Article
Medicine, Research & Experimental
Yajun Zhang, Pei Wang, Tengjiao Wang, Yuan Fang, Yongmei Ding, Qijun Qian
Summary: This study demonstrates that CAR-T cells engineered to secrete anti-CD40 antibodies using a nonviral vector system have enhanced antitumor efficacy against solid tumors, showing increased cytokine secretion, higher proportion of central memory T cells, and improved cytotoxicity. In a human ovarian cancer xenograft model, these anti-CD40-secreting CAR-T cells showed enhanced antitumor activity, suggesting their potential as a clinical strategy to improve CAR-T cell therapy efficacy.
JOURNAL OF TRANSLATIONAL MEDICINE
(2021)
Article
Multidisciplinary Sciences
Jake Burton, Jesus A. Siller-Farfan, Johannes Pettmann, Benjamin Salzer, Mikhail Kutuzov, P. Anton van der Merwe, Omer Dushek
Summary: Chimeric antigen receptors (CARs) have lower sensitivity to antigens presented on antigen-presenting cells (APCs) compared to T cell receptors (TCR), but nearly identical sensitivity to purified protein antigens. Engaging CD2 or LFA-1 can significantly improve TCR sensitivity, but has minimal effect on CAR sensitivity. Fusion of CAR variable domains to the TCR CD3 epsilon subunit (TRuC) or exchanging TCR alpha beta variable domains for those of the CAR (STAR or HIT) can partially or fully restore antigen sensitivity, respectively, by enhancing their ability to exploit CD2 and LFA-1.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Oncology
Jonathan E. Brammer, Zachary Braunstein, Aashish Katapadi, Kyle Porter, Michael Biersmith, Avirup Guha, Sumithira Vasu, Vedat O. Yildiz, Sakima A. Smith, Benjamin Buck, Devin Haddad, Richard Gumina, Basem M. William, Sam Penza, Ayman Saad, Nathan Denlinger, Ajay Vallakati, Ragavendra Baliga, Raymond Benza, Philip Binkley, Lai Wei, Mason Mocarski, Steven M. Devine, Samantha Jaglowski, Daniel Addison
Summary: Moderate toxicity such as grade 2 CRS after CAR-T infusion in adult lymphoma patients may be associated with favorable clinical outcomes. Further studies are needed to confirm these findings.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2021)
Article
Oncology
Konstantinos Lontos, Yiyang Wang, Supriya K. Joshi, Andrew T. Frisch, McLane J. Watson, Alok Kumar, Ashley Menk, Yupeng Wang, Rachel Cumberland, Jason Lohmueller, Esteban Carrizosa, Benjamin Boyerinas, Greg M. Delgoffe
Summary: This study demonstrates that an engineered version of the inhibitory transcription factor PGC-1 alpha can metabolically reprogram human CAR-T cells, resulting in improved in vivo efficacy for the treatment of solid tumors. In contrast, a truncated version of PGC-1 alpha, NT-PGC-1 alpha, did not improve the in vivo outcomes.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2023)
Article
Immunology
Georgia F. Papadaki, Omar Ani, Tyler J. Florio, Michael C. Young, Julia N. Danon, Yi Sun, Devin Dersh, Nikolaos G. Sgourakis
Summary: Major Histocompatibility Complex class I (MHC-I) molecules present self, viral or aberrant epitopic peptides to T cell receptors (TCRs) through interactions with complementarity-determining regions and MHC-I heavy chain 'framework' residues. In this study, using structural data from peptide:MHC-I and pMHC:TCR structures, the researchers identified important residues for peptide and/or TCR binding and proposed a fixed-backbone computational design approach for engineering synthetic molecules with desired properties. Experimental results showed that chimeric molecules bridging divergent HLA alleles can bind selected peptide antigens, highlighting the potential of these synthetic HLA molecules as screening probes for peptide-centric interactions with TCRs and other therapeutic modalities.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Oncology
Sophia Stock, Mohamed-Reda Benmebarek, Anna-Kristina Kluever, Diana Darowski, Christian Jost, Kay-Gunnar Stubenrauch, Joerg Benz, Anne Freimoser-Grundschober, Ekkehard Moessner, Pablo Umana, Marion Subklewe, Stefan Endres, Christian Klein, Sebastian Kobold
