MD Anderson Novel Cell-based Immunotherapy Produces Results for CLL & NHL Patients

MD Anderson Novel Cell-based Immunotherapy Produces Results for CLL & NHL Patients

MD Anderson Cancer Center led a new cell-based immunotherapy clinical trial demonstrated powerfully positive results for 11 patients with either chronic lymphocytic leukemia (CLL) or non-Hodgkin’s lymphoma (NHL) who had exhausted all other treatment options.

The Study

Led by MD Anderson Cancer Center, this study involves a type of immune cell called a Natural Killer (NK) cell. For this study the NK cells were engineered to target a protein called CD19 found on B-lymphoblasts and which can become cancerous and trigger a number of blood cancers. The study teams sought to learn if giving genetically changed immune cells, called CAR-NK cells, after chemotherapy will improve the disease in stem cell transplant patients with relapsed (has returned) and/or refractory (has not responded to treatment) B-cell lymphoma or leukemia. Additionally, researchers will seek to identify the highest tolerable dose of CAR-NK cells to give to patients with relapsed or refractory B-cell lymphoma or leukemia as well as assess the safety of this approach.

The investigational Phase I/2 study involves the making of and infusion of genetically changed NK cells and the drug AP1903 (originally Bellicum Pharmaceuticals)—both of which are not FDA approved or commercially available for use in this type of disease. The chemotherapy used in this study included fludarabine, cyclophosphamide and mesna and are commercially available and FDA approved.

In total, up to 36 patients will participate in this study all at MD Anderson in Houston, Texas.


The MD Anderson-based team reported that the administration of CAR-NK cells was not associated with the development of cytokine release syndrome, graft-versus-host disease and there was no increase in levels of inflammatory cytokines, such as interleukin-6 over baseline. They reported that the maxim tolerated dose was not achieved. Out of 11 patients who were treated, 73% had a response and of this subgroup 7 (4 with lymphoma and 3 with CLL) had a complete remission, and 1 had remission of the Richter’s transformation component but had persistent CLL.  

Of note, the responses were rapid—seen within 30 days after infusion—at all dose levels. Moreover, the CAR-NK cells expanded and persisted at low levels for at least 12 months.

The investigators concluded that among the 11 patients with relapsed or refractory CD19-positive cancers, a majority had a response to treatment with CAR-NK cells without the development of major toxic effects.

Takeda & MAD Anderson Deal

MD Anderson has licensed its CAR NK platform and the exclusive rights to develop and commercialize up to four programs, including CD19-targeted CAR NK-cell therapy and a B-cell maturation antigen (BCMA)-targeted CAR NK-cell therapy. The duo will also collaborate to develop the CAR NK programs. Takeda is responsible for the development, manufacture and commercialization of CAR NK products resulting under the agreement. Takeda will pay MD Anderson an upfront payment (didn’t disclose amount) and they will be eligible to receive development and commercial milestones for each of the four targets as well as tiered royalties on net sales of any such CAR NK product.

Principal Investigator Comments

Kathy Rezvani, MD, PhD, who led the Phase I/2 study, commented on the Takeda collaboration, saying, “Our vision is to improve upon existing treatments by developing armored CAR NKs that could be administered off-the-shelf in an outpatient setting—enabling more patients to be treated effectively, quickly and with minimal toxicities.” Rezvani continued, “With their expertise in hematologic malignancies and commitment to developing next-generation cell therapies, Takeda is the ideal collaborator to help our team advance CAR NK-cell therapies to patients in need of treatments.”

Takeda Responsibility

Takeda seeks to investigate multiple approaches to improve the safety, efficacy and accessibility of first-generation CAR T-cell therapies. They have established CD19 CAR NK as their lead cell therapy candidate in oncology reports Andy Plump, MD, PhD, President of Research and Development. In addition to CAR NK-cell therapies, Takeda and its partners are investigating multiple approaches, including gamma delta CAR Tsinduced pluripotent stem cell-derived CAR Ts, CAR Ts targeting solid tumors, and other next-generation approaches

Lead Research/Investigator

Katy Rezvani