Medicine, Research & Experimental

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Article Biochemistry & Molecular Biology

Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non-small-cell lung cancer

Lisa Derosa, Bertrand Routy, Andrew Maltez Thomas, Valerio Iebba, Gerard Zalcman, Sylvie Friard, Julien Mazieres, Clarisse Audigier-Valette, Denis Moro-Sibilot, Francois Goldwasser, Carolina Alves Costa Silva, Safae Terrisse, Melodie Bonvalet, Arnaud Scherpereel, Herve Pegliasco, Corentin Richard, Francois Ghiringhelli, Arielle Elkrief, Antoine Desilets, Felix Blanc-Durand, Fabio Cumbo, Aitor Blanco, Romain Boidot, Sandy Chevrier, Romain Daillere, Guido Kroemer, Laurie Alla, Nicolas Pons, Emmanuelle Le Chatelier, Nathalie Galleron, Hugo Roume, Agathe Dubuisson, Nicole Bouchard, Meriem Messaoudene, Damien Drubay, Eric Deutsch, Fabrice Barlesi, David Planchard, Nicola Segata, Stephanie Martinez, Laurence Zitvogel, Jean-Charles Soria, Benjamin Besse

Summary: In addition to PD-L1 expression, biomarkers for predicting the response to immune checkpoint inhibitors (ICIs) in non-small-cell lung cancer (NSCLC) are needed. This study found that fecal Akkermansia muciniphila (Akk) was associated with clinical benefit of ICI treatment in NSCLC patients, independent of PD-L1 expression and other factors. The relative abundance of Akk in the gut microbiome may serve as a potential biomarker for patient stratification.

NATURE MEDICINE (2022)

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Article Biochemistry & Molecular Biology

Low neutralization of SARS-CoV-2 Omicron BA.2.75.2, BQ.1.1 and XBB.1 by parental mRNA vaccine or a BA.5 bivalent booster

Chaitanya Kurhade, Jing Zou, Hongjie Xia, Mingru Liu, Hope C. Chang, Ping Ren, Xuping Xie, Pei-Yong Shi

Summary: This study reported on the neutralizing activities of a BA.5 bivalent booster against SARS-CoV-2 Omicron sublineages. The results showed that the BA.5 bivalent booster had good neutralizing efficacy against BA.4/5 but weaker efficacy against BA.2.75.2, BQ.1.1, and XBB.1. Previous infection significantly enhanced the strength and breadth of neutralization induced by the BA.5 bivalent booster. These data support a vaccine update strategy that matches newly emerged SARS-CoV-2 variants.

NATURE MEDICINE (2023)

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Article Biochemistry & Molecular Biology

Infectious viral load in unvaccinated and vaccinated individuals infected with ancestral, Delta or Omicron SARS-CoV-2

Olha Puhach, Kenneth Adea, Nicolas Hulo, Pascale Sattonnet, Camille Genecand, Anne Iten, Frederique Jacquerioz, Laurent Kaiser, Pauline Vetter, Isabella Eckerle, Benjamin Meyer

Summary: The infectious viral load of SARS-CoV-2 Omicron BA.1 is lower than that of Delta in breakthrough infections of vaccinated individuals. Vaccines may lower transmission risk and have a public health benefit.

NATURE MEDICINE (2022)

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Article Biochemistry & Molecular Biology

Three exposures to the spike protein of SARS-CoV-2 by either infection or vaccination elicit superior neutralizing immunity to all variants of concern

Paul R. Wratil, Marcel Stern, Alina Priller, Annika Willmann, Giovanni Almanzar, Emanuel Vogel, Martin Feuerherd, Cho-Chin Cheng, Sarah Yazici, Catharina Christa, Samuel Jeske, Gaia Lupoli, Tim Vogt, Manuel Albanese, Ernesto Mejias-Perez, Stefan Bauernfried, Natalia Graf, Hrvoje Mijocevic, Martin Vu, Kathrin Tinnefeld, Jochen Wettengel, Dieter Hoffmann, Maximilian Muenchhoff, Christopher Daechert, Helga Mairhofer, Stefan Krebs, Volker Fingerle, Alexander Graf, Philipp Steininger, Helmut Blum, Veit Hornung, Bernhard Liebl, Klaus Ueberla, Martina Prelog, Percy Knolle, Oliver T. Keppler, Ulrike Protzer

Summary: This study reports on the dynamics of neutralizing antibodies in individuals convalescing from coronavirus disease 2019 or who are vaccine-naive and subsequently vaccinated. The findings suggest that infection-plus-vaccination-induced hybrid immunity or triple immunization can induce high-quality antibodies with superior neutralization capacity against variants of concern, including omicron.

