Review
Immunology
Laetitia Pinte, Amy Cunningham, Helene Trebeden-Negre, Sarah Nikiforow, Jerome Ritz
Summary: CAR and TCR therapies have shown unprecedented growth since the first genetically-engineered clinical trial in 2003, with the USA, China, and Europe emerging as major research sites. Novel targets, genetic constructs, and manufacturing strategies are being developed to optimize efficacy and safety in treating various types of cancer.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Immunology
Wenshuai Li, Xuanxuan Pan, Lirong Chen, Haoshu Cui, Shaocong Mo, Yida Pan, Yuru Shen, Menglin Shi, Jianlin Wu, Feifei Luo, Jie Liu, Na Li
Summary: Adoptive cell therapy (ACT) using chimeric antigen receptor (CAR)-modified T cells has shown remarkable efficacy against hematological malignancies, but its success in solid tumors is limited by factors such as easy recurrence and poor efficacy. The effector function and persistence of CAR-T cells are critical to the success of therapy and are modulated by metabolic and nutrient-sensing mechanisms. Moreover, the immunosuppressive tumor microenvironment (TME) can lead to T cell exhaustion and compromise the efficacy of CAR-T cells. This review discusses the metabolic characteristics of T cells and potential metabolic approaches to improve the efficacy and persistence of CAR-T cells.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Oncology
Yu-Ge Zhu, Bu-Fan Xiao, Jing-Tao Zhang, Xin-Run Cui, Zhe-Ming Lu, Nan Wu
Summary: Esophageal cancer is a highly aggressive and malignant cancer that can be treated with surgery, chemotherapy, radiotherapy, and immunotherapy. Immunotherapy, specifically using genetically-modified cells to target cancer cells, has shown promising results in clinical trials.
FRONTIERS IN ONCOLOGY
(2021)
Article
Biotechnology & Applied Microbiology
Jingting Min, Chirong Long, Lu Zhang, Jiakang Duan, Honglian Fan, Fei Chu, Zhenghong Li
Summary: Non-small cell lung cancer (NSCLC) is a prevalent and fatal malignancy, and CAR-T cell therapy targeting c-Met shows potential as a therapeutic strategy. In vitro and in vivo experiments demonstrated that c-Met CAR-T cells exhibit enhanced cytotoxicity against NSCLC cells.
Article
Oncology
Satomi Okada, Daisuke Muraoka, Kiyoshi Yasui, Isao Tawara, Ayumi Kawamura, Sachiko Okamoto, Junichi Mineno, Naohiro Seo, Hiroshi Shiku, Susumu Eguchi, Hiroaki Ikeda
Summary: Adoptive immunotherapy using genetically engineered lymphocytes is a promising treatment for malignancy. This study evaluated the anti-tumor efficacy of T cells engineered with a high-affinity TCR and their potential to induce GVHD. Results showed that gene-modified T cells effectively regressed tumors without causing GVHD, suggesting the potential of off-the-shelf therapy for patients with malignancy.
Review
Biology
Dongdong Ti, Miaomiao Bai, Xiaolei Li, Jianshu Wei, Deyun Chen, Zhiqiang Wu, Yao Wang, Weidong Han
Summary: Impaired tumor-specific effector T cells lead to tumor progression and unfavorable clinical outcomes, but adoptive T cell therapy (ACT) has emerged as a promising strategy in cancer treatment, involving ex vivo stimulation and expansion of tumor-infiltrating lymphocytes or genetically modified T cells to provide efficient and long-lasting immune defense against transformed cells.
SCIENCE CHINA-LIFE SCIENCES
(2021)
Article
Multidisciplinary Sciences
Sara Valpione, Piyushkumar A. Mundra, Elena Galvani, Luca G. Campana, Paul Lorigan, Francesco De Rosa, Avinash Gupta, John Weightman, Sarah Mills, Nathalie Dhomen, Richard Marais
Summary: High baseline T cell receptor diversity is predictive of favorable prognosis in multiple cancer types, while monoclonal expansion of T cells pre-treatment correlates with good response to immune checkpoint blockade therapy in metastatic melanoma patients.
NATURE COMMUNICATIONS
(2021)
Article
Hematology
Paul M. Maciocia, Patrycja A. Wawrzyniecka, Nicola C. Maciocia, Amy Burley, Thaneswari Karpanasamy, Sam Devereaux, Malika Hoekx, David O'Connor, Theresa Leon, Tanya Rapoz-D'Silva, Rachael Pocock, Sunniyat Rahman, Giuseppe Gritti, Diana C. Yanez, Susan Ross, Tessa Crompton, Owen Williams, Lydia Lee, Martin A. Pule, Marc R. Mansour
Summary: CCR9 expression is found in the majority of T-ALL cases, making it a potential target for CAR-T cell therapy. CAR-T cells targeting CCR9 can effectively inhibit leukemia cell proliferation without harming healthy T cells, providing a promising treatment strategy for T-ALL.
