193 The Achilles VELOSTM Process 2 boosts the dose of highly functional clonal neoantigen-reactive T cells for precision personalized cell therapies

BackgroundAdoptive transfer of ex-vivo expanded tumor-infiltrating lymphocytes (TIL) has shown promise in the clinic. However, the non-specific expansion of TIL and the lack of understanding of the active component of TIL has resulted in poor correlation between clinical response and dose as well as poor understanding of response and resistance mechanisms. The VELOSTM manufacturing process generates a precision and personalized treatment modality by targeting clonal neoantigens with the incorporation of an antigen-specific expansion step to enrich the product for these specificities. Achilles has developed a second generation manufacturing process (VELOSTM Process 2) to boost the neoantigen-reactive cell dose while maintaining key qualitative features associated with function. Here we report the in-depth characterization of clonal neoantigen-reactive T cells (cNeT) products expanded using the two VELOSTM processes.MethodsMatched tumors and peripheral blood from patients undergoing routine surgery were obtained from patients with primary NSCLC or metastatic melanoma (NCT03517917). TIL were expanded from tumor fragments and peptide pools corresponding to the clonal mutations identified using the PELEUSTM bioinformatics platform were synthesized. cNeT were expanded by co-culture of TIL with peptide-pulsed autologous dendritic cells, with an optimized cytokine cocktail and co-stimulation for Process 2. Neoantigen reactivity was assessed using our proprietary potency assay with peptide pool re-challenge followed by intracellular cytokine staining. Single peptide reactivities were identified using ELISPOT and flow cytometric analysis for in-depth phenotyping of cNeT was performed.ResultsCD3+ T cells displayed higher fold expansion in Process 2 (median 77.4) compared to Process 1 (median 3.8)(n=5). Both processes showed similar CD3+ T cell content (median Process 1=91.3%, Process 2=96.9% n=5) and contained both CD4+ and CD8+ T cells showing reactivity to clonal neoantigens. Proportion of cells responding to neoantigen re-challenge was similar across both processes (median Process 1=19.9% and Process 2=18.2%) leading to higher reactive dose when coupled with higher T cell doses in Process 2. Phenotypically T cells were predominantly effector memory for both processes and Process 2 had lower frequencies of terminally differentiated T cells.ConclusionsAchilles’ proprietary potency assay enables the optimization of new processes that deliver high cNeT doses to patients by detecting the active drug component. We have generated proof of concept data that supports the transfer of the VELOSTM Process 2 to clinical manufacture for two first-in-human studies for the treatment of solid cancers.Ethics ApprovalThe samples for the study were collected under an ethically approved protocol (NCT03517917)

New long-horned caddisfly genus and species of Leptoceridae (Insecta: Trichoptera) from Brazil

Ibyacerina caparao new genus, new species (Trichoptera: Leptoceridae) is described and illustrated from specimens collected at Serra do Caparaó, Minas Gerais, Brazil. The monotypic genus is characterized by tibial spur formula 0,2,2; preanal appendages originating from a single base with a median process; tergum X broad, heavily sclerotized, saddle-like, wider at apex, and upturned, bearing small stout setae; inferior appendages each 3-branched, setose; and phallic apparatus tubular, curved slightly ventrad, with pair of lateral processes. Phylogenetic Bayesian and maximum likelihood analyses based on concatenated cytochrome oxidase I (COI) and carbamoyl-phosphate synthetase (CAD) partial sequences (1,504 bp) including representatives of 38 leptocerid genera positioned Ibyacerina gen. nov. with good support within Leptocerinae. However, due to low branch support of most relationships among genera within the clade of Leptocerinae, except Mystacidini, Setodini, and Leptocerini, its close affinities and tribal placement are still unknown.

Redefinition of the sexstrigatus group of Lasioglossum (Hemihalictus) Cockerell, 1897 (Hymenoptera, Apoidea, Halictidae), with a revision of Japanese species

I propose a redefinition of the sexstrigatus group of Lasioglossum (Hemihalictus) Cockerell, 1897, including a phylogenetic analysis. This group is characterised by a combination of the following 12 characteristics: male antenna short, not attaining to metasoma, male labrum with distal process and well-developed basal elevation, male head with genal process as variation, female mesepisternum reticulate-punctate on lower area, mesepisternum without tubercle in both sexes, female metasomal terga with distinct fimbriae on posterior margin, male S8 with well-developed median process, gonobase ventral arm of male genitalia connected with each other at upper ends, gonocoxite of male genitalia smooth, gonostylus of male genitalia small and simple, bud-like, and the ventral retrorse lobe of male genitalia not attaining to gonobase. The Japanese species of the sexstrigatus group are revised. Thirteen species in total are recognised, including three new species: Lasioglossum (Hemihalictus) ikudomei sp. nov., L. (H.) spectrum sp. nov., and L. (H.) subsimplicior sp. nov. Lasioglossum (Hemihalictus) perplexans (Cockerell, 1925) is synonymised under L. (H.) kiautschouense (Strand, 1910). A key to the Japanese species is provided. Bionomical data, such as flight and flower records or habitat, are reported for some species. The distributions of all species are mapped. DNA sequences including a part of the barcode region are given for L. (H.) kiautschouense, L. (H.) ohei Hirashima & Sakagami, 1966, L. (H.) speculinum (Cockerell, 1925), L. (H. ) spectrum sp. nov., L. (H. ) subsimplicior sp. nov., and L. (H. ) taeniolellum (Vachal, 1903).

