Treating patients who have cancer with vaccines that stimulate a targeted immune response is conceptually appealing, but cancer vaccine trials have not been successful in late-stage patients with ...treatment-refractory tumours
. We are testing melanoma FixVac (BNT111)-an intravenously administered liposomal RNA (RNA-LPX) vaccine, which targets four non-mutated, tumour-associated antigens that are prevalent in melanoma-in an ongoing, first-in-human, dose-escalation phase I trial in patients with advanced melanoma (Lipo-MERIT trial, ClinicalTrials.gov identifier NCT02410733). We report here data from an exploratory interim analysis that show that melanoma FixVac, alone or in combination with blockade of the checkpoint inhibitor PD1, mediates durable objective responses in checkpoint-inhibitor (CPI)-experienced patients with unresectable melanoma. Clinical responses are accompanied by the induction of strong CD4
and CD8
T cell immunity against the vaccine antigens. The antigen-specific cytotoxic T-cell responses in some responders reach magnitudes typically reported for adoptive T-cell therapy, and are durable. Our findings indicate that RNA-LPX vaccination is a potent immunotherapy in patients with CPI-experienced melanoma, and suggest the general utility of non-mutant shared tumour antigens as targets for cancer vaccination.
We investigated the applicability and feasibility of perceptive computing assisted gait analysis in multiple sclerosis (MS) patients using Microsoft Kinect™. To detect the maximum walking speed and ...the degree of spatial sway, we established a computerized and observer-independent measure, which we named Short Maximum Speed Walk (SMSW), and compared it to established clinical measures of gait disability in MS, namely the Expanded Disability Status Scale (EDSS) and the Timed 25-Foot Walk (T25FW).
Cross-sectional study of 22 MS patients (age mean ± SD 43 ± 9 years, 13 female) and 22 age and gender matched healthy control subjects (HC) (age 37 ± 11 years, 13 female). The disability level of each MS patient was graded using the EDSS (median 3.0, range 0.0-6.0). All subjects then performed the SMSW and the Timed 25-Foot Walk (T25FW). The SMSW comprised five gait parameters, which together assessed average walking speed and gait stability in different dimensions (left/right, up/down and 3D deviation).
SMSW average walking speed was slower in MS patients (1.6 ± 0.3 m/sec) than in HC (1.8 ± 0.4 m/sec) (p = 0.005) and correlated well with EDSS (Spearman's Rho 0.676, p < 0.001). Furthermore, SMSW revealed higher left/right deviation in MS patients compared to HC. SMSW showed high recognition quality and retest-reliability (covariance 0.13 m/sec, ICC 0.965, p < 0.001). There was a significant correlation between SMSW average walking speed and T25FW (Pearson's R = -0.447, p = 0.042).
Our data suggest that ambulation tests using Microsoft Kinect™ are feasible, well tolerated and can detect clinical gait disturbances in patients with MS. The retest-reliability was on par with the T25FW.
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