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 keeping with analysis revealed in Medical Most cancers Analysis.

“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 writer of the research. “Dendritic cell vaccines have the potential to harness the sufferers’ personal immune system to get them into remission and probably preserve the most cancers from coming again.”

ASCT is often preceded by induction remedy with chemotherapy to kill as many most cancers cells as potential and induce a remission. For this research, the investigators chosen sufferers with high-risk illness who nonetheless had lively myeloma after induction remedy and earlier than receiving ASCT, which constitutes a damaging prognostic issue. “We centered 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 international 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 specific survivin and induce an immune response towards the protein.

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

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 acquired 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 probability of triggering a survivin-specific response, Locke and staff engineered the dendritic cells to specific a model of the complete protein, with a mutation to extend security with out compromising immunogenicity.

The vaccine together with ASCT was properly tolerated, with solely minor hostile 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 had 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 had 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 knowledge suggesting the four-year progression-free survival of this affected person inhabitants to be roughly 50%,” stated Locke.

“Our research confirmed that we will goal survivin with a vaccine-based strategy and induce immune responses, and it urged that this technique might in the end assist enhance affected person outcomes,” added Locke. “Bigger, randomized research are wanted to substantiate our findings and to evaluate whether or not transferring vaccination to earlier within the illness course could be helpful in stopping sufferers from creating aggressive types of myeloma.”

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

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