Article
Oncology
Piriya Luangwattananun, Mutita Junking, Jatuporn Sujjitjoon, Yupanun Wutti-in, Naravat Poungvarin, Chanitra Thuwajit, Pa-thai Yenchitsomanus
Summary: The study demonstrates the specificity of fourth-generation FR alpha-CAR T cells in lysing breast cancer cells and their anti-tumor activity in spheroid cultures.
BREAST CANCER RESEARCH AND TREATMENT
(2021)
Article
Immunology
Nuo Xu, Douglas C. Palmer, Alexander C. Robeson, Peishun Shou, Hemamalini Bommiasamy, Sonia J. Laurie, Caryn Willis, Gianpietro Dotti, Benjamin G. Vincent, Nicholas P. Restifo, Jonathan S. Serody
Summary: The study demonstrates that enhancing CAR T cell therapy targeting solid tumors with STING agonists, specifically DMXAA, can greatly improve tumor control by promoting CAR T cell trafficking and persistence in the tumor microenvironment. The single-cell RNA sequencing results show that DMXAA generates a chemokine milieu that facilitates CART cell recruitment and modulates the immunosuppressive TME.
JOURNAL OF EXPERIMENTAL MEDICINE
(2021)
Review
Immunology
Paul Shafer, Lauren M. Kelly, Valentina Hoyos
Summary: This article presents a review of the use of engineered T cells for cancer therapy. The mechanisms of T cell antigen recognition and signal transduction mediated through CARs and TCRs are discussed, along with the current classes of cancer antigens recognized by TCR T therapies and pre-clinical strategies for TCR discovery and enhancement. The current landscape of clinical trials for TCR T therapy is also reviewed, providing insights into the development of future engineered TCR approaches.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Vahid Yekehfallah, Saghar Pahlavanneshan, Ali Sayadmanesh, Zahra Momtahan, Bin Ma, Mohsen Basiri
Summary: Chimeric antigen receptor (CAR) T-cell therapy has shown promising results in treating hematopoietic malignancies. However, the lack of specific tumor antigens with low expression in healthy cells is a challenge in solid tumors. This study constructed and evaluated CAR T cells targeting placental alkaline phosphatase (PLAP) antigen, showing that PLAP CAR T cells not only proliferated but also eliminated cancer cells in vitro. Increased secretion of IL-2, granzyme A, and IFN-gamma was observed in PLAP CAR T cells upon exposure to target cells. PLAP CAR T cells are potential candidates for further investigation in cervical cancer and other solid tumors.
Article
Chemistry, Medicinal
Meihui Yi, Zhaoqianqi Feng, Hongjian He, Daniela Dinulescu, Bing Xu
Summary: Cancer is a major public health concern and enzyme-instructed self-assembly (EISA) provides a unique approach for selectively inhibiting cancer cells. This study investigates EISA substrates of alkaline phosphatase (ALP) to hinder ovarian cancer cells. The results indicate that substrate 1 has the highest cytotoxicity against ovarian cancer cells, but there is limited synergism observed between substrate 1 and clinically used drugs. Further elucidation is needed to understand the distinct mechanism of EISA.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Review
Oncology
Samane Abbasi, Milad Asghari Totmaj, Masoumeh Abbasi, Saba Hajazimian, Pouya Goleij, Javad Behroozi, Behrouz Shademan, Alireza Isazadeh, Behzad Baradaran
Summary: Over the last decade, novel therapeutic approaches like CAR-T-cell immunotherapy have transformed the treatment perspective of human malignancies. However, this therapy is associated with side effects and faces challenges in manufacturing, engineering, applications, and toxicities. Further studies are needed to enhance efficacy and minimize adverse events.
Article
Surgery
Anil Kumar Mavi, Sonal Gaur, Gauri Gaur, Pragya Babita, Pragya Jindal, Neelesh Kumar, Umesh Kumar
Summary: CAR-T cell therapy is a major breakthrough in cancer treatment, but it faces various challenges in solid tumors and hematological malignancies. Severe toxicities, poor anti-tumor effectiveness, antigen escape, restricted trafficking, and limited tumor penetration are barriers to successful CAR-T cell treatment. Additionally, the interactions between CAR-T cells and the host and tumor microenvironment significantly impact their activity. Therefore, innovative methodologies are needed to engineer more potent CAR-T cells with greater anti-tumor activity and less toxicity.
