A generic activation mode for asymmetric LUMO-lowering catalysis has been developed using the long-established principles of oxy-allyl cation chemistry. Here, the enantioselective conversion of racemic α-tosyloxy ketones to optically enriched α-indolic carbonyls has been accomplished using a new amino alcohol catalyst in the presence of electron-rich indole nucleophiles. Kinetic studies reveal that the rate-determining step in this SN1 pathway is the catalyst-mediated α-tosyloxy ketone deprotonation step to form an enantiodiscriminant oxy-allyl cation prior to the stereodefining nucleophilic addition event.

Immunocytokines hold great potential as anticancer agents, as they use a specific antitumor antibody to deliver an immune-activating cytokine directly to the immunosuppressive tumor microenvironment (TME). We have developed a novel immunocytokine (KD033) composed of a fully human, high-affinity antiprogrammed death-ligand 1 (PD-L1) linked to the sushi-domain of the human IL-15/IL-15 receptor alpha (IL-15/IL-15Rα) complex. A murine PD-L1 cross-reactive KD033 surrogate (srKD033) and a nontargeting antibody (ntKD033) were also developed to investigate mechanism of action in murine tumor models. Efficacy analyses showed a robust antitumor effect of single-dose srKD033 in several diverse syngeneic murine tumor models. In a CT26 murine colon tumor model, single-dose srKD033 produced durable antitumor immunity as evidenced by resistance to subsequent tumor rechallenges. Mice responding to srKD033 treatment showed increased retention of PD-L1/IL-15 in the TME which likely facilitated prolonged IL-15–induced expansion of cytotoxic cells. Importantly, target-based PD-L1/IL-15 delivery via srKD033 was well-tolerated and induced significant antitumor activity in murine carcinoma models that are non- or minimally responsive to IL-15 or anti–PD-L1/PD-1 monotherapy.

Conflicts between groups of animals have individual‐level fitness consequences that can influence the evolution of social behaviour. In the cooperatively breeding greater ani (Crotophaga major), groups occasionally destroy the eggs of their neighbours, causing the attacked group to abandon their nest. Prior research suggested that such conflicts occur when two groups build nests in close proximity, and that established groups tend to evict newcomers. However, inter‐group conflict had never been directly observed. Here, we report the first photographic evidence of egg destruction by greater anis. Twelve artificial nests containing clay eggs were placed in the field with the intent of attracting nest predators. Camera footage revealed that although only two nests were discovered by heterospecific predators (white‐faced capuchins, Cebus capucinus), five nests were visited by resident anis, who in three cases damaged the clay eggs by grasping them with their bills and ejecting them from the nest cup. Nests were discovered between 2 and 96 hr after being placed in the field (mean = 34 hr) and were visited up to 18 times by up to 4 individuals simultaneously. The distance between artificial nests and the nearest known ani territory ranged from 0.13 to 0.28 km (mean = 0.2 km). Resident groups did not subsequently breed at the nest sites that they attacked, consistent with the hypothesis that the main benefit of inter‐group conflict is to reduce competition for local resources rather than to usurp nest sites. This accidental experiment reveals that greater anis closely monitor nesting activity near their territories, which may contribute to the strong “home field advantage” that resident groups hold over intruders.

<p>Heatmap for Changes in Gene Transcription of srKD033/ntKD033 Responder and Non-responder Tumors</p>

<p>Animal Study Designs and Additional Animal Study Data</p>