Center for Cellular Immunotherapy

Center for Cellular Immunotherapy

Recent introduction of pioneering cellular immunotherapies, capable of eliciting highly effective anti-tumor immune responses, has set the stage for a new era in personalized medicine for cancer patients. The Rambam Center for Cellular Immunotherapy is dedicated to advance cellular therapies that employ key players of the immune system, such as T cells and natural killer (NK) cells, and modify them using emerging innovative technologies.

These unique therapies are designed to treat hematological and solid malignancies as well as autoimmune diseases. The major goals of this center are to improve therapeutic responses, expand indications for additional diseases and reduce the duration of chimeric antigen receptor (CAR)-T cell manufacturing.

The Applied Medical Technology Research Center (MATRiC) operates as a ‘focal knowledge hub’ in the field of regenerative medicine, from the cellular to the tissue level, with a focus on developing clinically relevant structured human tissues for transplantation, drug screening, and precision medicine.

The Center's professional team collaborates with researchers from Rambam, academia and leading industries to answer clinically unmet needs across the hospital's departments. Leveraging advanced technologies in the fields of stem cells, tissue engineering, 3D bioprinting, and organ-on-chip devices.


Center for Cellular Immunotherapy

Who we are

The Center is headed by Dr. Ofrat Beyar-Katz, MD, PhD, a hematologist specialized in CAR-T cell therapy. She did her post-doctoral fellowship at one of the most advanced centers for cellular therapy, the University of Pennsylvania (UPenn). The lab manager is Dr. Noga Setter Marco leading a multidisciplinary team, including PhD researchers and support staff specially trained in the field to ensures the comprehensive approach required to achieve the established goals.

What do we do?

CAR-T cells: To acquire the ability to kill tumor cells T-cells need to undergo the process of "re-education" through genetic engineering performed at a specialized lab. Ultimately, T-cells are modified to express a CAR. To date, several CAR-T cell products have been approved for the treatment of certain hematological malignancies.  CAR-T cell agents are provided on a regular basis, as they are included in the national “drug basket” and health insurance package in Israel. However, while these promising therapies have shown to be highly effective in additional hematological malignancies, they have not yet been approved for these indications. Patient outcomes may be further improved by novel genetic modifications of the products. To this end, w e at the teamre focusing on the following key issues. First, developing innovative CAR-T cell drugs capable of detecting two antigens, instead of one, on the tumor cell surface.  Second, boosting CAR-T cell activity through enhancing the expression and secretion of various T-cell cytokines. Finally, applying the gene-editing CRISPR technique for insertion, deletion or replacement of specific genes..

Another outstanding issue to be addressed is the long manufacturing time of the products (about 3-5 weeks), which is crucial, given that the clinical condition of some patients can rapidly deteriorate during that period. Once a novel product is designed, it is translated into a clinical product using the self-manufacturing infrastructure of CAR-T cells operating at Rambam under GMP (good manufacturing practice) standards.  These therapies will be administered within the framework of Phase I and II studies.

Tumor infiltrating lymphocytes (TILs): This type of cellular therapy is based on isolation and expansion of T-cells derived from the tumor tissue itself. This modality is used more specifically in the setting of solid tumors.  Following the expansion stage, TILs are injected back to the patient. We are actively collaborating with pharmaceutical companies to ensure the provision of this therapy to cancer patients.

Future plans:

T cell receptor (TCR) cells: Similar to CAR-T cells, the TCR cell therapy involves genetic modification of patient T-cells, making them capable to recognize and attack tumor cells. T-cells are transduced with a construct encoding the alpha and beta chain of a known, high affinity T cell receptor against a target antigen. TCR cells have several key elements that differ them from CAR-T cells, including the ability to target intracellular antigens. They are more frequently used in the setting of solid tumors.
Natural killer (NK) cells: These cells are part of the immune cell repertoire and are crucial for the identification and fighting cancer cells. NK cells are drawn from normal donors and expanded in the laboratory setting. One of the main advantages of this therapy is the low risk of graft-versus-host disease, as compared to other types of cellular immunotherapy. We are currently creating an off-the-shelf NK-based product to be administered alone or in combination with CAR-T cells.

 Meet the Cellular Immunotherapy Center Team

 About Dr. Ofrat Beyar-Katz