Our Focus

Cancer Immunotherapy

a potentially transformative approach to treating cancer

Our initial focus in cancer immunotherapy is on delivering sustainable and effective T cell therapies to patients with cancer. We are leveraging our core expertise in gene transfer technology and our experience in implementing gene therapy clinical trials to build a broad, fully integrated immuno-oncology franchise.

For years, the standard of care for treating cancer was surgery, chemotherapy and radiation. For a variety of cancers, cancer immunotherapy, based on CAR T cells presents a promising new treatment option.

Our cancer immunotherapy research group is focused on the next generation of T cell engineering and creating a pipeline of T cell product candidates to treat a wide variety of liquid and solid tumor cancers.

CAR T program

leveraging our gene therapy expertise to treat cancer

Our gene therapy technology can genetically modify a patient’s own T cells to target and destroy cancer cells. In advanced clinical studies, academic researchers have shown that modified T cells, called chimeric antigen receptor, or CAR T cells, can provide a potentially curative option for patients with a variety of lymphomas (blood tumors), after other treatment approaches have failed.

Like our programs for hematopoietic stem cells (stem cells from the patient) in rare genetic disorders, our CAR T technology uses a customized lentiviral vector to alter T cells so the T cells can recognize specific proteins on the surface of cancer cells or other diseased cells and kill them.

With our CAR T technology, we harvest a patient’s white blood cells (a process called leukapheresis) and activate certain T cells to grow. The gene sequences for the CAR construct are transferred into the T cell DNA using a lentiviral vector. T cells are then grown to numbers sufficient for the desired patient dose. These genetically engineered cells, which will express the receptors that can recognize the exact proteins that are characteristic of specific cancers, are then infused back into the patient. The genetically engineered CAR T cells are designed to supplement a patient’s immune system and can be further engineered to overcome immune evasion mechanisms used by cancer cells.

our immunotherapy focus

We currently have active clinical and pre-clinical research programs targeting multiple different, novel oncology antigens, including B-cell maturation antigen (BCMA) and the human papillomavirus type 16 E6 (HPV-16 E6) oncoprotein. These programs include various T cell therapies with significant academic and industry collaborations.

Our lead CAR T program, bb2121, in collaboration with Celgene, is being evaluated in a Phase 1 clinical study, CRB-401, for the treatment of relapsed/refractory multiple myeloma. In February 2016, we announced the first patient treated in the study. At the 57th American Society of Hematology Annual Meeting in December 2015, we announced the first pre-clinical data from our anti-BCMA program, including for bb2121, in three poster presentations, covering critical basic research, translational and manufacturing aspects of our T cell oncology pipeline.

We presented the first, interim data for bb2121 at the 28th EORTC-NCI-AACR Molecular Targets and Cancer Therapeutics Symposium in December 2016.

leveraging the best science through strategic partnerships

immune system and T cells

We believe the use of human cells as therapeutic entities to re-energize the immune system will be the next significant advancement in the treatment of cancer. These cellular therapies are designed to avoid the long-term side effects associated with current treatments and have the potential to be effective regardless of the previous treatments patients have experienced. Our CAR T cell technology, based on our lentiviral vector technology and experience, is designed with the intent to deliver a payload of potent T cells that can kill cancer cells, specifically and directly.

The immune system recognizes danger signals and responds to threats at a cellular level. It is often described as having two arms. The first is the innate immune system, which recognizes non-specific signals of infection or abnormalities as a first line of defense and creates the initial response. The response is the same every time regardless of prior exposure to the infectious agent. The second arm is the adaptive immune system, composed of highly specific, targeted cells. It provides long-term recognition and protection from infectious agents and abnormal processes such as cancer. The adaptive immune response can be humoral, antibody-based, or cellular, which includes T cell-based immune responses.

The most significant cellular components of the adaptive immune response are T cells, so called because they typically mature in the thymus. T cells are involved in sensing and killing infected or abnormal cells, as well as coordinating the activation of other cells in an immune response. These cells are classified into two major subsets: CD4+ T cells and CD8+ T cells, based on cell surface expression of the CD4 or CD8 glycoproteins. Both subsets of T cells have specific functions in mounting an immune response to clear an infection or eliminate cancerous cells. CD4+ T cells, or helper T cells, are involved in coordinating the immune response by enhancing the activation, expansion, migration, and effector functions of other types of immune cells. CD8+ T cells, or cytotoxic T cells, can directly attack and kill cells they recognize as infected or otherwise abnormal, and are aided by CD4+ T cells. Both types of T cells are activated when their T cell receptor recognizes and binds to a specific protein structure on the surface of another cell. This protein structure is composed of the major histocompatibility complex, or MHC, and a small protein fragment, or peptide, derived from proteins inside the cell or on the cell surface. Circulating CD4+ and CD8+ T cells survey the body, differentiating between MHC/peptide structures containing “foreign” peptides and those containing “self” peptides. A foreign peptide may signal the presence of an immune threat, such as an infection or cancer, causing the T cell to activate, recruit other immune cells, and eliminate the targeted cell.

Although the immune system is designed to identify foreign or abnormal proteins expressed on tumor cells, this process is either ineffective or defective in cancer patients. The defective process sometimes occurs when cancer cells closely resemble healthy cells and go unnoticed or if tumors lose their MHC protein expression. Additionally, cancer cells employ a number of mechanisms to escape immune detection to suppress the effect of the immune response. Some tumors also encourage the production of regulatory T cells that block cytotoxic T cells that would normally attack the cancer.