Comminution Characteristics of Lithium Bearing Mica Ores From Different Devices

This paper highlights on the comminution and to the lesser extent liberation properties of two greisen-type lithium bearing-mica ores (L1, L2) subjected to different breakage devices; cone crusher (CC), roller crusher (RC), rotor beater mill (RBM) and a screen mill (SM). The particle size distributions (PSD) of the products from each device were evaluated to search for an appropriate PSD model using Gates-Gaudin-Schuhmann (GGS) and Rosin-Rammler (RR) functions. To determine an appropriate function, coefficients of determination (R2 ) were used as a criterion. Due to budget constraint, only products from rotor beater mill (RBM) were examined for mineral liberation by an automated scanning electron microscope (SEM) technique. It was found that RBM, RC and SM products were better described by the RR model than the GGS model with higher R2 values of 0.97 to 1.0. However, cone crusher products for L1 were better described by GSS model, while that for L2 were better described by RR model. In terms of the spread of size distribution as indicated by RR model parameters, RC products were more uniformly distributed compared to those from other devices, for both ores. Also the RBM products were more scattered than those from other devices. The results indicate that the composition of individual ores affected the comminution products PSDs as different PSD model parameters were obtained for samples comminuted by same devices. The modal mineralogy indicated that both ores are rich in quartz, topaz, zinnwaldite and muscovite. Furthermore, the result indicates that, for both ores, the zinnwaldite phase is more enriched in the fraction < 250 µm. Moreover, better liberation of zinnwaldite is observed for L1 compared to L2. This could be explained by differences of the two ores in three aspects; the nature of mineral association, reduction ratio of the fractions analysed and the spread of the size distribution

90-yttrium-ibritumomab tiuxetan as first-line treatment for follicular lymphoma: updated efficacy and safety results at an extended median follow-up of 9.6 years

Radioimmunotherapy with 90-yttrium-ibritumomab tiuxetan (90Y-IT) as first-line treatment in patients with follicular lymphoma (FL) demonstrated promising results with a complete remission (CR) rate of 56% and a median progression-free survival (PFS) of 26 months, when initially analyzed after a median follow-up of 30.6 months. The aim of this long-term follow-up was to investigate whether clinical benefits were maintained and new safety signals appeared. Fifty-nine patients, aged ≥ 50 years, with FL grade 1 to 3A in stages II to IV were treated with 90Y-IT as first-line therapy. If CR without evidence of minimal residual disease (MRD), partial response or stable disease was achieved 6 months after treatment, patients were observed without further treatment. Patients with CR but persisting MRD received consolidation therapy with rituximab. The primary endpoint was the clinical response rate. Secondary endpoints were time to progression, safety, and tolerability. After a median follow-up of 9.6 years, median PFS was 3.6 years, and 8-year PFS was 38.3%. Median overall survival (OS) was not reached during the extended follow-up, and 8-year OS amounted to 69.2%. Age 65 years and above or disease progression within 24 months of treatment were significantly associated with shorter OS. An important finding was the lack of new safety signals. In particular, no increase in secondary malignancies or transformation into aggressive lymphoma was observed compared to trials with a similar follow-up. In summary, 90Y-IT as first-line treatment demonstrates a favorable safety profile and long-term clinical activity in a substantial fraction of FL patients in need of therapy

High-affinity T-cell receptor specific for MyD88 L265P mutation for adoptive T-cell therapy of B-cell malignancies

BACKGROUND: Adoptive transfer of engineered T cells has shown remarkable success in B-cell malignancies. However, the most common strategy of targeting lineage-specific antigens can lead to undesirable side effects. Also, a substantial fraction of patients have refractory disease. Novel treatment approaches with more precise targeting may be an appealing alternative. Oncogenic somatic mutations represent ideal targets because of tumor specificity. Mutation-derived neoantigens can be recognized by T-cell receptors (TCRs) in the context of MHC-peptide presentation. METHODS: Here we have generated T-cell lines from healthy donors by autologous in vitro priming, targeting a missense mutation on the adaptor protein MyD88, changing leucine at position 265 to proline (MyD88 L265P), which is one of the most common driver mutations found in B-cell lymphomas. RESULTS: Generated T-cell lines were selectively reactive against the mutant HLA-B*07:02-restricted epitope but not against the corresponding wild-type peptide. Cloned TCRs from these cell lines led to mutation-specific and HLA-restricted reactivity with varying functional avidity. T cells engineered with a mutation-specific TCR (TCR-T cells) recognized and killed B-cell lymphoma cell lines characterized by intrinsic MyD88 L265P mutation. Furthermore, TCR-T cells showed promising therapeutic efficacy in xenograft mouse models. In addition, initial safety screening did not indicate any sign of off-target reactivity. CONCLUSION: Taken together, our data suggest that mutation-specific TCRs can be used to target the MyD88 L265P mutation, and hold promise for precision therapy in a significant subgroup of B-cell malignancies, possibly achieving the goal of absolute tumor specificity, a long sought-after dream of immunotherapy

