@article {68957,
	title = {Hydrophobic interactions dominate the recognition of a KRAS G12V neoantigen.},
	journal = {Nature Communications},
	volume = {14},
	year = {2023},
	month = {2023 Aug 21},
	pages = {5063},
	abstract = {<p>Specificity remains a major challenge to current therapeutic strategies for cancer. Mutation associated neoantigens (MANAs) are products of genetic alterations, making them highly specific therapeutic targets. MANAs are HLA-presented (pHLA) peptides derived from intracellular mutant proteins that are otherwise inaccessible to antibody-based therapeutics. Here, we describe the cryo-EM structure of an antibody-MANA pHLA complex. Specifically, we determine a TCR mimic (TCRm) antibody bound to its MANA target, the KRAS peptide presented by HLA-A*03:01. Hydrophobic residues appear to account for the specificity of the mutant G12V residue. We also determine the structure of the wild-type G12 peptide bound to HLA-A*03:01, using X-ray crystallography. Based on these structures, we perform screens to validate the key residues required for peptide specificity. These experiments led us to a model for discrimination between the mutant and the wild-type peptides presented on HLA-A*03:01 based exclusively on hydrophobic interactions.</p>
},
	keywords = {Antibodies, HLA-A Antigens, Hydrophobic and Hydrophilic Interactions, Proto-Oncogene Proteins p21(ras), Recognition, Psychology},
	issn = {2041-1723},
	doi = {10.1038/s41467-023-40821-w},
	author = {Wright, Katharine M and DiNapoli, Sarah R and Miller, Michelle S and Aitana Azurmendi, P and Zhao, Xiaowei and Yu, Zhiheng and Chakrabarti, Mayukh and Shi, WuXian and Douglass, Jacqueline and Hwang, Michael S and Hsiue, Emily Han-Chung and Mog, Brian J and Pearlman, Alexander H and Paul, Suman and Konig, Maximilian F and Pardoll, Drew M and Bettegowda, Chetan and Papadopoulos, Nickolas and Kinzler, Kenneth W and Vogelstein, Bert and Zhou, Shibin and Gabelli, Sandra B}
}
@article {67314,
	title = {Alpha-1 adrenergic receptor antagonists to prevent hyperinflammation and death from lower respiratory tract infection.},
	journal = {eLife},
	volume = {10},
	year = {2021},
	month = {2021 Jun 11},
	abstract = {<p>In severe viral pneumonia, including Coronavirus disease 2019 (COVID-19), the viral replication phase is often followed by hyperinflammation, which can lead to acute respiratory distress syndrome, multi-organ failure, and death. We previously demonstrated that alpha-1 adrenergic receptor (⍺-AR) antagonists can prevent hyperinflammation and death in mice. Here, we conducted retrospective analyses in two cohorts of patients with acute respiratory distress (ARD, n = 18,547) and three cohorts with pneumonia (n = 400,907). Federated across two ARD cohorts, we find that patients exposed to ⍺-AR antagonists, as compared to unexposed patients, had a 34\% relative risk reduction for mechanical ventilation and death (OR = 0.70, p = 0.021). We replicated these methods on three pneumonia cohorts, all with similar effects on both outcomes. All results were robust to sensitivity analyses. These results highlight the urgent need for prospective trials testing whether prophylactic use of ⍺-AR antagonists ameliorates lower respiratory tract infection-associated hyperinflammation and death, as observed in COVID-19.</p>
},
	issn = {2050-084X},
	doi = {10.7554/eLife.61700},
	author = {Koenecke, Allison and Powell, Michael and Xiong, Ruoxuan and Shen, Zhu and Fischer, Nicole and Huq, Sakibul and Khalafallah, Adham M and Trevisan, Marco and Sparen, P{\"a}r and Carrero, Juan J and Nishimura, Akihiko and Caffo, Brian and Stuart, Elizabeth A and Bai, Renyuan and Staedtke, Verena and Thomas, David L and Papadopoulos, Nickolas and Kinzler, Ken W and Vogelstein, Bert and Zhou, Shibin and Bettegowda, Chetan and Konig, Maximilian F and Mensh, Brett D and Vogelstein, Joshua T and Athey, Susan}
}
@article {65721,
	title = {Preventing cytokine storm syndrome in COVID-19 using α-1 adrenergic receptor antagonists.},
	journal = {The Journal of Clinical Investigatio},
	volume = {130},
	year = {2020},
	month = {2020 Jul 01},
	pages = {3345-47},
	keywords = {Adrenergic alpha-1 Receptor Antagonists, Clinical Trials as Topic, Coronavirus Infections, Cytokine Release Syndrome, Humans, Pandemics, Pneumonia, Viral},
	issn = {1558-8238},
	doi = {10.1172/JCI139642},
	author = {Konig, Maximilian F and Powell, Mike and Staedtke, Verena and Bai, Ren-Yuan and Thomas, David L and Fischer, Nicole and Huq, Sakibul and Khalafallah, Adham M and Koenecke, Allison and Xiong, Ruoxuan and Mensh, Brett and Papadopoulos, Nickolas and Kinzler, Kenneth W and Vogelstein, Bert and Vogelstein, Joshua T and Athey, Susan and Zhou, Shibin and Bettegowda, Chetan}
}