NATURE MEDICINE (2022)

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Review Biochemistry & Molecular Biology

A guide to immunotherapy for COVID-19

Frank L. van de Veerdonk, Evangelos Giamarellos-Bourboulis, Peter Pickkers, Lennie Derde, Helen Leavis, Reinout van Crevel, Job J. Engel, W. Joost Wiersinga, Alexander P. J. Vlaar, Manu Shankar-Hari, Tom van der Poll, Marc Bonten, Derek C. Angus, Jos W. M. van der Meer, Mihai G. Netea

Summary: This review provides an overview of the evidence for immunotherapy strategies in COVID-19 patients, aiming to support clinical decision-making. Immune dysregulation plays a crucial role in the pathophysiology of COVID-19. Immune-based therapies, such as steroids or anti-cytokine therapies, have shown remarkable successes in treating COVID-19 patients. However, the complexity of disease phenotypes, patient heterogeneity, and variable quality of evidence from immunotherapy studies pose challenges to clinical decision-making. This review summarizes the evidence generated by major clinical trials of host-directed therapy and proposes an algorithm for guiding the use of immunotherapy strategies in the clinic, which can not only guide treatment decisions but also inform future trials investigating immunotherapy in severe infections.

NATURE MEDICINE (2022)

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Article Cell Biology

A phase 2a clinical trial of molnupiravir in patients with COVID-19 shows accelerated SARS-CoV-2 RNA clearance and elimination of infectious virus

William A. Fischer, Joseph J. Eron, Wayne Holman, Myron S. Cohen, Lei Fang, Laura J. Szewczyk, Timothy P. Sheahan, Ralph Baric, Katie R. Mollan, Cameron R. Wolfe, Elizabeth R. Duke, Masoud M. Azizad, Katyna Borroto-Esoda, David A. Wohl, Robert W. Coombs, Amy James Loftis, Paul Alabanza, Felicia Lipansky, Wendy P. Painter

Summary: In a clinical trial, the safety, tolerability, and antiviral efficacy of molnupiravir were evaluated in unvaccinated individuals with confirmed SARS-CoV-2 infection. The study found that participants receiving high-dose molnupiravir had a shorter time to viral RNA clearance and a lower detection rate of infectious virus. Molnupiravir was well tolerated across all doses.

SCIENCE TRANSLATIONAL MEDICINE (2022)

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Article Biochemistry & Molecular Biology

Clinical outcomes associated with SARS-CoV-2 Omicron (B.1.1.529) variant and BA.1/BA.1.1 or BA.2 subvariant infection in Southern California

Joseph A. Lewnard, Vennis X. Hong, Manish M. Patel, Rebecca Kahn, Marc Lipsitch, Sara Y. Tartof

Summary: Comparison of outcomes of SARS-CoV-2 Delta and Omicron infections reveals reduced severity of Omicron infections, especially in unvaccinated individuals. There is no differential risk of severe outcomes between subvariants BA.1 and BA.2. Continual assessment of clinical outcomes associated with SARS-CoV-2 variants is crucial for medical interventions and healthcare resource management.

NATURE MEDICINE (2022)

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Article Biochemistry & Molecular Biology

Nivolumab plus ipilimumab with or without live bacterial supplementation in metastatic renal cell carcinoma: a randomized phase 1 trial

Nazli Dizman, Luis Meza, Paulo Bergerot, Marice Alcantara, Tanya Dorff, Yung Lyou, Paul Frankel, Yujie Cui, Valerie Mira, Marian Llamas, Joann Hsu, Zeynep Zengin, Nicholas Salgia, Sabrina Salgia, Jasnoor Malhotra, Neal Chawla, Alex Chehrazi-Raffle, Ramya Muddasani, John Gillece, Lauren Reining, Jeff Trent, Motomichi Takahashi, Kentaro Oka, Seiya Higashi, Marcin Kortylewski, Sarah K. Highlander, Sumanta K. Pal

Summary: Adding a live bacterial product to an immunotherapy combination can enhance the clinical outcome in patients with metastatic renal cell carcinoma, showing longer progression-free survival and higher response rate.

