Cancer Immunotherapy: Tumor-Infiltrating Lymphocytes

Boosting Activated T-Cell Responses

Image from Beth Israel Deaconess Medical Center

Tumor Immune Microenvironment

The tumor microenvironment (TME) consists of a variety of different components, including the cancer cells, blood and lymph vessels supplying the tumor, and of note, tumor infiltrating immune cells and cytokines and chemokines that regulate immune responses. These immune cells make up the tumor immune microenvironment (TIME), and include myeloid-derived suppressor cells (MDSC), tumor-associated macrophages (TAM) and cytotoxic lymphocytes. Studies show that increased MDSC & TAM density in the TME can actually help the tumor grow, while increased numbers of cytotoxic lymphocytes can help fight the tumor and promote recovery.

Image Source: Halozyme Therapeutics

Taking Advantage of Tumor Invading Lymphocytes

Dr. Steven Rosenberg | Image from NIH Medline Plus Magazine

“Intuitively, what better place to find T cells that are reacting against the cancer than in the stroma of the cancer itself?”

— Dr. Steven Rosenberg

From the biopsy, the DNA of tumor cells is analyzed to identify antigens that are mutated (neoantigens) enough such that the immune system can target these antigens without also attacking normal body cells expressing those antigens. From this, the epitopes, which are the specific parts of the neoantigens that can be recognized by the immune system are designed and inserted into dendritic cells also extracted from your body.

Impact of TIL Therapy

So far, TIL therapy has been effective against a few cancers, including melanoma, colorectal cancer, bile duct cancer, and breast cancer. In the case of melanoma, TIL therapy achieved objective response rates (ORR), a measure of the proportion of patients that show a partial or complete response to therapy, of 40–50%, with 10%-20% of patients demonstrating a complete response, often lasting for 3–5 years.

“It’s somewhat ironic that the very mutations that cause a certain cancer may turn out to be its Achilles’ heel and enable immunotherapy treatment.”

— Dr. Steven Rosenberg

However, TIL therapy is yet to be commercialized because the procedure is long and expensive to perform. However, innovations continue to occur, mainly focusing on reducing the time required to produce the T-cells. For example, Iovance Biotherapeutic developed a new process that takes just 16 days to produce the T-cells.

18 y/o innovator working on reversing ageing and researching cancer vaccines. www.akshajdarbar.com