Immunotherapy cascade drug inducers of the immune response

Researchers have launched a study of an immunotherapy drug that may add a new tool to the immune system’s arsenal against cancer. The immune system needs extra help, because it doesn’t always recognize cancer as a threat, and sees cells as the body’s own, not the harmful mutations they have become. So when cancer cells pass through protein molecules called “checkpoints,” which are so called because they “monitor” cells to gauge their risks to the body’s health, the cancer cells send out deceptive signals that mimic the normal cells they used to be, allowing them to pass undetected. .

A promising class of immunotherapy drugs known as checkpoint inhibitors work by disrupting those signals, exposing cancer cells to the immune system and launching a potential attack. Immunotherapy drugs now on the market target three checkpoint receptors: PD-1, PD-L1 and CLTA-4. These checkpoint inhibitors are currently approved for advanced melanoma, non-small cell lung cancer, renal cell carcinoma, Hodgkin lymphoma, bladder cancer, and/or squamous cell carcinoma of the head and neck.

Explore new options

A new Phase 1 trial studies a drug, currently called TSR-022, that is trying to block another checkpoint that has not yet been a target for an approved drug: TIM-3. “We hope to achieve many things,” says Dr. Glenn Weiss, director of clinical research and phase I and II clinical trials at our hospital near Phoenix and the study’s principal investigator. “We want to be able to investigate new treatment options for our patients with advanced cancers, determine how safe a drug is and how it should be dosed, and see if it leads to long-term results.”

What may distinguish TSR-022 from approved checkpoint inhibitors is the potential cascading effect it can produce if it elicits an immune response. According to a 2014 article published by the American Association for Cancer Research (AACR), TIM-3 receptors are not only found in T cells in tumors, but are also linked to the presence of other cells that can cause a short circuit in tumors. immune system. and/or promote tumor growth. Therefore, targeting TIM-3 can not only reactivate T cells but also lead to the establishment of other cellular interactions beyond the design of current immunotherapy drugs. For example:

• Scientists believe that TIM-3 may attract regulatory T cells (Tregs) that crowd around the tumor microenvironment and suppress the immune system. Tregs are necessary for the immune system to prevent the T cells from being disturbed.
• Some research suggests that TIM-3 may enhance the presence of myeloid-derived suppressor cells. These cells help regulate the immune system, but they may also be responsible for the poor response to cancer treatments.
• TIM-3 is found in dendritic cells, and may prevent them from initiating an immune response. Dendritic cells are like the immune system’s traffic police, sending T cells in the right direction to attack invaders.

How do PD-1 inhibitors work?

PD-1 checkpoint inhibitors are designed to work in a cause-and-effect manner. It blocks the communication between the cancer cell and the immune cell at the PD-1 checkpoint, which leads to an attack on the cancer cells. Dr. says. Vice’s TSR-022 is “designed to have a broader impact.” It blocks TIM-3, and the potential interaction can resemble a line of cellular dominoes falling off one by one, opening cancer cells to multiple attacks.

The AACR article says that TIM-3 is present in patients with melanoma, non-small cell lung cancer, and non-Hodgkin’s lymphoma, but this trial includes adult patients with solid tumors who meet other specific requirements regarding previous anticancer therapies. The trial studies how TSR-022 works alone and in combination with a PD-1 inhibitor. Our hospital near Phoenix was the first site in the world to administer TSR-022 as part of a phase I clinical trial. TSR-022 was developed by TESARO Inc. in Waltham, Massachusetts, in association with AnaptysBio Inc. in San Diego.

Learn more about the science behind immunotherapy.