NATURE MEDICINE (2022)

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Article Biochemistry & Molecular Biology

Claudin18.2-specific CAR T cells in gastrointestinal cancers: phase 1 trial interim results

Changsong Qi, Jifang Gong, Jian Li, Dan Liu, Yanru Qin, Sai Ge, Miao Zhang, Zhi Peng, Jun Zhou, Yanshuo Cao, Xiaotian Zhang, Zhihao Lu, Ming Lu, Jiajia Yuan, Zhenghang Wang, Yakun Wang, Xiaohui Peng, Huiping Gao, Zhen Liu, Huamao Wang, Daijing Yuan, Jun Xiao, Hong Ma, Wei Wang, Zonghai Li, Lin Shen

Summary: The interim analysis results of a phase 1 clinical trial show that CLDN18.2-targeted CAR T cell therapy has promising efficacy and an acceptable safety profile in previously treated, CLDN18.2-positive digestive system cancer patients. Particularly, it shows significant efficacy in patients with gastric cancer.

NATURE MEDICINE (2022)

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Review Biochemistry & Molecular Biology

Unexplained post-acute infection syndromesUnexplained post-acute infection syndromes

Jan Choutka, Viraj Jansari, Mady Hornig, Akiko Iwasaki

Summary: Unexplained post-acute infection syndromes (PAISs) represent a group of chronic illnesses with overlapping clinical features with chronic fatigue syndrome (ME/CFS). This review summarizes the current knowledge of PAISs and discusses the need for basic biomedical research into the underlying mechanisms of these enigmatic chronic diseases, including the post-acute sequelae of SARS-CoV-2 infection (PASC).

NATURE MEDICINE (2022)

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Article Biochemistry & Molecular Biology

Modeling transmission of SARS-CoV-2 Omicron in China

Jun Cai, Xiaowei Deng, Juan Yang, Kaiyuan Sun, Hengcong Liu, Zhiyuan Chen, Cheng Peng, Xinhua Chen, Qianhui Wu, Junyi Zou, Ruijia Sun, Wen Zheng, Zeyao Zhao, Wanying Lu, Yuxia Liang, Xiaoyu Zhou, Marco Ajelli, Hongjie Yu

Summary: China is considering whether to continue the zero COVID-19 strategy and discussing how to minimize the impact of a nationwide outbreak on the healthcare system. A modeling study suggests that the current vaccine coverage in China is insufficient to prevent overwhelming the healthcare system, and an untreated Omicron wave could result in up to 1.55 million deaths nationwide.

NATURE MEDICINE (2022)

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Article Biochemistry & Molecular Biology

PSMA-targeting TGFβ-insensitive armored CAR T cells in metastatic castration-resistant prostate cancer: a phase 1 trial

Vivek Narayan, Julie S. Barber-Rotenberg, In-Young Jung, Simon F. Lacey, Andrew J. Rech, Megan M. Davis, Wei-Ting Hwang, Priti Lal, Erica L. Carpenter, Shannon L. Maude, Gabriela Plesa, Neha Vapiwala, Anne Chew, Michael Moniak, Ronnie A. Sebro, Michael D. Farwell, Amy Marshall, Joan Gilmore, Lester Lledo, Karen Dengel, Sarah E. Church, Tyler D. Hether, Jun Xu, Mercy Gohil, Thomas H. Buckingham, Stephanie S. Yee, Vanessa E. Gonzalez, Irina Kulikovskaya, Fang Chen, Lifeng Tian, Kyle Tien, Whitney Gladney, Christopher L. Nobles, Hayley E. Raymond, Elizabeth O. Hexner, Donald L. Siegel, Frederic D. Bushman, Carl H. June, Joseph A. Fraietta, Naomi B. Haas

Summary: CAR T cells show promising efficacy in hematologic malignancies, but face challenges in solid tumors due to the immunosuppressive tumor microenvironment. This study reports results from a phase 1 trial using engineered CAR T cells resistant to TGF-beta signaling in castration-resistant prostate cancer patients, showing both efficacy and dose-dependent toxicity. Future studies should explore multipronged approaches to improve outcomes in this setting.

