Date: 2018-05-03
Type of
information: Treatment of the first patient
phase: 1
Announcement: treatment of the first patient
Company: Celyad (Belgium)
Product: CYAD-01 (CAR-T NKG2D)
Action
mechanism:
- cell therapy/immunotherapy product/gene therapy/CAR-T cell therapy. CYAD-01 (NKG2D CAR T-Cell) is an autologous chimeric antigen receptor T lymphocyte (CAR T-cell) therapy constructed using the native sequence of non-engineered natural killer cell (NK cell) receptors which, unlike traditional CAR technologies such as those targeting the CD19 antigen, have the potential to target a broad range of solid tumors and blood cancers by targeting ligands present on numerous cancer types.
- CAR-T NKR-2 is engineered to express the human NK receptor, NKG2D, which is an activating receptor. It triggers cell killing through the binding of NKG2D to any of eight naturally occurring ligands that are known to be overexpressed on more than 80% of tumors.
- The research underlying this technology was originally conducted at Dartmouth College by Professor Charles Sentman, and has been published in numerous peer-reviewed publications such as Journal of Immunology, Cancer Research and Blood.
- Preclinical results indicate that CAR-T NKR-2 has multiple mechanisms of actions. It inhibits the mechanisms that enable tumors to evade the immune system, activates and recruit anti-tumor immune cells and disrupts the blood supply to the tumor. These mechanisms promote the induction of adaptive immunity, meaning the development of a long-term immune memory against specific tumor antigens of the targeted tumor.
- Celyad is developing both autologous and allogeneic CAR-T NKR-2 approaches. For autologous CAR-T NKR-2, Celyad collects the patient’s own T-Cells and engineers them to express NKG2D in order to target cancer cells effectively.
- Celyad’s allogeneic platform engineers the T-Cells of healthy donors, to also express TCR Inhibitory Molecules (TIMs), to avoid having the donor cells rejected by the patient’s normal tissues.
Disease: colorectal cancer
Therapeutic
area: Cancer - Oncology
Country: Belgium
Trial
details:
- SHRINK (Standard CHemotherapy Regimen and Immunotherapy with NKR-2) is an open-label Phase I study evaluating the safety and clinical activity of multiple doses of CYAD-01, administered concurrently with the neoadjuvant FOLFOX treatment in patients with potentially resectable liver metastases from colorectal cancer.
- The trial contains a dose escalation and an extension stage. The dose escalation design will include three dose levels adjusted to body weight: up to 3x108, 1x109 and 3x109 of CYAD-01. At each dose, the patients will receive three
successive administrations, two weeks apart at the specified dose. The dose escalation part of the study will enroll up to 18 patients while the extension phase would enroll 21 additional
patients. (NCT03310008)
Latest
news:
- • On May 3, 2018, Celyad announced the successful injection of the first patients in the SHRINK trial targeting metastatic colorectal patients. No toxicity observed to date in first patient enrolled in the SHRINK trial (concurrent administration of CYAD-01 with standard chemotherapy)
- • On March 29, 2018, Celyad announced that the company will present updates on its SHRINK clinical trial in metastatic colorectal cancer at the American Association for Cancer Research (AACR) Annual Meeting.
- • On July 20, 2017, Celyad announced the initiation of the SHRINK trial with CYAD-01 (CART NKG2D). The trial is targeting metastatic colorectal patients. SHRINK will be conducted in Belgium in key oncology centers. The colorectal cancer indication evaluated in the SHRINK trial was selected based on evidence generated in the pre-clinical settings and in the ongoing THINK study.
Is
general: Yes
