How TIL therapy can fight solid tumors like melanoma

Oct 05, 2022
Devin Golden

How TIL therapy can fight solid tumors like melanoma

Certain lymphocytes are called tumor-infiltrating lymphocytes, and they might be the source of a type of cancer cell and gene therapy.

A major part of cancer cell and gene therapy is modifying immune cells to make them capable of killing cancer cells. Most immune cells need genetic alterations to prepare them for the confrontation with resistant tumors.

However, some immune cells may already be strong enough to do this job without modifications. These cells are called tumor-infiltrating lymphocytes. Is there a way to hone in on these cells and amplify their importance in the battle against cancer?

Alliance for Cancer Gene Therapy has published a guide to tumor-infiltrating lymphocytes and TIL therapy, including some of the latest developments in using it to treat solid tumors. If you’d like to learn more about Alliance for Cancer Gene Therapy, please visit our “Who We Are” page to see why our mission is focused on advancing cell and gene therapy research and development to transform cancer treatment.

What are tumor-infiltrating lymphocytes?

Tumor-infiltrating lymphocytes, or TILs for short, are white blood cells that have migrated from the blood to the tumor. Additionally, they’ve successfully penetrated tumor cells and began chipping away at cancer.

TILs can be T cells or B cells, and they are candidates for transformation into a cancer therapy called TIL therapy.

What is TIL therapy?

TIL therapy involves removing these tumor-infiltrating cells and amplifying them to create billions more, all with the same original and successful anti-cancer traits. This is called adoptive cell transfer, and it’s a main component of cell and gene therapy. 

In the case of TIL therapy, scientists remove TILs directly from the tumor, ensuring that they collect proficient immune cells for multiplication. 

Comparing TIL therapy and CAR T-cell therapy

TIL therapy is similar in some ways to another type of cell and gene therapy, CAR T-cell therapy. Both use the patient’s own immune cells to fight cancer.

The main difference is CAR T-cell therapy, short for chimeric antigen receptor T-cell therapy, requires scientists to modify T cells in a lab to make them more proficient against cancer. The U.S. Food and Drug Administration has approved six CAR T-cell therapies for various types of blood cancers. None have yet worked consistently or safely for solid tumors, though.

One of the main reasons for this slower progress in solid tumors is CAR T-cell therapies need a protein target – the CAR is an added protein receptor that directs the T cells to search for cancer cells with the associated protein. Blood cancer cells often have proteins that are not on healthy cells. Solid tumors usually have different cell types and share proteins with healthy tissue, making the development of effective CAR T-cell therapies much more challenging.

TIL therapy uses T cells that are already winning the battle against cancer. Rather than modifying these cells, scientists simply have to expand their numbers so that the immune system has more cells adept against cancer. This type of cancer cell therapy is promising since it doesn’t start from ground zero in the fight against cancer.

Using TIL therapy to treat cancer

Since TIL therapy uses cells that are already gaining ground in the battle with cancer, this type of cell therapy holds potential against solid tumors.

Amer Zureikat, MD, FACS, of the University of Pittsburgh School of Medicine, is an ACGT Research Fellow. He’s using grant funding from ACGT to explore using TIL therapy for pancreatic cancer. There are close to 60,000 new cases of pancreatic cancer in the U.S. each year, and the 5-year survival rate is a dismal 11%, which is the main reason why new therapeutic options like TIL therapy are needed to help patients.

Using TIL therapy for melanoma

Melanoma, a type of skin cancer diagnosed in close to 100,000 people in the U.S. each year, might be the solid tumor holding the greatest prospects for TIL therapy. This adoptive cell transfer has resulted in complete remission for 10-20% of melanoma patients in clinical trials. Michael Lotze, MD, chair of ACGT’s Scientific Advisory Council, published the data and called it “practice-changing results.”

Melanoma cells, like the ones above, might be targets of tumor-infiltrating lymphocytes.

Tumor-infiltrating lymphocytes was the featured therapy of a recent melanoma clinical trial in the Netherlands, as reported by NBC News and other outlets. The results were presented at the European Society of Medical Oncology Congress in Paris, on Sept. 10, 2022.

In the clinical study, 168 patients with metastatic melanoma received either TIL therapy or the current standard treatment, an immunotherapy drug called ipilimumab.

This treatment is given to patients who don’t respond to first-line treatment.

Ipilimumab is an immune checkpoint inhibitor that blocks two protein receptors from connecting: CTLA4 on T cells and B7 on cancer cells. The blocking of these two receptors keeps T cells alert for the presence of melanoma.

TIL therapy impressively outperformed ipilimumab in the trial:

  • 20% of patients receiving TIL therapy had a complete response, meaning their melanoma tumors disappeared.
  • Only 7% of patients receiving ipilimumab had a complete response.
  • The median survival from TIL therapy is more than two years, while ipilimumab led to a median survival of 1.5 years.

Next steps in supporting further TIL therapy development

This latest news regarding TIL therapy is more evidence that the scientific community is inching closer to finding cures for cancer. Improving survival rates for cancers like melanoma through the use of TIL therapy is a major step forward – and could save many lives.

Now is the time to keep the momentum going. ACGT asks you to join our Alliance of scientists, patients, biotech leaders and donors. The last group is the most important, as none of ACGT’s funding of innovative research programs would be possible without the support of our donors.

Please donate today to help ACGT support TIL therapy researchers and others who believe in cell and gene therapy as a potential cure for cancer. If you’ve enjoyed reading this latest news about cell and gene therapy, sign up for our monthly email newsletter to receive more updates directly to your inbox about this emerging field of cancer treatment.

Page sources

  1. New cell-based therapy for melanoma more effective than existing treatment, trial finds. NBC News. Retrieved from: https://www.nbcnews.com/health/cancer/new-cell-based-therapy-melanoma-effective-existing-treatment-trial-fin-rcna46935. Accessed: 09/14/2022.
  2. Efficacy of adoptive therapy with tumor-infiltrating lymphocytes and recombinant interleukin-2 in advanced cutaneous melanoma: a systematic review and meta-analysis. Annals of Oncology. Retrieved from: https://www.annalsofoncology.org/article/S0923-7534(20)32553-9/fulltext. Accessed: 10/03/2022.