NATURE MEDICINE (2022)

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Article Biochemistry & Molecular Biology

SARS-CoV-2 infection and COVID-19 vaccination rates in pregnant women in Scotland

Sarah J. Stock, Jade Carruthers, Clara Calvert, Cheryl Denny, Jack Donaghy, Anna Goulding, Lisa E. M. Hopcroft, Leanne Hopkins, Terry McLaughlin, Jiafeng Pan, Ting Shi, Bob Taylor, Utkarsh Agrawal, Bonnie Auyeung, Srinivasa Vittal Katikireddi, Colin McCowan, Josie Murray, Colin R. Simpson, Chris Robertson, Eleftheria Vasileiou, Aziz Sheikh, Rachael Wood

Summary: Population-level data on COVID-19 vaccine uptake in pregnancy and SARS-CoV-2 infection outcomes are lacking. However, this study reveals low levels of vaccination uptake by pregnant women compared to women in the general population and that not being vaccinated is associated with increased risk of severe complications of COVID-19 in pregnancy, including perinatal mortality.

NATURE MEDICINE (2022)

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Article Instruments & Instrumentation

Enhancement strategies for transdermal drug delivery systems: current trends and applications

Delly Ramadon, Maeliosa T. C. McCrudden, Aaron J. Courtenay, Ryan F. Donnelly

Summary: Transdermal drug delivery systems have become an intriguing research topic in pharmaceutical technology area and one of the most frequently developed pharmaceutical products in global market. This article reviews the current trends, and future applications of transdermal technologies, with specific focus on providing a comprehensive understanding of transdermal drug delivery systems and enhancement strategies. The use of microneedle technology has shown promising results in improving transdermal delivery systems, with opportunities for intradermal delivery of drugs/biotherapeutics and therapeutic drug monitoring.

DRUG DELIVERY AND TRANSLATIONAL RESEARCH (2022)

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Review Medicine, Research & Experimental

Platinum-based drugs for cancer therapy and anti-tumor strategies

Chunyu Zhang, Chao Xu, Xueyun Gao, Qingqiang Yao

Summary: This article discusses the application and development of platinum-based drugs in cancer treatment, particularly the targeted modification of platinum nanoclusters. The new platinum drugs provide a promising prospect for improving anti-cancer treatments.

THERANOSTICS (2022)

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Article Immunology

Large-Scale Study of Antibody Titer Decay following BNT162b2 mRNA Vaccine or SARS-CoV-2 Infection

Ariel Israel, Yotam Shenhar, Ilan Green, Eugene Merzon, Avivit Golan-Cohen, Alejandro A. Schaeffer, Eytan Ruppin, Shlomo Vinker, Eli Magen

Summary: This study demonstrates that individuals who received the Pfizer-BioNTech mRNA vaccine have higher initial levels of antibodies compared to patients who had been infected with the SARS-CoV-2 virus, but experience a much faster exponential decrease in antibody levels.

VACCINES (2022)

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Article Biochemistry & Molecular Biology

Tisagenlecleucel in adult relapsed or refractory follicular lymphoma: the phase 2 ELARA trial

Nathan Hale Fowler, Michael Dickinson, Martin Dreyling, Joaquin Martinez-Lopez, Arne Kolstad, Jason Butler, Monalisa Ghosh, Leslie Popplewell, Julio C. Chavez, Emmanuel Bachy, Koji Kato, Hideo Harigae, Marie Jose Kersten, Charalambos Andreadis, Peter A. Riedell, P. Joy Ho, Jose Antonio Perez-Simon, Andy Chen, Loretta J. Nastoupil, Bastian von Tresckow, Andres Jose Maria Ferreri, Takanori Teshima, Piers E. M. Patten, Joseph P. McGuirk, Andreas L. Petzer, Fritz Offner, Andreas Viardot, Pier Luigi Zinzani, Ram Malladi, Aiesha Zia, Rakesh Awasthi, Aisha Masood, Oezlem Anak, Stephen J. Schuster, Catherine Thieblemont

Summary: Tisagenlecleucel, an autologous anti-CD19 CAR-T cell therapy, demonstrated a high complete response rate of 69.1% and overall response rate of 86.2% in adults with relapsed or refractory follicular lymphoma. Adverse events post-treatment primarily included cytokine release syndrome and neurological events, with no treatment-related deaths reported.

