Host and habitat shape ectoparasite diversity on and (Muridae).

and are commensal rodent species endemic to Africa. A recent taxonomic revision within leaves the parasite–host list of questionable and that of incomplete. The current study aimed to develop a better understanding of the ectoparasite diversity associated with the 2 distinct but closely related rodent species and to explore the influence of host and habitat type on ectoparasite infestations.

Intra- and interspecific variation of Amblyomma ticks from southern Africa.

Background: Amblyomma spp. ticks, known for their long mouthparts, bright ornate appearance and aggressive hunting behaviour, are vectors of a number of important pathogens. In southern Africa, 17 Amblyomma spp.

Novel OX40 and 4-1BB derived spacers enhance CD30 CAR activity and safety in CD30 positive lymphoma models.

The chimeric antigen receptor (CAR) derived from the CD30 specific murine antibody, HRS-3, has produced promising clinical efficacy with a favorable safety profile in the treatment of relapsed or refractory CD30-positive lymphomas. However, persistence of the autologous CAR-T cells was brief, and many patients relapsed a year after treatment. The lack of persistence may be attributed to the use of a wild-type immunoglobulin (Ig)G1 spacer that can associate with Fc receptors.

Overexpression of an Engineered SERPINB9 Enhances Allogeneic T-cell Persistence and Efficacy.

Allogeneic chimeric antigen receptor (CAR)-expressing T cells offer many advantages over autologous therapies, but their benefits are curtailed by graft-versus-host disease and elimination by recipient immune cells. Moreover, just as with autologous therapies, allogeneic CAR T cells are susceptible to activation-induced cell death (AICD) caused by chronic antigen exposure (CAE). Granzyme B- and Fas/Fas ligand-initiated caspase-mediated apoptoses are key mechanisms of T-cell death caused by T/NK cell-mediated allorejection or CAE.

Ecto- and endoparasites of common reedbuck, , at 2 localities in KwaZulu-Natal Province, South Africa: community and network structure.

Parasite community structure is governed by functional traits of hosts and parasites. Notably, parasite populations and communities respond to host social and spatial behaviour. Many studies demonstrating these effects dealt with small-bodied host species, while the influence of host social patterns on parasite communities in large hosts remains understudied.

B7-H3-Targeting Chimeric Antigen Receptors Epstein-Barr Virus-specific T Cells Provides a Tumor Agnostic Off-The-Shelf Therapy Against B7-H3-positive Solid Tumors.

Unlabelled: Encouraged by the observations of significant B7-H3 protein overexpression in many human solid tumors compared to healthy tissues, we directed our focus towards targeting B7-H3 using chimeric antigen receptor (CAR) T cells. We utilized a nanobody as the B7-H3-targeting domain in our CAR construct to circumvent the stability issues associated with single-chain variable fragment-based domains. In efforts to expand patient access to CAR T-cell therapy, we engineered our nanobody-based CAR into human Epstein-Barr virus-specific T cells (EBVST), offering a readily available off-the-shelf treatment.

Searching for common patterns in parasite ecology: species and host contributions to beta-diversity in helminths of South African ungulates and fleas of South American rodents.

We searched for common patterns in parasite ecology by investigating species and host contributions to the beta-diversity of infracommunities (=assemblages of parasites harboured by a host individual) in helminths of three species of South African ungulates and fleas of 11 species of South American rodents, assuming that a comparison of patterns in distinctly different parasites and hosts would allow us to judge the generality or, at least, commonness of these patterns. We used data on species' composition and numbers of parasites and asked whether (i) parasite species' attributes (life cycle, transmission mode, and host specificity in helminths; possession of sclerotized combs, microhabitat preference, and host specificity in fleas) or their population structure (mean abundance and/or prevalence) and (ii) host characteristics (sex and age) affect parasite and host species' contributions to parasite beta-diversity (SCBD and HCBD, respectively). We found that parasite species' morphological and ecological attributes were mostly not associated with their SCBD.

Sympatry of Amblyomma eburneum and Amblyomma variegatum on African buffaloes and prevalence of pathogens in ticks.

The Amblyomma genus is represented on the African continent by 24 species, out of which 17 are known to occur in different ecological niches of southern Africa. Amblyomma, known for their aggressive hunting behaviour and aptitude as pathogen vectors, are of main concern to travellers, mainly in rural and conservation areas of Africa. In this study, we highlight the overlapping distribution of Amblyomma eburneum and Amblyomma variegatum found on African buffaloes (Syncerus caffer) at Coutada 11, Central Mozambique.

Nestedness and beta diversity of gastrointestinal helminth communities in common warthogs, (Suidae), at 2 localities in South Africa.