ASIAN JOURNAL OF SURGERY
(2023)
Article
Oncology
Xinghuo Li, Anthony F. Daniyan, Andrea V. Lopez, Terence J. Purdon, Renier J. Brentjens
Summary: CAR T-cell therapy has shown significant efficacy in B-cell malignancies, but the lack of persistence and immune escape present challenges. By secreting IL-36 gamma, CAR T cells demonstrated improved expansion and persistence, resulting in enhanced tumor eradication. IL-36 gamma also activated endogenous APCs and T cells, delaying the progression of antigen-negative tumors. These findings support the translation of this design for a more effective CAR T-cell-mediated antitumor response.
Article
Dermatology
Andrea J. Lopez, Laura M. Jones, Landrye Reynolds, Rachel C. Diaz, Isaiah K. George, William Little, Derek Fleming, Anna D'souza, Monique Y. Rennie, Kendra P. Rumbaugh, Allie Clinton Smith
Summary: This study demonstrated the detection of porphyrin-producing bacteria within biofilms using bacterial fluorescence imaging in vivo, with red fluorescence readily detectable in wounds 48 hours after inoculation. The findings highlight the potential importance of this technology in biofilm research and early detection in clinical settings.
INTERNATIONAL WOUND JOURNAL
(2021)
Review
Engineering, Biomedical
Biaggio Uricoli, Lacey A. Birnbaum, Priscilla Do, James M. Kelvin, Juhi Jain, Emma Costanza, Andrew Chyong, Christopher C. Porter, Sarwish Rafiq, Erik C. Dreaden
Summary: Cytokine signaling plays a crucial role in biological processes such as cell development, tissue repair, and immunity, and can also be utilized as immunotherapies. However, challenges such as poor circulation limit their therapeutic potential. Recent advancements in engineering cytokines have focused on strategies across different size scales to enhance their effectiveness in treating diseases like cancer and autoimmune disorders.
ADVANCED HEALTHCARE MATERIALS
(2021)
Review
Oncology
Alysa N. Evans, Heather K. Lin, A. K. M. Nawshad Hossian, Sarwish Rafiq
Summary: Modifying CAR T cells to secrete different classes of proteins aims to optimize their function, overcome suppressive signals, and alter the tumor microenvironment. This approach is designed to enhance initial responses to therapy and increase the durability of response.
Article
Oncology
Nora E. Rahmani, Nandini Ramachandra, Srabani Sahu, Nadege Gitego, Andrea Lopez, Kith Pradhan, Tushar D. Bhagat, Shanisha Gordon-Mitchell, Bianca Rivera Pena, Mohammad Kazemi, Keshav Rao, Orsi Giricz, Shahina Bano Maqbool, Raul Olea, Yongmei Zhao, Jinghang Zhang, Hamid Dolatshad, Vickram Tittrea, Dharamveer Tatwavedi, Shalini Singh, Juseong Lee, Tianyu Sun, Ulrich Steidl, Aditi Shastri, Daichi Inoue, Omar Abdel-Wahab, Andrea Pellagatti, Evripidis Gavathiotis, Jacqueline Boultwood, Amit Verma
Summary: The study suggests that leukemia cells with ASXL1 mutations are more sensitive to Venetoclax and Azacytidine, possibly due to the upregulation of BCL2 expression and DNA methylation changes caused by ASXL1 mutations. These results reveal the potential effectiveness of these therapeutic drugs for leukemia patients.
BLOOD CANCER JOURNAL
(2021)
Article
Engineering, Biomedical
Hsin-ya Yang, Fernando Fierro, Daniel J. Yoon, Anthony Gallegos, Stephanie L. Osborn, Alan Nguyen, Thomas R. Peavy, William Ferrier, Linda Talken, Betty W. Ma, Kristopher G. Galang, Andrea Medina Lopez, Daniel R. Fregoso, Heather Stewart, Eric A. Kurzrock, Athena M. Soulika, Jan A. Nolta, R. Rivkah Isseroff
Summary: A combination treatment involving human mesenchymal stem/stromal cells (MSCs) embedded in an extracellular matrix scaffold and preconditioned with hypoxia and the beta-adrenergic receptor antagonist timolol, combined with sustained application of timolol post implantation, has shown promising results for improving wound healing in a diabetic mouse model. This study extends those findings to a porcine wound model, further demonstrating the efficacy and safety of the combined treatment in promoting wound reepithelialization and angiogenesis while maintaining a safe concentration of timolol in the plasma.
JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART B-APPLIED BIOMATERIALS
(2022)
Review
Biotechnology & Applied Microbiology
A. K. M. Nawshad Hossian, Christopher S. Hackett, Renier J. Brentjens, Sarwish Rafiq
Summary: T cells genetically engineered with synthetic chimeric antigen receptors (CARs) have shown remarkable clinical efficacy against B cell leukemia. With FDA approval of CAR T cell products, this highly personalized therapy has been validated as a powerful new drug against cancer. Researchers are now investigating ways to expand this technology beyond its use in cancer and apply it to other diseases.
Article
Public, Environmental & Occupational Health
Andrea M. Lopez, Matthew Thomann, Zena Dhatt, Julieta Ferrera, Marwa Al-Nassir, Margaret Ambrose, Shane Sullivan
Summary: This study aims to elucidate a structurally oriented theoretical framework that considers legacies of racism, trauma, and social exclusion, and to interrogate the unmet obligations of the harm reduction infrastructure in providing equitable protections to Black and Latinx people who use drugs in Maryland. The research found that the unmet obligations included enforcement and punitive governance of drug use equipment, racism and social exclusion, and differential implications of harm reduction for different populations experiencing racialized criminalization.
AMERICAN JOURNAL OF PUBLIC HEALTH
(2022)
Article
Multidisciplinary Sciences
Andrea Lopez, Denis E. Reyna, Nadege Gitego, Felix Kopp, Hua Zhou, Miguel A. Miranda-Roman, Lars Ulrik Nordstrom, Swathi-Rao Narayanagari, Ping Chi, Eduardo Vilar, Aristotelis Tsirigos, Evripidis Gavathiotis
Summary: Deregulation of the BCL-2 family interaction network is a major challenge in cancer treatment. This study presents a novel therapeutic strategy to overcome two anti-apoptotic mechanisms in cancer through the combination of a BAX activator and Navitoclax.
NATURE COMMUNICATIONS
(2022)
Article
Economics
Jaime L. Rubin, Andrea Lopez, Jason Booth, Penilla Gunther, Anupam B. Jena
Summary: This study examines the impact of modifications to standard cost-effectiveness analysis methods on measures of cost-effectiveness for rare chronic diseases, finding that modifying assumptions for discounting rates, utility measures, disease management costs, and drug pricing can significantly reduce the incremental cost-effectiveness ratio.
JOURNAL OF MEDICAL ECONOMICS
(2022)
Article
Hospitality, Leisure, Sport & Tourism
Andrea Lopez, Raimundo Sanchez
Summary: This study examined the personality traits of trail runners in a competition in Chile using the NEO-FFI questionnaire. The results showed that successful mountain runners exhibited high Conscientiousness and low Neuroticism, but there were no significant differences in Openness to Experience compared to the normal population. There were also no significant differences in traits between ultradistance and shorter distance runners, or based on motivations and gender (except for Agreeableness). The findings have practical implications for sports practitioners in designing interventions based on athletes' personality profiles and challenging gender stereotypes in sports.
RETOS-NUEVAS TENDENCIAS EN EDUCACION FISICA DEPORTE Y RECREACION
(2023)
Correction
Public, Environmental & Occupational Health
Andrea M. Lopez, Matthew Thomann, Zena Dhatt, Julieta Ferrera, Marwa Al-Nassir, Maggie Ambrose, Shane Sullivan
AMERICAN JOURNAL OF PUBLIC HEALTH
(2022)
Meeting Abstract
Respiratory System
Andrea Samantha Hernandez Lopez, Arturo Orea Tejeda, Dulce Gonzalez Islas, Susana Galicia Amor, Esperanza Trejo Mellado, Juan Carlos Garcia Hernandez, Maria Fernanda Salgado Fernandez, Carlos Miguel Sanchez Moreno
EUROPEAN RESPIRATORY JOURNAL
(2021)
Article
Substance Abuse
Andrea M. Lopez, Zena Dhatt, Mary Howe, Marwa Al-Nassir, Amy Billing, Eleanor Artigiani, Eric D. Wish
Summary: The study in the United States found that rates of methamphetamine use and methamphetamine-related deaths have been increasing, with methamphetamine increasingly present in opioid-related deaths. The research indicated that individuals testing positive for methamphetamine were on average five years younger than those testing negative, and nonfentanyl opioids were more common in methamphetamine positive specimens. This study suggests a need for further understanding of the co-use of methamphetamine and opioids in the context of larger socio-structural and community factors.
INTERNATIONAL JOURNAL OF DRUG POLICY
(2021)
Meeting Abstract
Health Care Sciences & Services
Andrea Lopez, Jaime Rubin
MEDICAL DECISION MAKING
(2021)