NATURE MEDICINE (2022)

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Article Biochemistry & Molecular Biology

Molecular correlates of clinical response and resistance to atezolizumab in combination with bevacizumab in advanced hepatocellular carcinoma

Andrew X. Zhu, Alexander R. Abbas, Marina Ruiz de Galarreta, Yinghui Guan, Shan Lu, Hartmut Koeppen, Wenjun Zhang, Chih-Hung Hsu, Aiwu Ruth He, Baek-Yeol Ryoo, Thomas Yau, Ahmed O. Kaseb, Adam M. Burgoyne, Farshid Dayyani, Jessica Spahn, Wendy Verret, Richard S. Finn, Han Chong Toh, Amaia Lujambio, Yulei Wang

Summary: This study analyzed tumor samples from patients with hepatocellular carcinoma and found that combination therapy with atezolizumab and bevacizumab was effective in treating this type of cancer. Patients with high expression of VEGF Receptor 2, regulatory T cells, and myeloid inflammation signatures showed better outcomes with the combination therapy compared to atezolizumab alone. These findings provide insights into baseline immune and genetic features that can identify patients who will benefit from the combination therapy of atezolizumab and bevacizumab in advanced hepatocellular carcinoma.

NATURE MEDICINE (2022)

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Article Biochemistry & Molecular Biology

Activity-dependent spinal cord neuromodulation rapidly restores trunk and leg motor functions after complete paralysis

Andreas Rowald, Salif Komi, Robin Demesmaeker, Edeny Baaklini, Sergio Daniel Hernandez-Charpak, Edoardo Paoles, Hazael Montanaro, Antonino Cassara, Fabio Becce, Bryn Lloyd, Taylor Newton, Jimmy Ravier, Nawa Kinany, Marina D'Ercole, Aurelie Paley, Nicolas Hankov, Camille Varescon, Laura McCracken, Molywan Vat, Miroslav Caban, Anne Watrin, Charlotte Jacquet, Lea Bole-Feysot, Cathal Harte, Henri Lorach, Andrea Galvez, Manon Tschopp, Natacha Herrmann, Moira Wacker, Lionel Geernaert, Isabelle Fodor, Valentin Radevich, Katrien van den Keybus, Gregoire Eberle, Etienne Pralong, Maxime Roulet, Jean-Baptiste Ledoux, Eleonora Fornari, Stefano Mandija, Loan Mattera, Roberto Martuzzi, Bruno Nazarian, Stefan Benkler, Simone Callegari, Nathan Greiner, Benjamin Fuhrer, Martijn Froeling, Nik Buse, Tim Denison, Rik Buschman, Christian Wende, Damien Ganty, Jurriaan Bakker, Vincent Delattre, Hendrik Lambert, Karen Minassian, Cornelis A. T. van den Berg, Anne Kavounoudias, Silvestro Micera, Dimitri van de Ville, Quentin Barraud, Erkan Kurt, Niels Kuster, Esra Neufeld, Marco Capogrosso, Leonie Asboth, Fabien B. Wagner, Jocelyne Bloch, Gregoire Courtine

Summary: Epidural electrical stimulation (EES) targeting the dorsal roots of lumbosacral segments restores walking ability in people with spinal cord injury. Using a computational framework and software, activity-specific stimulation programs allowed patients to perform various motor activities within a day. Neurorehabilitation significantly improved patients' everyday mobility.

NATURE MEDICINE (2022)

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Article Immunology

Trust in government, intention to vaccinate and COVID-19 vaccine hesitancy: A comparative survey of five large cities in the United States, United Kingdom, and Australia

Mallory Trent, Holly Seale, Abrar Ahmad Chughtai, Daniel Salmon, C. Raina MacIntyre

Summary: There is widespread hesitancy towards COVID-19 vaccines in the United States, United Kingdom, and Australia. Age is the only sociodemographic characteristic that predicted willingness to receive a COVID-19 vaccine in all five cities. Confidence in the current government was associated with willingness to vaccinate in Sydney and Melbourne, but was associated with lower willingness in NYC and Phoenix.

VACCINE (2022)

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