Few studies have investigated the ecological interactions between wild species of Suidae and their parasites, leaving our knowledge concerning this host–parasite system fragmented. In the present study, we applied network studies to analyse community nestedness in helminth assemblages of common warthogs, (Gmelin) (Suidae). Helminth data were compiled from 95 warthogs, including young and adult males and females, from 2 different conservation areas in Mpumalanga and Limpopo Provinces, South Africa, collected monthly over a period of 1 year each.

Ectoparasites associated with the Bushveld gerbil () and the role of the host and habitat in shaping ectoparasite diversity and infestations.

Rodents are known hosts for various ectoparasite taxa such as fleas, lice, ticks and mites. South Africa is recognized for its animal diversity, yet little is published about the parasite diversity associated with wild rodent species. By focusing on a wildlife-human/domestic animal interface, the study aims to record ectoparasite diversity and levels of infestations of the Bushveld gerbil, , and to establish the relationship between ectoparasite infestation parameters and host- and habitat factors.

Impact of host sex and age on the diversity of endoparasites and structure of individual-based host-parasite networks in nyalas (Tragelaphus angasii Angas) from three game reserves in KwaZulu-Natal province, South Africa.

In recent years, numerous studies have examined the effect of host sex and age on the structure of parasite communities in several host taxa under various environmental conditions and in different geographic regions. However, the influence of such factors on the structure of host-parasite networks has received less attention, and remarkably few studies have been carried out on large terrestrial mammals. In this study, we investigated the effects of host age and sex on the parasite infra- and component communities of nyalas (Tragelaphus angasii) and on the structure of individual-based nyala-endoparasite networks.

Similarity in ixodid tick communities harboured by wildlife and livestock in the Albany Thicket Biome of South Africa.

South Africa has a diverse fauna of ixodid tick species, several of which are of medical or veterinary importance. Elucidation of which host or environmental characteristics determine the composition and abundance of tick assemblages is, therefore, highly relevant to disease management and wildlife conservation efforts. Here, we analysed the similarity in ixodid tick assemblages of three wildlife and three livestock species in a natural (Great Fish River Reserve) and anthropogenic (an adjacent farm) habitat in South Africa.

First-in-human trial exploring safety, antitumor activity, and pharmacokinetics of Sym013, a recombinant pan-HER antibody mixture, in advanced epithelial malignancies.

Purpose: Sym013 contains six humanized monoclonal antibodies that bind to non-overlapping epitopes on three human epidermal growth factor receptors (HER1-3). Preclinical studies suggested Sym013 strongly suppresses growth of multiple epithelial tumors. This is a first-in-human study exploring safety and efficacy of Sym013 in patients with advanced epithelial malignancies.

Paediatric Strategy Forum for medicinal product development of chimeric antigen receptor T-cells in children and adolescents with cancer: ACCELERATE in collaboration with the European Medicines Agency with participation of the Food and Drug Administration.

The seventh multi-stakeholder Paediatric Strategy Forum focused on chimeric antigen receptor (CAR) T-cells for children and adolescents with cancer. The development of CAR T-cells for patients with haematological malignancies, especially B-cell precursor acute lymphoblastic leukaemia (BCP-ALL), has been spectacular. However, currently, there are scientific, clinical and logistical challenges for use of CAR T-cells in BCP-ALL and other paediatric malignancies, particularly in acute myeloid leukaemia (AML), lymphomas and solid tumours.

Adaptive radiation and speciation in Rhipicephalus ticks: A medley of novel hosts, nested predator-prey food webs, off-host periods and dispersal along temperature variation gradients.

Rhipicephalus are a species-diverse genus of ticks, mainly distributed in the Afrotropics with some species in the Palearctic and Oriental regions. Current taxonomic consensus comprise nine informal species groups/lineages based on immature morphology. This work integrates biogeographic, ecological and molecular lines of evidence to better understand Rhipicephalus evolution.

Some gastrointestinal nematodes and ixodid ticks shared by several wildlife species in the Kruger National Park, South Africa.

Parasite surveys were conducted for 1–2 years in the Kruger National Park (KNP), South Africa on blue wildebeest, impalas, greater kudus, common warthogs and scrub hares. The host associations of some of the gastrointestinal nematode species infecting ≥60% of at least one of the five host species, were determined. These were Agriostomum gorgonis, Cooperia acutispiculum, Cooperia connochaeti, Cooperia hungi, Cooperia neitzi, Cooperioides hamiltoni, Gaigeria pachyscelis, Haemonchus bedfordi, Haemonchus krugeri, Haemonchus vegliai, Impalaia tuberculata, Longistrongylus sabie, Strongyloides papillosus, Trichostrongylus deflexus and Trichostrongylus thomasi.

Deep neural networks identify signaling mechanisms of ErbB-family drug resistance from a continuous cell morphology space.

