.

Conversely, high numbers of granzyme B+ cytotoxic TILs were linked to poorer outcomes, suggesting that these cells may be associated with therapy-resistant tumor clones, while regulatory T cells (Treg) did not show any significant prognostic impact.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tumor-infiltrating cytotoxic T cells but not regulatory T cells predict outcome in anal squamous cell carcinoma. Grabenbauer, GG., Lahmer, G., Distel, L., et al.[2020]

Tumor infiltrating lymphocytes (TIL) are becoming important in immunotherapy, and their effectiveness can be enhanced through various augmentation methods, both in vitro and in vivo.

The article discusses a specific technique called cyclophosphamide immunopriming, which is used to enhance TILs before they are applied in therapeutic protocols, potentially improving their ability to fight tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunopriming of tumor infiltrating lymphocytes with neoadjuvant cyclophosphamide. Guinan, P., Shaw, M., Rubenstein, M.[2019]

Immunotherapy using tumor-infiltrating lymphocytes (TIL) activated with interleukin 2 (IL2) has shown promise in treating metastatic melanoma and renal cell carcinoma, with some patients experiencing complete or partial responses.

Despite the optimism surrounding TIL therapy, the current understanding of its antitumor mechanisms and the effects of systemic administration is still limited, highlighting the need for further clinical trials and research to optimize this treatment approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cancer therapy with tumor-infiltrating lymphocytes: evaluation of potential and limitations. Whiteside, TL.[2004]

Adoptive cell therapy using autologous tumor infiltrating lymphocytes (TIL) has shown promising results, with objective response rates of up to 52% in patients with advanced metastatic melanoma.

The treatment involves activating and expanding TILs outside the body before re-infusing them into the patient, followed by administration of Interleukin-2 (IL-2) to enhance the immune response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Key Factors in Clinical Protocols for Adoptive Cell Therapy in Melanoma. Considine, B., Hurwitz, ME.[2023]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC9455018/

Tumor Infiltrating Lymphocyte (TIL) Therapy for Solid ...

Patients received a mean number of TILs of 2.73 × 1010, and the disease control rate (DCR) was 80%, the ORR was 36%, the CR was 3%, and the PR was 33%.

2.

astctjournal.org

astctjournal.org/article/S2666-6367(24)00783-8/fulltext

Tumor-Infiltrating Lymphocyte Therapy: A New Frontier

This review provides a summary of the latest advances in TIL therapy and what lies ahead for the field.

3.

bmjoncology.bmj.com

bmjoncology.bmj.com/content/4/1/e000566

Tumour-infiltrating lymphocyte therapy landscape

Tumour-infiltrating lymphocyte (TIL) therapy has emerged as a promising adoptive cell transfer strategy for solid tumours.

4.

frontiersin.org

frontiersin.org/journals/immunology/articles/10.3389/fimmu.2025.1601773/full

Tumor-infiltrating lymphocytes in cancer immunotherapy

This review explores the phenotypic and functional diversity of TILs—including CD8+ cytotoxic T cells, CD4+ helper T cells, regulatory T cells, B cells, and ...

5.

clinicaltrials.gov

clinicaltrials.gov/study/NCT01174121

NCT01174121 | Immunotherapy Using Tumor Infiltrating ...

The purpose of this study is to see if these specifically selected tumor fighting cells can cause digestive tract, urothelial, breast, or ovarian/endometrial ...

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC10840042/

Efficacy and safety of autologous tumor-infiltrating ...

Tumor-infiltrating lymphocyte (TIL) therapy has shown efficacy in metastatic melanoma, non-small cell lung cancer, and other solid tumors.

7.

annalsofoncology.org

annalsofoncology.org/article/S0923-7534(25)00135-8/fulltext

Safety of adoptive therapy with tumor-infiltrating ...

TIL-ACT presents a safe and manageable toxicity profile, with most toxicities arising from chemotherapy and HD-IL-2. •. Further studies with ...

8.

cell.com

cell.com/cell-reports-medicine/fulltext/S2666-3791(25)00089-8

Safety and efficacy of combined treatment with tumor- ...

Tumor-infiltrating lymphocytes (TILs) are effective in the treatment of metastatic melanoma (MM), but toxicity limits its application.