Clinical trial finds dendritic cell vaccine safe, induced immune responses in patients with multiple myeloma

A dendritic cell vaccine administered earlier than and after autologous stem cell transplant (ASCT) was secure and immunogenic and was related to sturdy scientific responses in sufferers with high-risk a number of myeloma, in accordance with analysis printed in Clinical Cancer Research.

“A number of myeloma is a continual and incurable most cancers,” stated Frederick L. Locke, MD, chair of the Blood and Marrow Transplant and Mobile Immunotherapy Division at Moffitt Most cancers Middle and senior creator of the examine. “Dendritic cell vaccines have the potential to harness the patients‘ personal immune system to get them into remission and doubtlessly maintain the most cancers from coming again.”

ASCT is often preceded by induction remedy with chemotherapy to kill as many cancer cells as doable and induce a remission. For this examine, the investigators chosen sufferers with high-risk illness who nonetheless had energetic myeloma after induction remedy and earlier than receiving ASCT, which constitutes a detrimental prognostic issue. “We targeted on this affected person inhabitants as a result of they’re most in want of the vaccine,” stated Locke.

Dendritic cells are a vital part of the immune system. They take up overseas proteins, break them down, and current the fragments (peptides) to different immune cells to stimulate an immune response, Locke defined. To provide the vaccine, the researchers engineered the sufferers’ personal dendritic cells to precise survivin and induce an immune response towards the protein.

“Excessive expression of survivin at prognosis is related to poor outcomes,” stated Locke. “Due to this fact, we hypothesized that by focusing on this protein, we may induce an immune response in sufferers who’ve essentially the most aggressive illness and doubtlessly maintain them in remission for an extended time frame.”

Locke and colleagues designed a dendritic cell vaccine focusing on a protein known as survivin and examined this vaccine in a section I scientific trial involving 13 sufferers with a number of myeloma. Sufferers obtained one dose of the vaccine inside 30 days earlier than standard-of-care ASCT and one other dose roughly 21 days post-transplant.

To extend the variety of survivin peptides offered to the immune system, and subsequently the chance of triggering a survivin-specific response, Locke and group engineered the dendritic cells to precise a model of the whole protein, with a mutation to extend security with out compromising immunogenicity.

The vaccine together with ASCT was effectively tolerated, with solely minor antagonistic results noticed. Moreover, the vaccine induced survivin-specific immune responses. Particularly, circulating survivin-specific CD4 T cells and CD8 T cells considerably elevated in roughly 35% and 30% of sufferers, respectively.

Antibodies towards survivin peptides have been detected in two out of 13 sufferers at baseline and 9 out of 13 sufferers after vaccination and ASCT. “General, 85% of sufferers had both a T-cell response or an antibody response towards survivin,” stated Locke.

Seven sufferers skilled an improved scientific response at 90 days post-transplant, all of whom confirmed survivin-specific immune responses. After a median follow-up of 4.2 years, six out of those seven sufferers have been alive and remained disease-free after remedy. The estimated four-year progression-free survival was 71%.

“These outcomes in contrast very favorably to historic information suggesting the four-year progression-free survival of this affected person inhabitants to be roughly 50%,” stated Locke.

“Our examine confirmed that we will goal survivin with a vaccine-based method and induce immune responses, and it instructed that this technique may finally assist enhance affected person outcomes,” added Locke. “Bigger, randomized research are wanted to verify our findings and to evaluate whether or not shifting vaccination to earlier within the illness course can be useful in stopping sufferers from growing aggressive types of myeloma.”

The affected person inhabitants on this examine just isn’t usually included prospectively in scientific trials. Moreover, the remedy panorama for myeloma is quickly evolving, with new-generation therapies reminiscent of CAR T-cell remedy and bispecific antibodies being examined earlier than transplant. Due to these elements, there are limitations to straight evaluating the outcomes from this examine to historic information, Locke defined.

As well as, restricted pattern availability didn’t enable the researchers to verify that the noticed vaccine-specific immune responses have been directed towards the sufferers’ personal myeloma cells.