How NY-ESO TSR works
Immunotherapies act to improve the body’s ability to fight cancer by boosting the immune system. NY-ESO TCR consists of the patient’s own immune cells, called T-cells, that are modified to enhance their ability to recognize tumor cells. The treatment is developed using Adaptimmune’s SPEAR T-cell technology.
T-cells have a protein on their surface called the T-cell receptor (TCR). When TCR interacts with particular antigens or proteins not normally found in the body, the T-cell recognizes the cell producing the antigen as abnormal and targets it for death.
Adaptimmune has identified the peptide (part of a protein) called NY-ESO-1 that is highly produced by many cancer types but produced only at low levels by healthy cells. Redirecting T-cells to recognize and target NY-ESO-1 should result in a decrease in tumor cell numbers.
To produce NY-ESO TCR, the patient’s own T-cells are isolated from the blood using a process called leukapheresis. Blood is removed from the patient and filtered to collect the T-cells, with the remaining blood being returned to the body. The collected T-cells are genetically modified in the laboratory to produce a specific TCR that is designed to recognize NY-ESO-1 as a target. The modified T-cells are then returned to the patient’s body through an infusion into the bloodstream. It is hoped that these T-cells will multiply in the body and attack cancer cells in a targeted manner, resulting in a decrease in tumor size and spread.
Some patients may receive chemotherapy with cyclophosphamide and/or fludarabine prior to receiving NY-ESO TCR to reduce the number of non-modified immune cells and increase the chance of success of the re-introduced modified T-cells.
NY-ESO TSR in clinical trials
Adaptimmune is currently investigating NY-ESO TCR in five ongoing clinical trials in different types of cancer. These trials aim to assess the long-term safety of the treatment and gain a preliminary evaluation of its anti-tumor activity.
An open-label Phase 1/2 trial (NCT01352286) investigating NY-ESO TCR in 26 patients with advanced multiple myeloma has completed enrollment. The trial is taking place at two sites in the U.S, the Greenebaum Cancer Center at the University of Maryland and the Abramson Cancer Center at the University of Pennsylvania. Preliminary results published in the journal Nature Medicine in 2015 showed that of 20 assessed patients, 16 (80%) had a clinical response to treatment with NY-ESO TCR, with a median progression-free survival of 19.1 months. At the 2016 American Society of Clinical Oncology (ASCO) annual meeting, Adaptimmune provided an update from the trial’s 100th day, showing that 91% of multiple myeloma patients (20 out of 22) had responded to the treatment.
Three additional open-label Phase 1/2 studies investigating NY-ESO TCR are still enrolling patients at multiple sites in the U.S.
An estimated 65 patients with synovial sarcoma are being recruited for an ongoing Phase 1/2 trial (NCT01343043) to receive NY-ESO TCR following chemotherapy. At the 2016 ASCO meeting, Adaptimmune reported that NY-ESO TCR had a 50% response rate in the 12 patients examined so far.
The final Phase 1/2 trial (NCT02588612), assessing NY-ESO TCR treatment following chemotherapy in non-small cell lung cancer (NSCLC) is also enrolling up to 10 patients.
Cytokine release syndrome (CRS) is a common side effect in many T-cell therapies. As of Jan. 27, 2016, Adaptimmune reported that eight of 53 treated patients had experienced CRS. However, the company said the cases of CRS were of manageable severity and have been carefully managed in all patients.
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