SLAMF7 regulators are therapeutics that can modulate the activity of SLAMF7 (signaling lymphocytic activation molecule F7), a receptor abundantly found on the surface of myeloma cells.

An example of a SLAMF7 regulator is Empliciti (elotuzumab), a humanized antibody against SLAMF7, developed and marketed by Bristol-Myers Squibb. Empliciti was approved by the U.S. Food and Drug Administration (FDA) to treat relapsed or refractory myeloma in combination with immunomodulatory agents, Revlimid (lenalidomide) or Pomalyst (pomalidomide), and the steroid dexamethasone.

SLAMF7 and multiple myeloma

SLAM F7 is abundantly found on the surface of myeloma cells but not on normal cells or stem cells. A soluble form of SLAMF7, called sSLAMF7, is also located in the plasma (the liquid portion of the blood) of myeloma patients, but not in the plasma of healthy donors.

In addition, SLAM F7 is found at lower levels on the surface of several types of immune cells such as natural killer (NK) cells, CD8+ T-cells, activated monocytes, and dendritic cells.

It is a co-stimulatory receptor molecule involved in the regulation of the immune response. This means that it can activate or dampen the immune response when two different subsets of immune cells interact with each other. For example, its high production by myeloma cells acts to suppress the immune response so that the malignant myeloma cells can grow and thrive.

How SLAMF7 regulators work

SLAMF7 regulators bind to SLAMF7 found on the surface of myeloma cells as well as to the CD16 receptor found on NK cells, thereby activating NK cells. The activated NK cells release toxic proteins into the myeloma cells and induce cell death. This process is called antibody-dependent cellular cytotoxicity.

These regulators can also directly bind to SLAMF7 found on NK cells and enhance their ability to kill SLAMF7-positive myeloma cells.

Finally, the binding of these regulators to myeloma cells disrupts their adhesion to the bone marrow cells, thereby promoting their sensitivity to NK cell-mediated killing.

Novel SLAMF7 regulators

A study published in the journal Blood showed the potential of SLAMF7 chimeric antigenic receptor T-cells (SLAMF7-CAR T-cells) in treating myeloma. In vitro experiments showed that SLAMF7-CAR T-cells efficiently killed primary myeloma cells isolated from new and relapsed or refractory myeloma patients. In vivo experiments using a murine xenograft model showed that myeloma could be treated with a single administration of SLAMF7-CAR T-cells.

A Phase 1 clinical trial (NCT03958656) is currently recruiting an estimated 42 participants in the U.S. to investigate the safety and efficacy of SLAMF7-CAR T-cells in treating myeloma. The trial is expected to be completed in May 2024.

 

Last updated: Feb. 6, 2020

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