Id-neoantigen vaccine induces therapeutic CD8+ T cells against multiple myeloma: H chain-loss escapees cause FLC MM.

BACKGROUND: Multiple myeloma (MM) cancers originate from plasma cells that have passed through the germinal center reaction where somatic hypermutation of Ig V regions takes place. Myeloma protein V regions often express many mutations and are thus a rich source of neoantigens (traditionally called idiotopes (Id)). Therefore, these are highly tumor-specific and excellent targets for immunotherapy. METHODS: We have developed a DNA Id vaccine which as translated protein targets conventional dendritic cells (cDC) for CCL3-mediated delivery of myeloma protein V regions in a single-chain fragment variable (scFv) format. Vaccine efficacy was studied in the mouse MM model, mineral oil-induced plasmacytoma 315.BM. RESULTS: The Id vaccine protected mice against a challenge with MM cells. Moreover, the vaccine had a therapeutic effect. However, in some of the vaccinated mice, MM cells not producing H chains escaped rejection, resulting in free light chain (FLC) MM. Depletion of CD8+ T cells abrogated vaccine efficacy, and protection was observed to be dependent on cDC1s, using Batf3-/- mice. Modifications of scFv in the vaccine demonstrated that CD8+ T cells were specific for two mutated VH sequences. CONCLUSIONS: VH neoantigen-specific CD8+ T cells elicited by CCL3-containing Id vaccines had a therapeutic effect against MM in a mouse model. MM cells could escape rejection by losing expression of the H chain, thus giving rise to FLC MM.

Electromagnetic field-based navigation for percutaneous punctures on C-arm CT: experimental evaluation and clinical application.

The aim of this study was to prospectively evaluate the needle visualization and placement error and use of an electromagnetic field-based tracking navigation device for puncture procedures based on C-arm CT (CACT) images. A commercially available navigation device was mounted on an angiographic X-ray system setup for CACT. After the target was defined, needle placement was performed under real-time visualization of the virtual needle in CACT images. The final, real needle position was assessed by CACT. Punctures were performed in phantoms (n = 76) and in twelve patients (eight biopsies, three drainages, one injection). Procedure times, system error, user error and total error were assessed. In phantoms, mean total error was 2.3 +/- 0.9 mm, user error was 1.4 +/- 0.8 mm and system error was 1.7 +/- 0.8 mm. In the patient study, the targeted puncture was successful in all twelve cases. The mean total error was 5.4 mm +/- 1.9 mm (maximum 8.1 mm), user error was 3.7 +/- 1.7 mm, system error was 3.2 +/- 1.4 mm and mean skin-to-target time was less than 1 min. The navigation device relying on CACT was accurate in terms of needle visualization and useful for needle placement under both experimental and clinical conditions. For more complex procedures, electromagnetic field-based tracking guidance might be of help in facilitating the puncture and reducing both the puncture risk and procedure time.