Summary: This study developed a P329G-directed CAR T cell that can selectively bind with specific mutated antibodies, demonstrating significant in vitro and in vivo effector functions in different types of solid tumor models. This opens up possibilities for further clinical translation.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Article
Immunology
Ronit Rosenfeld, Ron Alcalay, Anat Zvi, Alon Ben-David, Tal Noy-Porat, Theodor Chitlaru, Eyal Epstein, Ofir Israeli, Shirley Lazar, Noa Caspi, Ada Barnea, Eyal Dor, Inbar Chomsky, Shani Pitel, Efi Makdasi, Ran Zichel, Ohad Mazor
Summary: This study documents the development of novel tools for equine antibody engineering and demonstrates their therapeutic potential in animal models. The findings have significant implications for the isolation and engineering of therapeutic equine antibodies.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Oncology
P. Connor Johnson, Caron Jacobson, Alisha Yi, Mahmoud R. Gaballa, Nora Horick, Dustin J. Rabideau, Kevin Lindell, Gabriel D. DePinho, Areej R. El-Jawahri, Matthew J. Frigault
Summary: A retrospective analysis of 235 patients receiving CAR T-cell therapy found that bridging therapy use was not associated with differences in overall response, complete response rate, or progression-free survival, but was associated with worse overall survival. Additional poor prognostic factors may contribute to this association, highlighting the need for innovative bridging therapy regimens for these patients.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Review
Cell & Tissue Engineering
Ali Keshavarz, Ali Salehi, Setareh Khosravi, Yasaman Shariati, Navid Nasrabadi, Mohammad Saeed Kahrizi, Sairan Maghsoodi, Amirhossein Mardi, Ramyar Azizi, Samira Jamali, Farnoush Fotovat
Summary: Advancements in adoptive cell therapy have brought forth new therapeutic strategies like CAR T-cells, showing promise in hematological malignancies. However, obstacles remain in using CAR T-cell therapy for both solid tumors and hematological malignancies. CAR-NK and CAR-M cell therapies have emerged as solutions to these challenges. Trials are ongoing in different human malignancies worldwide to improve CAR immune cell therapy.
STEM CELL RESEARCH & THERAPY
(2022)
Article
Immunology
Thai Leong Yap, Shin Yee Hong, Jun Hui Soh, Lekha Ravichandraprabhu, Vanessa W. X. Lim, Hsi-Min Chan, Tommy Z. X. Ong, Ying Ping Chua, Shi En Koh, Huajing Wang, Yee Sin Leo, Jackie Y. Ying, William Sun
Summary: Dengue virus and Zika virus, both transmitted by Aedes mosquitoes, require accurate diagnostic tests for patient management and disease control. Serological tests, particularly using engineered ZIKV NS1 antibodies, can help increase sensitivity in detecting early infections.
EMERGING INFECTIOUS DISEASES
(2021)
Article
Cell Biology
Zhenyu Dai, Xuelian Hu, Xiangyin Jia, Jianwei Liu, Yongkun Yang, Panpan Niu, Guang Hu, Taochao Tan, Jianfeng Zhou
Summary: Through an optimized screening strategy, two human anti-CD19 scFv candidates were discovered in this study, showing excellent cytotoxicity in CAR-T cells and bispecific antibodies. Clone 78-BBz CAR-T cells demonstrated similar in vivo antitumor activity to FMC63-BBz CAR-T cells, indicating excellent efficacy and safety profile as a potential candidate for clinical development.
JOURNAL OF CELLULAR PHYSIOLOGY
(2021)
Review
Immunology
Kajal Chaudhry, Ehsan Dowlati, Catherine M. Bollard
Summary: CAR NK cell therapies show promise as an 'off-the-shelf' cancer cell therapy. It is hoped that enhanced understanding of their immunobiology and molecular mechanisms of action will improve their in vivo potency.
EXPERT REVIEW OF CLINICAL IMMUNOLOGY
(2021)
Article
Oncology
Liyuan Wu, Fei Liu, Le Yin, Fangming Wang, Hui Shi, Qinxin Zhao, Feiya Yang, Dong Chen, Xiying Dong, Yuchun Gu, Nianzeng Xing
Summary: A novel CAR-NK cell with a clinically significant tumoricidal effect on castration-resistant prostate cancer (CRPC) was designed and verified to have anti-tumor effects in vitro and in vivo.