Isolation of neoantigen-specific human T cell receptors from different human and murine repertoires

(1) Background: Mutation-specific T cell receptor (TCR)-based adoptive T cell therapy represents a truly tumor-specific immunotherapeutic strategy. However, isolating neoepitope-specific TCRs remains a challenge. (2) Methods: We investigated, side by side, different TCR repertoires-patients' peripheral lymphocytes (PBLs) and tumor-infiltrating lymphocytes (TILs), PBLs of healthy donors, and a humanized mouse model-to isolate neoepitope-specific TCRs against eight neoepitope candidates from a colon cancer and an ovarian cancer patient. Neoepitope candidates were used to stimulate T cells from different repertoires in vitro to generate neoepitope-specific T cells and isolate the specific TCRs. (3) Results: We isolated six TCRs from healthy donors, directed against four neoepitope candidates and one TCR from the murine T cell repertoire. Endogenous processing of one neoepitope, for which we isolated one TCR from both human and mouse-derived repertoires, could be shown. No neoepitope-specific TCR could be generated from the patients' own repertoire. (4) Conclusion: Our data indicate that successful isolation of neoepitope-specific TCRs depends on various factors such as the heathy donor's TCR repertoire or the presence of a tumor microenvironment allowing neoepitope-specific immune responses of the host. We show the advantage and feasibility of using healthy donor repertoires and humanized mouse TCR repertoires to generate mutation-specific TCRs with different specificities, especially in a setting when the availability of patient material is limited

90-yttrium-ibritumomab tiuxetan as first-line treatment for follicular lymphoma: updated efficacy and safety results at an extended median follow-up of 9.6 years

Radioimmunotherapy with 90-yttrium-ibritumomab tiuxetan (90Y-IT) as first-line treatment in patients with follicular lymphoma (FL) demonstrated promising results with a complete remission (CR) rate of 56% and a median progression-free survival (PFS) of 26 months, when initially analyzed after a median follow-up of 30.6 months. The aim of this long-term follow-up was to investigate whether clinical benefits were maintained and new safety signals appeared. Fifty-nine patients, aged ≥ 50 years, with FL grade 1 to 3A in stages II to IV were treated with 90Y-IT as first-line therapy. If CR without evidence of minimal residual disease (MRD), partial response or stable disease was achieved 6 months after treatment, patients were observed without further treatment. Patients with CR but persisting MRD received consolidation therapy with rituximab. The primary endpoint was the clinical response rate. Secondary endpoints were time to progression, safety, and tolerability. After a median follow-up of 9.6 years, median PFS was 3.6 years, and 8-year PFS was 38.3%. Median overall survival (OS) was not reached during the extended follow-up, and 8-year OS amounted to 69.2%. Age 65 years and above or disease progression within 24 months of treatment were significantly associated with shorter OS. An important finding was the lack of new safety signals. In particular, no increase in secondary malignancies or transformation into aggressive lymphoma was observed compared to trials with a similar follow-up. In summary, 90Y-IT as first-line treatment demonstrates a favorable safety profile and long-term clinical activity in a substantial fraction of FL patients in need of therapy. ClinicalTrials.gov Identifier: NCT00772655

A Multispecialty Evaluation of Thiel Cadavers for Surgical Training

Background: Changes in UK legislation allow for surgical procedures to be performed on cadavers. The aim of this study was to assess Thiel cadavers as high-fidelity simulators and to examine their suitability for surgical training. Methods: Surgeons from various specialties were invited to attend a 1 day dissection workshop using Thiel cadavers. The surgeons completed a baseline questionnaire on cadaveric simulation. At the end of the workshop, they completed a similar questionnaire based on their experience with Thiel cadavers. Comparing the answers in the pre- and post-workshop questionnaires assessed whether using Thiel cadavers had changed the surgeons’ opinions of cadaveric simulation. Results: According to the 27 participants, simulation is important for surgical training and a full-procedure model is beneficial for all levels of training. Currently, there is dissatisfaction with existing models and a need for high-fidelity alternatives. After the workshop, surgeons concluded that Thiel cadavers are suitable for surgical simulation (p = 0.015). Thiel were found to be realistic (p < 0.001) to have reduced odour (p = 0.002) and be more cost-effective (p = 0.003). Ethical constraints were considered to be small. Conclusion: Thiel cadavers are suitable for training in most surgical specialties