It is well known that the development of drug resistance in cancer cells can lead to changes in cell morphology. Here, we describe the use of deep neural networks to analyze this relationship, demonstrating that complex cell morphologies can encode states of signaling networks and unravel cellular mechanisms hidden to conventional approaches. We perform high-content screening of 17 cancer cell lines, generating more than 500 billion data points from ∼850 million cells.

Ticks and tick-borne pathogens infecting livestock and dogs in Tchicala-Tcholoanga, Huambo Province, Angola.

The diversity of ticks and tick-borne pathogens (TBPs) infesting domestic animals in Tchicala-Tcholoanga, Angola, in 2016 was investigated. Seventeen tick species were recorded, Amblyomma pomposum being the most abundant on cattle (40%), goats (38%) and sheep (35%); Rhipicephalus turanicus was the most abundant on dogs (46%). This study presents new records of Haemaphysalis paraleachi, R.

Colorectal cancer residual disease at maximal response to EGFR blockade displays a druggable Paneth cell-like phenotype.

Blockade of epidermal growth factor receptor (EGFR) causes tumor regression in some patients with metastatic colorectal cancer (mCRC). However, residual disease reservoirs typically remain even after maximal response to therapy, leading to relapse. Using patient-derived xenografts (PDXs), we observed that mCRC cells surviving EGFR inhibition exhibited gene expression patterns similar to those of a quiescent subpopulation of normal intestinal secretory precursors with Paneth cell characteristics.

Simultaneous targeting of HER family pro-survival signaling with Pan-HER antibody mixture is highly effective in TNBC: a preclinical trial with PDXs.

Background: The human epidermal growth factor receptor (HER) family, notably EGFR, is overexpressed in most triple-negative breast cancer (TNBC) cases and provides cancer cells with compensatory signals that greatly contribute to the survival and development of resistance in response to therapy. This study investigated the effects of Pan-HER (Symphogen, Ballerup, Denmark), a novel mixture of six monoclonal antibodies directed against members of the HER family EGFR, HER2, and HER3, in a preclinical trial of TNBC patient-derived xenografts (PDXs).

Methods: Fifteen low passage TNBC PDX tumor samples were transferred into the right mammary fat pad of mice for engraftment.

Invasive cattle ticks in East Africa: morphological and molecular confirmation of the presence of Rhipicephalus microplus in south-eastern Uganda.

Background: Rhipicephalus microplus, an invasive tick species of Asian origin and the main vector of Babesia species, is considered one of the most widespread ectoparasites of livestock. The tick has spread from its native habitats on translocated livestock to large parts of the tropical world, where it has replaced some of the local populations of Rhipicephalus decoloratus ticks. Although the tick was reported in Uganda 70 years ago, it has not been found in any subsequent surveys.

CD4 and CD8a PET imaging predicts response to novel PD-1 checkpoint inhibitor: studies of Sym021 in syngeneic mouse cancer models.

Predicting the outcome of immunotherapy is essential for efficient treatment. The recent clinical success of immunotherapy is increasingly changing the paradigm of cancer treatment. Accordingly, the development of immune-based agents is accelerating and the number of agents in the global immuno-oncology pipeline has grown 60-70% over the past year.

Ixodid ticks (Acari: Ixodidae) collected from African savanna elephants (Loxodonta africana) and African forest elephants (Loxodonta cyclotis).

Eight ixodid tick species were collected from 173 African savanna elephants (Loxodonta africana) in Kenya, northern Mozambique and Zimbabwe, and two species were collected from six African forest elephants (Loxodonta cyclotis) in the Republic of Congo. A new host record is reported for Amblyomma eburneum. A list of ticks collected from elephants in various African countries, and stored in the United States National Tick Collection, is supplied as well as an annotated checklist of the 27 ixodid tick species that have been collected from African elephants.

Sym021, a promising anti-PD1 clinical candidate antibody derived from a new chicken antibody discovery platform.

Discovery of therapeutic antibodies is a field of intense development, where immunization of rodents remains a major source of antibody candidates. However, high orthologue protein sequence homology between human and rodent species disfavors generation of antibodies against functionally conserved binding epitopes. Chickens are phylogenetically distant from mammals.

Identity of Haemaphysalis (Rhipistoma) muhsamae Santos Dias, 1954 (Acari: Ixodidae) and H. (R.) subterra Hoogstraal, El Kammah & Camicas, 1992, parasites of carnivores and rodents in eastern and southern Africa.

Haemaphysalis (Rhipistoma) muhsamae Santos Dias, 1954 (Acari: Ixodidae) and H. (R.) subterra Hoogstraal, El Kammah & Camicas, 1992, are redescribed based on males and females.