Cytovia, Inserm Partnering on NK-based Immunotherapies for Myeloma

A recent collaboration between Cytovia Therapeutics and Inserm, the French National Institute of Health and Medical Research, aims to advance new immunotherapies against multiple myeloma based on natural killer cells.

Cytovia is developing two distinct therapies for myeloma; one activates and brings these immune cells closer to the cancer cells, the other uses engineered natural killer cells that have a greater ability to fight off cancer.

Under the agreement, Cytovia will be able to use specific antibodies developed and patented by Inserm in these treatment approaches. The antibodies target the CD38 protein, which is widely produced by myeloma cells.

The collaboration also includes evaluating these candidates at an Inserm center, the Hôpital Saint-Louis’ Research Institute, under the leadership of Armand Bensussan, PhD, and Jean-Christophe Bories, PhD. Clinical trials are expected in 2022, the company’s website says.

“We are delighted to partner with one of the top centers of excellence in the world for research and treatment in hematology [blood diseases],” Daniel Teper, chairman and CEO of Cytovia, said in a press release. “CD38 is a validated target and natural killer cells have significant cytotoxicity to myeloma cells. We are looking forward to bringing promising new options to address the unmet needs of patients with Multiple Myeloma and aim for a cure.”

Natural killer cells, or NK cells, are an integral component of the human immune system and play a major role in protecting against cancer.

Cytovia has been developing bispecific antibodies that, as their name suggests, bind to two specific targets simultaneously. The company designed its therapies to bind one protein in cancer cells and another in immune cells, tethering these two cell types and unleashing stronger anti-tumor responses.

Cytovia’s candidate for multiple myeloma, CYT-338, binds the NK-activating receptor NKp46 and CD38. In addition to bringing the immune cells closer to the cancer cells, the binding of this therapy to NKp46 is also expected to activate the NK cells.

Moreover, it may induce responses in patients who fail immunotherapies targeting the CD38 protein alone.

“We have demonstrated the selectivity of our novel CD38 antibody in killing myeloma cells but not normal cells such as NK, T, and B cells. The activation of NK cells through NKp46 may enhance the efficacy of the bispecific antibody in patients not responsive to CD38 monoclonal antibody therapy,” said Bensussan, director of the Immuno-Oncology Research Institute at Hôpital Saint-Louis, Paris.

Cytovia is also developing CAR NK cell therapies, which are essentially immunotherapies in which NK cells are engineered to produce a man-made chimeric antigen receptor, or CAR, that helps them recognize and kill cells containing a specific cancer protein.

Under the licensing agreement, Cytovia will be able to use a specific CAR developed at Inserm to create a CAR NK cell therapy, called CYT-538, that targets myeloma cells.

Notably, since CAR NK cell therapies have several safety advantages over more traditional CAR T-cell therapies, including the absence of graft-versus-host disease — a potentially fatal reaction in which the donor immune cells attack and damage the patient’s tissues — they can be developed as “off-the-shelf” products.

Cytovia creates its CAR NK therapies from induced pluripotent stem cells. These are cells derived from either skin or blood cells that were reprogrammed back into a stem cell-like state, allowing for the development of an unlimited source of almost any type of human cell, including NK cells.

“CD38 CAR NK is a promising approach for relapsed/refractory patients and an alternative to CAR T therapies,” Bensussan said.

The licensing agreement was signed between Cytovia and Inserm Transfert, the private subsidiary of Inserm.