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What is Tumor-Infiltrating Lymphocyte (TIL) Therapy?

November 2020

Immunotherapy

Immunotherapy is the practice of manipulating T cells to treat cancer. Also called adoptive cell therapies, there are multiple strategies used to combat different diseases in the body. Some methods, such as chimeric antigen receptor (CAR) T cell therapy and engineered T cell receptor (TCR) therapy, involve tampering with the receptors on the surface of T lymphocytes to recognize certain types of cancer.

These techniques can be necessary if the immune system does not recognize the cancer cell antigens as a threat. However, if the body naturally recognizes and attacks a malignant tumor, patients are viable for treatment with tumor-infiltrating lymphocyte therapy.

Tumor-Infiltrating Lymphocytes

The immune system is naturally capable of responding to certain forms of cancer, but it can still be overpowered. A prolonged battle can lead to exhaustion of T lymphocytes. Cancer causes unregulated cell growth, which can easily outpace the production of T cells in the body. One solution to this problem is tumor-infiltrating lymphocyte (TIL) therapy. TIL therapy involves the expansion of a patient’s activated T cell population to bolster their immune response.

Tumor-infiltrating lymphocytes are immune system cells present in some tumors. Their function is to seek out and destroy tumor cells at the source. In TIL therapy, these cells are extracted from a tumor during a biopsy and multiplied. After a substantial number of TILs have accumulated, they are infused back into the patient to actively attack cancer cells while ignoring healthy cells. Chemotherapy is performed in conjunction with TIL therapy to weaken the tumor before infusion.

The first step of this process is to retrieve a sample from the cancerous tumor. Once a sample is obtained, the T cells must be separated from other substances. This can be done using a variety of different cell sorting techniques. Traditionally, researchers have used flow cytometry to purify TILs, this method involves the sortation of cells through a laser based on their physical characteristics (density, size, etc.). While flow cytometry gets the job done, it’s an expensive and time-consuming process. Buoyancy activated cell sorting (BACS) provides a quick and easy alternative for a fraction of the price. This strategy harnesses the buoyant properties of polymer-lipid glass microbubbles to float target cells to the top of a solution for collection.

After isolating activated TILs, they are tested for effectiveness. The cells are co-cultured with mutated DNA from the tumor to examine which TILs can attack the cancer cells if they adapt. These flexible lymphocytes are then multiplied. Scientists use a protein called interleukin-2 (IL-2) to rapidly increase the population of T cells. Once a enough TILs are present, they can be infused back into the patient through an IV.

Treatments

Currently, TIL therapy can be used to treat melanoma, variations of carcinoma, lung cancer, breast cancer, and genitourinary cancer. In each of these tumors the process is the same, but the neoantigens are different. Neoantigens are modified markers on tumor cells that can only be recognized by certain T lymphocytes. Culturing the correct receptors for each neoantigen is a crucial step in TIL therapy. Aside from the matching process, this cell therapy is essentially just utilizing the T cells which already target a patient’s tumor to treat their cancer.

Limitations

Since TIL therapy primarily uses T cells found within the body, the procedure is not as harmful as other adoptive cell therapies. The main drawback is the therapy’s inability to generate more T cells in vitro, or within the body. To combat cancer, TIL therapy must be performed routinely to replenish T lymphocytes and keep their numbers high. This can cost the patient a lot of time and money while also exhausting their immune response. Repeated instances of chemotherapy begin to wear on the body and could lead to increased toxicity.

Chemotherapy is the treatment of diseases with chemical substances. Depending on the disease, the cytotoxins can slow down the spread of or destroy certain pathogens. While this process is necessary in TIL therapy to weaken the body’s defenses before infusion, too much exposure can hinder bodily processes.

The next step in TIL therapy research is finding a way to program the production of activated T lymphocytes without repetitive and invasive procedures. If patients could receive a constant supply of TILs without needing recurring infusions and chemotherapy, cancer treatment would become much more convenient for both parties. Until these advancements are made, the streamlining of TIL therapy falls mainly on the process of cell separation.

Cell Separation

As previously mentioned, cell isolation can require a lot. With more traditional methods like flow cytometry, purification can be a daunting task. The necessary equipment runs at a very high price, and the training required to use and maintain it takes a lot of time. Flow cytometry does successfully sort T cells, but it also absorbs a large amount of resources that could be more beneficial if dedicated toward other aspects of the research and treatment.

BACS is not only quick and easy, it’s also careful with the sample. Methods that use magnets or flowing samples put fragile cells at risk of being damaged. Especially when trying to isolate as many T cells as possible, lost cells can be detrimental to the throughput of a sortation cycle. A combination between microbubbles’ strong but soft structures and the gentle stirring of a sample being the only outside force ensures the safe delivery of target cells.

Akadeum Life Sciences

The low costs and high rewards of microbubble technology make it beneficial to researchers at any level. BACS can isolate T cells faster than other methods without risking damage to the cell population. Whether you work for a huge organization, or are trying to pull together an independent project, Akadeum’s products can help you maximize your potential.

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