Adoptive Cell Transfer + Interleukin 2 for Cancer

Overseen By Catherine O'neil

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Gregory Daniels

Must be taking: Interleukin-2

Must not be taking: Immune suppressants

Disqualifiers: Pregnancy, Infections, Heart disease, others

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

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether special tumor-fighting cells, taken from a participant's own tumor and enhanced in a lab, can effectively combat cancer. These cells, known as Autologous Tumor Infiltrating Lymphocytes (or TIL Therapy), are administered alongside a protein called Interleukin 2, which boosts the immune response. The trial targets individuals with specific cancers, such as head and neck cancer or melanoma, who have tried other treatments without success and have stable or progressing disease. Participants should not have more than three brain metastases, and any significant brain lesions must remain stable for three months after treatment. This study could offer a new option for those who have exhausted other therapies. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative therapy.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, it mentions that more than four weeks must have passed since any prior systemic therapy, and six weeks since any anti-CTLA4 therapy, suggesting a possible need to pause certain treatments.

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

Research has shown that using a patient's own immune cells, as in lifileucel therapy, remains safe over the long term, with no major issues reported in five years. Patients have benefited from this treatment without new safety concerns.

High-dose interleukin 2 (IL-2) is an FDA-approved treatment for certain cancers, such as advanced kidney cancer. Studies have demonstrated its safety for humans. While it can cause side effects, doctors know how to manage them.

In summary, studies have proven both treatments safe, though they may have some side effects. These treatments help the body fight cancer. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about using autologous tumor infiltrating lymphocytes (TILs) with high-dose interleukin 2 for cancer because this approach harnesses the patient's own immune system to fight the disease. Unlike traditional treatments like chemotherapy or radiation, which attack cancer cells but can also harm healthy cells, TIL therapy specifically targets the tumor cells. This method involves extracting immune cells from the tumor, expanding them in the lab, and then reinfusing them into the patient to boost their natural cancer-fighting ability. Additionally, high-dose interleukin 2 is used to stimulate these immune cells further, potentially leading to a more effective and targeted attack on the cancer. This personalized and precise approach is what makes it stand out from conventional cancer therapies.

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

Research has shown that using a person's own immune cells, called tumor-infiltrating lymphocytes (TIL), holds promise for treating solid tumors. In this trial, participants will receive TIL therapy, which has demonstrated particular effectiveness for melanoma, with mixed results for other cancer types. Additionally, participants will receive high-dose interleukin 2 (IL-2), an important treatment for advanced solid tumors, such as metastatic kidney cancer. IL-2 has sometimes led to a complete response, where the cancer entirely disappears. These treatments boost the body's immune system to fight cancer, offering hope for those with difficult-to-treat tumors. ^{2 3 4 5 6}

Who Is on the Research Team?

Ezra Cohen, MD

Principal Investigator

University of California, San Diego

Gregory Daniels, MD

Principal Investigator

University of California, San Diego

Are You a Good Fit for This Trial?

This trial is for adults with advanced melanoma or head and neck cancers that can't be removed by surgery, have progressed after treatment, and are not candidates for curative therapy. They must have a life expectancy over 3 months, no HIV or hepatitis B/C, good organ function, and an ECOG status of 0-1 (fully active to restricted in physically strenuous activity). Pregnant women and those with primary immunodeficiency or certain heart conditions cannot participate.

Inclusion Criteria

My head or neck cancer has returned or spread.

It has been over four weeks since my last systemic therapy.

I have up to 3 brain metastases that are stable and treated if needed.

Exclusion Criteria

I have a condition that significantly weakens my immune system.

I need medication to suppress my immune system, including steroids.

I am pregnant or breastfeeding.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Lymphodepletion

Participants undergo lymphodepletion to suppress the immune system before cell transfer

1-2 weeks

Adoptive Cell Transfer

Participants receive infusions of autologous tumor infiltrating lymphocytes and high-dose interleukin-2

1 week

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Autologous Tumor Infiltrating Lymphocytes
• High-Dose Interleukin 2

Trial Overview The study tests if tumor fighting cells from the patient's own tumors can combat cancer when reintroduced into their body alongside high-dose interleukin-2 (IL-2), which supports immune response. This adoptive cell transfer aims to see if these lab-grown cells help fight the cancer more effectively.

How Is the Trial Designed?

Group I: Solid Tumor Experimental Treatment 2 Interventions

Solid Tumor

Autologous Tumor Infiltrating Lymphocytes is already approved in United States for the following indications:

Approved in United States as Lifileucel for:

• Advanced melanoma

Who Is Running the Clinical Trial?

Gregory Daniels

Lead Sponsor

Trials

2

Recruited

30+

Immunotherapy Foundation

Collaborator

Trials

1

Recruited

20+

Published Research Related to This Trial

In a study involving 69 patients with metastatic melanoma, unselected young tumor-infiltrating lymphocytes (TILs) showed a higher response rate (35%) compared to CD8(+)-enriched TILs (20%), although the difference was not statistically significant.