CANCER COMMUNICATIONS
(2022)
Review
Biochemistry & Molecular Biology
Katarzyna M. Terlikowska, Bozena Dobrzycka, Slawomir J. Terlikowski
Summary: The advancement in our understanding of tumor biology has led to the development of targeted molecular therapies, such as CARs, which show potential in treating ovarian cancer. identification. CARs targeting overexpressed molecules in tumor cells causes high toxicity and reduces tumor burden with minimal side effects, inhibiting disease progression.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Oncology
M. Lia Palomba, David Qualls, Sebastien Monette, Shenon Sethi, Ahmet Dogan, Mikhail Roshal, Brigitte Senechal, Xiuyan Wang, Isabelle Riviere, Michel Sadelain, Renier J. Brentjens, Jae H. Park, Eric L. Smith
Summary: This report summarizes the preclinical and clinical activity of CD19-directed CAR T therapy in WM, demonstrating early tolerability and efficacy in patients with heavily pretreated and relapsed or refractory WM, and representing a possible treatment option.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Review
Oncology
William R. Strohl
Article
Biotechnology & Applied Microbiology
Kristina Carlson, Steven C. Pomerantz, Omid Vafa, Michael Naso, William Strohl, Richard E. Mains, Betty A. Eipper
Article
Biotechnology & Applied Microbiology
Kristina R. Carlson, Steven C. Pomerantz, Jiali Li, Omid Vafa, Michael Naso, William Strohl, Richard E. Mains, Betty A. Eipper
Article
Oncology
Ningyan Zhang, Hui Deng, Xuejun Fan, Anneliese Gonzalez, Songlin Zhang, Randall J. Brezski, Byung-Kwon Choi, Michael Rycyzyn, William Strohl, Robert Jordan, Zhiqiang An
CLINICAL CANCER RESEARCH
(2015)
Article
Medicine, Research & Experimental
Michelle Kinder, Allison R. Greenplate, William R. Strohl, Robert E. Jordan, Randall J. Brezski
Review
Pharmacology & Pharmacy
William E. Sause, Peter T. Buckley, William R. Strohl, A. Simon Lynch, Victor J. Torres
TRENDS IN PHARMACOLOGICAL SCIENCES
(2016)
Editorial Material
Biotechnology & Applied Microbiology
T. Shantha Raju, William R. Strohl
EXPERT OPINION ON BIOLOGICAL THERAPY
(2013)
Article
Biochemistry & Molecular Biology
Michelle Kinder, Allison R. Greenplate, Katharine D. Grugan, Keri L. Soring, Katharine A. Heeringa, Stephen G. McCarthy, Gregory Bannish, Meredith Perpetua, Frank Lynch, Robert E. Jordan, William R. Strohl, Randall J. Brezski
JOURNAL OF BIOLOGICAL CHEMISTRY
(2013)
Article
Biochemical Research Methods
Omid Vafa, Gary L. Gilliland, Randall J. Brezski, Brandy Strake, Teresa Wilkinson, Eilyn R. Lacy, Bernard Scallon, Alexey Teplyakov, Thomas J. Malia, William R. Strohl
Article
Oncology
Xuejun Fan, Randall J. Brezski, Hui Deng, Pooja M. Dhupkar, Yun Shi, Anneliese Gonzalez, Songlin Zhang, Michael Rycyzyn, William R. Strohl, Robert E. Jordan, Ningyan Zhang, Zhiqiang An
MOLECULAR CANCER THERAPEUTICS
(2015)
Article
Cell Biology
Rita Chan, Peter T. Buckley, Aidan O'Malley, William E. Sause, Francis Alonzo, Ashira Lubkin, Kristina M. Boguslawski, Angela Payne, Jeffrey Fernandez, William R. Strohl, Brian Whitaker, Anthony Simon Lynch, Victor J. Torres
SCIENCE TRANSLATIONAL MEDICINE
(2019)
Article
Oncology
William R. Strohl, Zhiqiang Ku, Zhiqiang An, Stephen F. Carroll, Bruce A. Keyt, Lila M. Strohl
Summary: The COVID-19 pandemic has lasted for nearly two years and has caused a significant number of infections and deaths worldwide. The discovery of SARS-CoV-2 led to the immediate development of vaccines and therapeutic antibodies by various companies and institutes. Multiple antibodies have been generated and tested, and they target different regions of the virus to prevent its binding to human cells. However, the emergence of new variants has posed challenges to the effectiveness of these antibodies. This review provides an overview of the development and application of antibodies against SARS-CoV-2, as well as the need for new approaches to tackle the evolving virus.
Review
Immunology
William R. Strohl, Michael Naso
Review
Oncology
Michael F. Naso, Brian Tomkowicz, William L. Perry, William R. Strohl