Patients with cancer experience higher burden of SARS-CoV-2 infection, disease severity, complications, and mortality, than the general population. SARS-CoV-2 mRNA vaccines are highly effective in the general population; however, few data are available on their efficacy in patients with cancer. Using a prospective cohort, we assessed the seroconversion rates and anti-SARS-CoV-2 spike protein antibody titers following the 1
st
and 2
nd
dose of BNT162b2 and mRNA-1273 SARS-CoV-2 vaccines in patients with cancer in U.S. and Europe from January to April 2021. Among 131 patients, most (94%) achieved seroconversion after receipt of 2 vaccine doses. Seroconversion rates and antibody titers in patients with hematological malignancy were significantly lower than those with solid tumors. None of the patients with history of anti-CD-20 antibody in the 6 months prior to vaccination developed antibody response. Antibody titers were highest for clinical surveillance or endocrine therapy groups and lowest for cytotoxic chemotherapy or monoclonal antibody group.
Size is the key regulating the crystalline structure of iron oxide nanoparticles. The effect of the crystal size on the microstructure of these nanoparticles was investigated in an aqueous dilute suspension by energy dispersive X-ray diffraction (EDXD) and in an aqueous concentrated suspension by X-ray powder diffraction (XRD), at 293 K. Nanoparticle structure was also investigated by HRTEM. Structural results were interpreted in terms of theoretical models built using structural parameters obtained by the Rietveld method on XRD. The ability of the pair distribution function (PDF) to measure medium-range correlation lengths and size in nanoscale crystalline materials was also investigated and discussed. The sensitivity of the PDF technique allowed modelling of sample polydispersity
Ultrasmall superparamagnetic iron oxide (USPIO) particles were structurally characterized in situ in an aqueous dilute suspension by energy dispersive X-ray diffraction (EDXD) and ex situ as powders obtained by lyophilization of the suspension by angular dispersive X-ray diffraction (ADXD) at 20 degrees C. Structural parameters obtained by the Rietveld method on ADXD data were used as starting parameters for modeling the structure of the particles in suspension. Although each particle is a single crystal, as evidenced by conventional X-ray diffraction, our results indicate that the structural order, specific to a crystal, does not extend to the entire volume of the particle. In fact, each individual particle, averagely, has a crystalline structural extension ca. 4.0 nm smaller than the apparent dimensions obtained by both ADXD and TEM (ca. 8.0 nm).
Background
Reshaping the tumor microenvironment by novel immunotherapies represents a key strategy to improve cancer treatment. Nevertheless, responsiveness to these treatments is often correlated with the extent of T cell infiltration at the tumor site. Remarkably, microsatellite stable rectal cancer is characterized by poor T cell infiltration and, therefore, does not respond to immune checkpoint blockade. To date, the only available curative option for these patients relies on extensive surgery. With the aim to broaden the application of promising immunotherapies, it is necessary to develop alternative approaches to promote T cell infiltration into the tumor microenvironment of these tumors. In this regard, recent evidence shows that radiotherapy has profound immunostimulatory effects, hinting at the possibility of combining it with immunotherapy. The combination of long-course chemoradiotherapy and immune checkpoint inhibition was recently shown to be safe and yielded promising results in rectal cancer, however short-course radiotherapy and immune checkpoint inhibition have never been tested in these tumors.
Methods
Our clinical trial investigates the clinical and biological impact of combining pembrolizumab with short-course radiotherapy in the neo-adjuvant treatment of localized rectal cancer. This phase II non-randomized study will recruit 25 patients who will receive short-course preoperative radiotherapy (5 Gy × 5 days) and four injections of pembrolizumab starting on the same day and on weeks 4, 7 and 10. Radical surgery will be performed three weeks after the last pembrolizumab injection. Our clinical trial includes an extensive translational research program involving the transcriptomic and proteomic analysis of tumor and blood samples throughout the course of the treatment.
Discussion
Our study is the first clinical trial to combine short-course radiotherapy and immune checkpoint inhibition in rectal cancer, which could potentially result in a major breakthrough in the treatment of this cancer. Additionally, the translational research program will offer insights into immunological changes within the tumor and blood and their correlation with patient outcome. Taken together, our work will help optimizing future treatment combinations and, possibly, better selecting patients.
Trial registration
This study was registered with www.clinicaltrial.gov: NCT04109755. Registration date: June, 2020.
BackgroundReshaping the tumor microenvironment by novel immunotherapies represents a key strategy to improve the treatment of cancers. Nevertheless, responsiveness to these treatments is often correlated with the extent of the T cell infiltration at the tumor site. Remarkably, microsatellite stable rectal cancer is characterized by poor infiltration and, therefore, do not respond to immune checkpoint blockade. To date, the only available curative option for these patients relies on extensive surgery. With the aim to broaden the application of promising immunotherapies, it is necessary to develop alternative approaches to promote T cell infiltration into the tumor microenvironment of these tumors. In this regard, recent evidence shows that radiotherapy may have profound immunostimulatory effects, hinting at the possibility of combining it with immunotherapy. The combination of long-course chemoradiotherapy and immunotherapy was recently shown to be safe and yielded promising results in rectal cancer, however short-course radiotherapy and immunotherapy have never been tested in these tumors.MethodsOur clinical trial investigates the clinical and biological impact of combining pembrolizumab with short-course radiotherapy in the neo-adjuvant treatment of localized microsatellite stable rectal cancer. This phase II non-randomized study will recruit 25 patients who will receive short-course preoperative radiotherapy (5Gy x 5 days) and four injections of pembrolizumab starting on the same day and on weeks 4, 7 and 10. Radical surgery will be performed after three weeks from the last pembrolizumab injection. Our clinical trial also includes an extensive research program involving the transcriptomic and proteomic analysis of blood and tumor samples throughout the course of the treatment.DiscussionOur study is the first clinical trial to provide with safety and efficacy information of this novel treatment approach in rectal cancer, leading to a major breakthrough in the treatment of this cancer. Additionally, the translational research program will offer better insight into immunological changes within the tumor and blood during treatment. Taken together, our work will help optimizing future treatment combinations and, possibly, better selecting patients.Trial registrationThis study was registered with www.clinicaltrial.gov: NCT04109755. Registration date: June, 2020.
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