The research suggests that unselected young TILs may be more effective and easier to prepare than CD8(+)-enriched TILs, as the latter did not demonstrate superior therapeutic potency despite being more complex to produce.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized selection design trial evaluating CD8+-enriched versus unselected tumor-infiltrating lymphocytes for adoptive cell therapy for patients with melanoma. Dudley, ME., Gross, CA., Somerville, RP., et al.[2021]

In a study involving 28 patients with various cancers, including malignant melanoma and renal cell carcinoma, treatment with autologous expanded tumor-infiltrating lymphocytes (TIL) combined with interleukin-2 resulted in objective tumor responses in 29% of renal cell cancer patients and 23% of melanoma patients, lasting between 3 to 14 months.

The treatment was associated with limited toxic side effects, and notably, no patients required intensive-care monitoring, suggesting a favorable safety profile for this immunotherapy approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tumour-infiltrating lymphocytes and interleukin-2 in treatment of advanced cancer. Kradin, RL., Kurnick, JT., Lazarus, DS., et al.[2020]

In a phase I/II trial involving 25 patients with treatment-refractory metastatic melanoma, adoptive cell transfer therapy using tumor-infiltrating lymphocytes (TIL) combined with a lower-dose IL2 regimen resulted in a 42% overall response rate, including three complete responses and seven partial responses.

The study demonstrated that while some classical IL2-related toxicities occurred, they were manageable outside of intensive care, suggesting that this attenuated IL2 approach may enhance safety while still achieving significant clinical efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-Lasting Complete Responses in Patients with Metastatic Melanoma after Adoptive Cell Therapy with Tumor-Infiltrating Lymphocytes and an Attenuated IL2 Regimen. Andersen, R., Donia, M., Ellebaek, E., et al.[2021]

In a pilot study involving 6 patients with metastatic melanoma, the combination of tumor-infiltrating lymphocyte (TIL) therapy and low-dose IL-2 injections resulted in significant reductions in treatment-related toxicity, with no severe adverse events reported.

The treatment led to objective clinical responses in 2 patients, with ongoing complete responses lasting over 10 months, suggesting that low-dose IL-2 can enhance the safety and efficacy of adoptive cell therapy for melanoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adoptive cell therapy with autologous tumor infiltrating lymphocytes and low-dose Interleukin-2 in metastatic melanoma patients. Ellebaek, E., Iversen, TZ., Junker, N., et al.[2021]

Adoptive cell therapy using autologous tumor-infiltrating lymphocytes (TIL) combined with high-dose interleukin-2 (IL-2) showed promising results, with 50% of refractory metastatic melanoma patients experiencing tumor regression, highlighting its efficacy.

The modified 'Young'-TIL protocol, which uses minimally cultured T cells without extensive selection, resulted in a higher patient retention rate and better clinical responses compared to the 'Selected'-TIL protocol, suggesting it may be a more feasible and effective treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Minimally cultured or selected autologous tumor-infiltrating lymphocytes after a lympho-depleting chemotherapy regimen in metastatic melanoma patients. Besser, MJ., Shapira-Frommer, R., Treves, AJ., et al.[2013]

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]

In a study involving 21 cancer patients, tumor-infiltrating lymphocytes (TIL) were successfully activated with interleukin 2 (IL-2) and showed significant tumor-killing activity, leading to complete regression of malignant pleural effusions in one pancreatic cancer patient and nearly complete regression of malignant ascites in a gastric cancer patient.

The optimal concentration of IL-2 for maximizing TIL proliferation and tumor-killing ability was found to be 1,500 IU/ml, demonstrating that adoptive transfer of activated TIL can be an effective immunotherapy approach in treating certain cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Clinical application of adoptive immunotherapy by cytotoxic T lymphocytes induced from tumor-infiltrating lymphocytes]. Yamaue, H., Tanimura, H., Tsunoda, T., et al.[2011]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36600653/

Efficacy and safety of lifileucel, a one-time autologous tumor ... Herein, we report independent review committee (IRC)-assessed outcomes of 153 patients treated with lifileucel in a large multicenter Phase 2 cell therapy trial ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO-25-00765

Long-Term Efficacy and Safety of Lifileucel Tumor ... This 5-year analysis demonstrated long-term benefit and meaningful OS with one-time lifileucel therapy, with no additional long-term safety concerns.

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1040842825000599

Outcomes of tumor-infiltrating lymphocyte therapy in solid ... According to the study's findings, TIL therapy is effective in treating solid tumors, especially melanoma, but its results vary according to the kind of cancer ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12482274/

Novel tumor-infiltrating lymphocytes therapy in solid tumors This report summarizes the latest updates on TIL monotherapies and combination regimens for solid tumors from the 2025 ASCO Annual Meeting, ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT03645928

NCT03645928 | Study of Autologous Tumor Infiltrating ... The adoptive cell transfer therapy used in this study involves patients receiving a nonmyeloablative (NMA) lymphodepletion regimen, followed by infusion of ...

6. sciencedirect.com sciencedirect.com/science/article/pii/S0147027225000790

Current perspectives on Lifileucel tumor-infiltrating ... TIL treatment seeks to activate the body's immune system to elicit a vigorous anti-tumor response, perhaps resulting in tumor shrinkage and improved patient ...