A new species of Cosmoclopius Stål, 1866 from Argentina (Hemiptera, Reduviidae)

A new species of Cosmoclopius Stål, 1866, C. joceliae sp. nov. is described based on specimens collected in northern Argentina. This new species is recognized by the vertical and truncate median process of pygophore, and the short-recurved spine on the apex of the dorsal phallothecal sclerite; and other features such as the dorsally black head, pronotum, and femora, and the thoracic sterna black with median pale markings; some females show lighter posterior pronotal lobe and femora with more conspicuous dark and pale bands. Digital images of the adult male and female and male genitalia are provided, as well as a comparison with the species of the genus are given.

Ionospheric anomalies associated with the <i>M</i>_w 7.3 Iran–Iraq border earthquake and a moderate magnetic storm

The analysis of the unexpected ionospheric phases before large earthquakes is one of the cutting-edge issues in earthquake prediction studies. In this study, the total electron content (TEC) data from seven International GNSS Service (IGS) stations and the global ionosphere maps (GIMs) were used. Short-time Fourier transform (STFT) and a running median process were applied to the TEC time series to detect abnormalities before the Mw 7.3 Iran–Iraq border earthquake on 12 November 2017. The analyses showed positive anomalies 8–9 d before the earthquake and some positive and negative anomalies 1–6 d before the earthquake. These anomalies were cross-checked using the Kp, Dst, F10.7, Bz component of the interplanetary magnetic field (IMF Bz), electric field (Ey), and plasma speed (VSW) space weather indices. The results showed that the anomalies 1–6 d before the earthquake were caused by a moderate magnetic storm. Moreover, the positive anomalies 8–9 d before the earthquake were likely related to the Iran–Iraq border earthquake due to quiet space weather, local dispersion, and the proximity to the epicenter.

Ionospheric Anomalies Associated with Mw7.3 Iran-Iraq Border Earthquake and a Moderate Magnetic Storm

The analysis of the unexpected ionospheric phases before large earthquakes is a popular approach in earthquake prediction studies. In this study, the Total Electron Content (TEC) data of five International GNSS Service (IGS) stations and the Global Ionosphere Maps (GIMs) were used. The Short-time Fourier Transform (STFT) and a running median process were applied on the TEC time series to detect abnormalities before the Mw7.3 Iran-Iraq border earthquake on November 12, 2017. The analyzes showed positive anomalies 8–9 days before the earthquake and some positive/negative anomalies 1–6 days before the earthquake. These anomalies were cross-checked by space weather indices Kp, Dst, F10.7, Bz component of the interplanetary magnetic field (IMF Bz), electric field (Ey), and plasma speed (VSW). The results showed that the anomalies 1–6 days before the earthquake caused by a moderate magnetic storm. Also, the positive anomalies 8–9 days before the earthquake should be related to the Iran-Iraq border earthquake due to quiet space weather, local dispersion, and proximity to the epicenter.

A new species of Passandra Dalman (Coleoptera: Passandridae) from the Philippines and Borneo

Passandra barsevskisi sp. nov. (Coleoptera: Passandridae) is described and illustrated from Borneo and the Philippines. The new species can be distinguished from all known species of Passandra by the following combination of features: head, pronotum and elytra black; antennomeres 3–10 with narrow groove ventrally, male antennae robust with antennomeres 4–10 swollen; admedian grooves of head deep, long, almost straight, slightly diverging anteriorly; median process of head well developed and reaching occipital groove; pronotal disc with two deep and long admedian grooves; pronotal sublateral lines entire, widely separated anteriorly; submarginal basal groove deeply and narrowly emarginate medially in male, notched in female; each elytron with lines I and VI complete, lines II and V incomplete; and median lobe of aedeagus with triangular apical portion and rounded apex.

Dealing with a hairy beast–larval morphology and chaetotaxy of the Australian endemic diving beetle genus Spencerhydrus (Coleoptera, Dytiscidae, Cybistrini)

In this contribution, the larval morphology of Spencerhydrus Sharp, 1882 was studied, an Australian endemic genus in the diving beetle tribe Cybistrini. All instars of the only two species included in the genus (S. latecinctus Sharp, 1882 and S. pulchellus Sharp, 1882) are described and illustrated with the exception of the third instar of S. latecinctus. Detailed morphometric and primary chaetotaxic analyses were performed to discover useful characters for generic diagnosis and species distinction. Spencerhydrus can be distinguished from other Cybistrini genera by the medial projection of frontoclypeus slightly indented apically, with lamellae clypeales directed forward in a characteristic V-shaped pattern, the median process of prementum strongly developed, the presence of a single ventral sclerite on prothorax, the presence of basoventral spinulae on claws, and the reduced sclerotization of the abdominal segment VII which covers only the anterior half. Larvae of the two species of Spencerhydrus can readily be distinguished by the shape of the median process of prementum, which is visibly broader in S. pulchellus than in S. latecinctus.

Contribution to the knowledge of the oribatid mite genus Zeasuctobelba (Acari, Oribatida, Suctobelbidae)

A new species of Zeasuctobelba (Oribatida, Suctobelbidae) is described from a moss Sphagnum magellanicum in swamp in southern Chile. Zeasuctobelba processa sp. nov. differs from all species of the genus by the presence of a median process on the anterior margin of the ventral plate (anterior part of epimere I), lateral sides of prodorsum with one pair of strong triangular processes and by bothridial setae having long setiform apices and long cilia. Revised generic diagnosis, identification key and data on distribution of known species of Zeasuctobelba are presented. Zeasuctobelba nodosa Hammer, 1966 and Z. arcuata Hammer, 1968 are excluded from Zeasuctobelba.