The tumor-associated antigen RHAMM (HMMR/CD168) is expressed by monocyte-derived dendritic cells and presented to T cells

We formerly demonstrated that vaccination with Wilms' tumor 1 (WT1)-loaded autologous monocyte-derived dendritic cells (mo-DCs) can be a well-tolerated effective treatment in acute myeloid leukemia (AML) patients. Here, we investigated whether we could introduce the receptor for hyaluronic acid-mediated motility (RHAMM/HMMR/CD168), another clinically relevant tumor-associated antigen, into these mo-DCs through mRNA electroporation and elicit RHAMM-specific immune responses. While RHAMM mRNA electroporation significantly increased RHAMM protein expression by mo-DCs, our data indicate that classical mo-DCs already express and present RHAMM at sufficient levels to activate RHAMM-specific T cells, regardless of electroporation. Moreover, we found that RHAMM-specific T cells are present at vaccination sites in AML patients. Our findings implicate that we and others who are using classical mo-DCs for cancer immunotherapy are already vaccinating against RHAMM

Ribonucleic Acid Engineering of Dendritic Cells for Therapeutic Vaccination: Ready ‘N Able to Improve Clinical Outcome?

Targeting and exploiting the immune system has become a valid alternative to conventional options for treating cancer and infectious disease. Dendritic cells (DCs) take a central place given their role as key orchestrators of immunity. Therapeutic vaccination with autologous DCs aims to stimulate the patient’s own immune system to specifically target his/her disease and has proven to be an effective form of immunotherapy with very little toxicity. A great amount of research in this field has concentrated on engineering these DCs through ribonucleic acid (RNA) to improve vaccine efficacy and thereby the historically low response rates. We reviewed in depth the 52 clinical trials that have been published on RNA-engineered DC vaccination, spanning from 2001 to date and reporting on 696 different vaccinated patients. While ambiguity prevents reliable quantification of effects, these trials do provide evidence that RNA-modified DC vaccination can induce objective clinical responses and survival benefit in cancer patients through stimulation of anti-cancer immunity, without significant toxicity. Succinct background knowledge of RNA engineering strategies and concise conclusions from available clinical and recent preclinical evidence will help guide future research in the larger domain of DC immunotherapy

Transcatheter aortic valve durability: a contemporary clinical review

Encouraged by randomized controlled trials demonstrating non-inferiority of transfemoral transcatheter aortic valve implantation (TAVI) compared to surgical aortic valve replacement (SAVR) across all surgical risk categories, there has been a dramatic increase in the use of TAVI in a younger patient cohort with severe aortic stenosis, endorsed by both European and American Cardiac Societies. However, the standard use of TAVI in younger, less co-morbid patients with a longer life expectancy can only be supported if there is sound data demonstrating long-term durability of transcatheter aortic valves (TAVs). In this article, we have reviewed available randomized and observational registry clinical data pertaining to TAV long-term durability, placing emphasis on trials and registries using the new standardized definitions of bioprosthetic valve dysfunction (BVD) and bioprosthetic valve failure (BVF). Despite inherent difficulties in interpreting the available data, the determination reached is that the risk of structural valve deterioration (SVD) is potentially lower after TAVI than SAVR at 5 to 10 years, and that the two treatment modalities have a similar risk of BVF. This supports the adoption of TAVI in younger patients evident in current practice. However, the routine use of TAVI in younger patients with bicuspid aortic valve stenosis should be cautioned due to insufficient long-term TAV durability data in this particular patient population. Finally, we highlight the importance of future research into the unique potential mechanisms that can potentially contribute to TAV degeneration