A triple combination treatment — dendritic cell vaccination plus Revlimid (lenalidomide) and an anti-PD-1 checkpoint inhibitor — led to stronger anti-tumor immune responses against myeloma in mice, a study reports.
Multiple myeloma is a type of blood cancer characterized by the infiltration of malignant plasma cells into the bone marrow. Despite current therapies, anticancer and stem cell transplant, most patients relapse because tumor cells manage to evade being targeted and killed by immune cells.
Treatment failures prompted researchers to look for approaches that would be able to bypass the lack of immune surveillance.
They may have found one such therapy: the combination of a dendritic cell vaccination with Revlimid and anti-PD-1 checkpoint blockade immunotherapies.
Dendritic cells (DCs) are the strongest type of antigen-presenting cells (APCs) — cells that tell T-cells what their targets are. In this way, DCs play a key role in inducing and maintaining anti-tumor immune system responses.
While immune cells from myeloma patients are often less active, contributes to immune tolerance of myeloma cells, studies have shown that the function of DCs can be restored and boosted.
This is achieved through specific techniques applied to cells taken from patients and grown in the lab. Once these cells are modified, they can then be injected back into patients to exert their immune function, a process called DC vaccination.
Revlimid is an immunomodulatory agent that detects tumor cells when the immune system is suppressed, while anti-PD-1 immunotherapies — like Opdivo, Keytruda, or Tecentriq — block the activity of the PD-1 receptor to prevent cancer cells from evading T-cells.
To investigate if the therapeutic efficacy of a DC vaccine could be enhanced in combination with Revlimid and anti-PD-1, investigators tested different combinations in animals models of multiple myeloma.
Animals were divided into five distinct groups: control animals, those that received DCs alone, those given DCs with either Revlimid or anti-PD-1, and finally those that received all three therapies combined.
The combination of DC vaccination plus Revlimid and anti-PD-1 blocked tumor growth more effectively compared to the other groups. This effect was accompanied by a significant reduction in the number of immunosuppressive cells and an increase in immune effector cells.
Data also showed the activity of T-cells and natural killer (NK) cells was enhanced in animals given the triple combination, while the levels of immunosuppressive cytokines – molecules that mediate and regulate immune and inflammatory response – was significantly reduced.
These findings indicate that the triple combination of DC vaccination plus Revlimid and anti-PD-1 leads to a robust anti-tumor immune response against myeloma by two distinct mechanisms.
First, it blocks the activity of immunosuppressive cells that could hamper the body’s immune response against the tumor. Second, it promotes the activation of immune cells that are able to detect and kill tumor cells.
“We hereby propose a framework for a more efficacious DC-based vaccination strategy against [multiple myeloma] with the combination of immunomodulatory drug lenalidomide and anti-PD-1 antibody,” the investigators wrote.