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Tumors are masters of deception. Cancer cells destroy healthy tissue, but they hide their activities and escape the natural defenses of the human body. The immune system does not see through deceit.
Novartis drug researchers and oncology researchers around the world are finding ways to thwart tumors. The new cancer immunotherapies are achieving substantial success for many patients, but it is possible to expand their reach.
Novartis scientists are studying several approaches to increase the immune response to cancer, including immune cell education, activation, and tumor priming for an immune response. In addition, they are exploring the possibility of combining immunotherapies by looking for clues in a tumor that could help them match the right immunotherapy to the right patient.
Immune education
Some cells of the immune system are students for life. They can be taught to attack unwanted invaders, including cancer cells. An approach adopted by Novartis scientists in immune education involves the use of chimeric antigen receptor (T-CARD) T cells. This approach drives the patient's own immune cells – special cells called T cells that act as immune system soldiers – to identify and attack cancer cells. The training involves giving the T cells the necessary instructions to create a sensor that detects an enemy flag on the cancer cells. Here, CAR-T cells (green sensors) recognized a cancer cell (red) and launched an attack.
Immune activation
As a crook, cancer knows how to trick the immune system into believing that there are no sick cells to attack. The signals used by a tumor to play its tricks are a normal part of the immune system. They can alter immune behavior in many ways, for example by masking tumor cells or by disabling immune cells. Novartis researchers are exploring various methods to eliminate these deceptive molecular signals and activate the immune cells of the tumor. For example, a tumor-driven signal is called a checkpoint, a set of brakes that normally prevents immune cells from damaging healthy cells. Tumors exploit control point signals to prevent ghost cells in the immune system from attacking cancer cells. Here, a checkpoint inhibitor lifted the brakes and activated the T cells (blue) to attack and destroy a cancer cell (pink).
Microenvironment prepared
Beautiful, is not it? Appearances can be deceiving. This is a tumor. Much more is happening than the growth of cancer cells. The researchers recognize that the parts of a tumor surrounding cancer cells, the tumor microenvironment, may be as important to consider as the cancer cells themselves. Novartis scientists are looking for ways to improve the microenvironment of the tumor to make immunotherapy more effective.
Matchmaking of immunotherapy
Why do some patients respond to therapy while others, apparently similar, do not? It's a mystery, but Novartis scientists believe that an answer could lie in the details of the tumor itself. For example, the distribution and abundance of immune cells in a tumor might give clues to the efficacy of a patient in immunotherapy. To explore this possibility, Novartis scientists turned to artificial intelligence (AI) to see if computer programs could find clues in slide images of cancer pathology. As a first step, Novartis pathologists are working with the technology start-up PathAI to form an AI platform for recognizing cell types on pathology slides. Here, IA has identified tumor cells (red), immune cells (green, yellow) and other cells (black, purple).
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