Cell Medica Earns $8.7 Million Grant to Accelerate Off-the-shelf CAR-NKT Cell Therapy

Aiming to support the development of CMD-502, a new cell-based therapy that uses donor-derived natural killer T-cells to fight cancer, the Cancer Prevention and Research Institute of Texas (CPRIT) has awarded Cell Medica an $8.7 million grant.

In addition to being available “off-the-shelf,” the therapy — being developed in collaboration with the Baylor College of Medicine (BCM) — is expected to have a better safety profile than current chimeric antigen receptor (CAR) T-cell therapies.

Typically, CAR T-cell therapies use a cancer patient’s own immune T-cells, which are modified in the lab to recognize certain cancer proteins and attack any cells producing them. After being expanded to several millions, the cells are reintroduced into the patient’s bloodstream, where they will fight cancer.

But, in addition to having limited effectiveness in solid tumors, these approaches often require a significant amount of time — that patients don’t have — to be manufactured. Also, in some cases, researchers cannot collect enough T-cells to produce the therapy.

Another obstacle of CAR-T-cell therapy is the high rate of potential life-threatening side effects, including severe neurotoxicity and cytokine release syndrome (CRS), which is a systemic immune reaction causing high fever and flu-like symptoms that often are life-threatening.

If CAR T-cells are produced from healthy donors, another complication called graft-versus-host disease (GvHD) may occur, which is a serious complication in which the donor T-cells see the host’s body as a threat and attack it.

“Although existing autologous CAR-T cell therapies have demonstrated impressive response rates, the patient-specific manufacturing process is technically challenging, costly, and time-consuming, and comes with complex logistics and substantial treatment delays. The unique properties of NKT cells bring the potential to solve these challenges,” Carlos Ramos, MD, said in a press release. Ramos is associate professor, Center for Cell and Gene Therapy, at BCM.

Natural killer T (NKT) cells are a subpopulation of T-cells that combine  characteristics of natural killer (NK) and T-cells. A crucial advantage of these compared with conventional T-cells is that they do not induce GvHD and are capable of reaching solid tumors.

CMD-502, Cell Medica’s most advanced CAR NKT-cell therapy, is an off-the-shelf product that targets the CD19 protein, found in most lymphoma and leukemia cells. In addition to the CD19 receptor, CMD-502 cells also are engineered to produce interleukin-15, a signaling molecule that makes these cells last longer and have be more effective against tumors. Researchers are hoping to generate 150 doses of CMD-502 from a single donor.

A Phase 1 clinical trial testing this approach is expected to begin in mid-2019. The ANCHOR study will test escalating doses of CMD-502 in adults with relapsed or refractory diffuse large B cell lymphoma, acute lymphoblastic leukemia, and chronic lymphocytic leukemia.

“It has been a great pleasure working with the multi-disciplinary team at Cell Medica in the development of its versatile CAR-NKT platform. Off-the-shelf CAR-NKT cell therapy has the potential to become a better and simpler approach to CAR therapy for patients with hematological and solid tumors,” said Ramos, who also is ANCHOR’s principal investigator.

In 2012, CPRIT awarded a $15.3 million grant to Cell Medica that allowed the company to settle in Houston, Texas.

“CPRIT was instrumental in enabling us to establish our US operations in Texas, so we are delighted to extend that collaboration through a further grant. This funding will accelerate development of our off-the-shelf CAR-NKT pipeline and, given CPRIT’s deep and broad review, also brings a strong independent validation of our platform and approach,” said Chris Nowers, CEO of Cell Medica.