First-in-human phase I/IIa trial to evaluate the safety and initial clinical activity of DuoBody®-PD-L1×4–1BB (GEN1046) in patients with advanced solid tumors

Agonistic 4-1BB monoclonal antibodies were preclinically validated as promising cancer immunotherapies, both as monotherapy and as potentiators of the activity of PD-(L) 1–blocking agents. However, toxicity and a narrow therapeutic window have hampered their clinical development. DuoBodyPD-L1×4-1BB, a first-in-class, bispecific, next-generation checkpoint immunotherapy, was designed to overcome these limitations by activating T cells through conditional 4-1BB costimulation, while simultaneously blocking the PD-L1 axis. We present preliminary data from the ongoing, first-in-human, open-label, phase I/IIa trial of DuoBody-PD-L1×4-1BB in advanced solid tumors (NCT03917381)

Recognizing animal personhood in compassionate conservation

Compassionate conservation is based on the ethical position that actions taken to protect biodiversity should be guided by compassion for all sentient beings. Critics argue that there are 3 core reasons harming animals is acceptable in conservation programs: the primary purpose of conservation is biodiversity protection; conservation is already compassionate to animals; and conservation should prioritize compassion to humans. We used argument analysis to clarify the values and logics underlying the debate around compassionate conservation. We found that objections to compassionate conservation are expressions of human exceptionalism, the view that humans are of a categorically separate and higher moral status than all other species. In contrast, compassionate conservationists believe that conservation should expand its moral community by recognizing all sentient beings as persons. Personhood, in an ethical sense, implies the individual is owed respect and should not be treated merely as a means to other ends. On scientific and ethical grounds, there are good reasons to extend personhood to sentient animals, particularly in conservation. The moral exclusion or subordination of members of other species legitimates the ongoing manipulation and exploitation of the living worlds, the very reason conservation was needed in the first place. Embracing compassion can help dismantle human exceptionalism, recognize nonhuman personhood, and navigate a more expansive moral space

Modeling the effect of roads and other disturbances on wildlife populations in the peri-urban environment to facilitate long-term viability

Roads and traffic exhibit a multitude of impacts on wildlife populations. Most road ecology research seeks to assess the quantity and diversity of fatalities from collisions with vehicles, while studies documenting the impact of roads on the structure and sustainability of wildlife populations adjacent to roads have been lacking. Populations of wildlife existing within the confines of fragmented reserves are particularly susceptible to fatalities on roads, especially those situated within peri-urban and semi-rural matrices. We chose to examine the effects of disturbances, including fatalities on roads, using four case studies from Australia. These studies included a range of fauna, including the long-nosed bandicoot, the koala, and two studies of the swamp wallaby. To explore the impact of the various threats to wildlife living in peri-urban reserves, each case study utilized a population modeling approach. A combination of PVA modeling and sensitivity analysis was used to assess the impact of disturbances on the populations and identify appropriate management options to target disturbances. We discuss the utility of this approach in enabling conservation managers to assess the long-term viability of wildlife in these environments and in establishing management targets for improving viability in populations predicted to decline. In all four cases road fatalities were a major disturbance, but the different landscape characteristics of each reserve and other threat levels altered the relative impact of roads. The findings suggest that the combination of a range of management options, such as road fatality prevention, control of predation, and improvements in immigration and fertility, are often necessary although the exact combination will be location specific. Road management in the peri-urban environment can play a substantial role in ensuring the persistence of isolated populations in protected reserves that are surrounded by, and traversed by, roads. Given the broad geographic scale of roads, their effect on wildlife populations may be best understood from a landscape perspective, taking into account other disturbances that may be influencing population viability. We recommend the integration of PVA, sensitivity analysis, and GIS-based dispersion models as a suitable means for addressing both the temporal and spatial impacts of roads in order to successfully manage wildlife populations

\u27Pest\u27 and Resource: A Legal History of Australia\u27s Kangaroos

This paper presents an investigation into the legal history of Australia’s kangaroos. It aims to provide a detailed analysis of how the law and policy governing the killing of kangaroos has evolved over time in response to changing public perceptions. This history begins with the pre-European period and traces the impact of European colonisation, early growth of the commercial kangaroo industry, and the increased role of science and regulation upon kangaroos. The paper critiques the historical designation of kangaroos as ‘pests’ that need to be ‘managed’ and argues that such an approach is inconsistent with current scientific understanding. As this ‘pest’ status has fallen in importance there has been a shift in regulatory goals from damage mitigation to resource utilisation, although government planning and policy continue to cite damage mitigation alongside objectives to maintain viable populations and a sustainable and commercially viable industry. While the kangaroo industry’s current focus is upon the ‘sustainable use of wildlife’, the history of attitudes towards kangaroos as ‘pests’ is so deeply and widely entrenched that it is impossible for the industry to meet welfare standards. The article concludes that the commercial kangaroo industry does not have any clearly defined policy benefit and should be reassessed to take greater account of the impact it has on ecosystems and kangaroo welfare

'Pest' and resource: a legal history of Australia's kangaroos

This paper presents an investigation into the legal history of Australia’s kangaroos. It aims to provide a detailed analysis of how the law and policy governing the killing of kangaroos has evolved over time in response to changing public perceptions. This history begins with the pre-European period and traces the impact of European colonisation, early growth of the commercial kangaroo industry, and the increased role of science and regulation upon kangaroos. The paper critiques the historical designation of kangaroos as ‘pests’ that need to be ‘managed’ and argues that such an approach is inconsistent with current scientific understanding. As this ‘pest’ status has fallen in importance there has been a shift in regulatory goals from damage mitigation to resource utilisation, although government planning and policy continue to cite damage mitigation alongside objectives to maintain viable populations and a sustainable and commercially viable industry. While the kangaroo industry’s current focus is upon the ‘sustainable use of wildlife’, the history of attitudes towards kangaroos as ‘pests’ is so deeply and widely entrenched that it is impossible for the industry to meet welfare standards. The article concludes that the commercial kangaroo industry does not have any clearly defined policy benefit and should be reassessed to take greater account of the impact it has on ecosystems and kangaroo welfare