Article
Biochemistry & Molecular Biology
William G. J. Kerrison, Alexander T. J. Lee, Khin Thway, Robin L. Jones, Paul H. Huang
Summary: Immunotherapy in soft tissue sarcoma has become a popular and promising therapeutic strategy, with immune checkpoint inhibitors showing effectiveness in certain subtypes. Combination therapies have also shown enhanced response rates.
Article
Oncology
Fengguang Guo, Jugal K. Das, Koichi S. Kobayashi, Qing-Ming Qin, Thomas A. Ficht, Robert C. Alaniz, Jianxun Song, Paul De Figueiredo
Summary: This study demonstrates that live attenuated bacterial treatment can improve antitumor immunity by remodeling the tumor microenvironment, overcoming cancer resistance to chimeric antigen receptor T-cell therapy.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Article
Pharmacology & Pharmacy
Mengmeng Liu, Quan Li, Yao Liang
Summary: Several studies have identified pyroptosis as a potential target for cancer treatment. This study specifically focuses on the role of pyroptosis-related genes (PRGs) in soft tissue sarcoma (STS) and evaluates their interactions, biological functions, and prognostic values. Through analysis, a five-gene survival related-risk score is created and validated in different cohorts. A nomogram is also developed to predict prognosis and therapeutic responses, and the study suggests that immunotherapy is more beneficial for patients with minimal risk of PRGs. Additionally, effective chemotherapy and targeted drugs sensitive to high-risk populations are identified.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Immunology
Kayla L. Marritt, Karys M. Hildebrand, Kurt N. Hildebrand, Arvind K. Singla, Franz J. Zemp, Douglas J. Mahoney, Frank R. Jirik, Michael J. Monument
Summary: This study assessed the therapeutic response of intratumoral STING activation in an immunologically cold murine model of undifferentiated pleomorphic sarcoma (UPS). The results showed that a single intratumoral injection of the murine STING agonist resulted in durable cure in up to 60% of UPS-bearing mice. In mice with synchronous lung metastases, STING activation within hindlimb tumors also resulted in 50% cure in both anatomic sites.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Immunology
Elisa Cappuzzello, Emilia Vigolo, Giulia D'Accardio, Giuseppe Astori, Antonio Rosato, Roberta Sommaggio
Summary: The successful treatment of B-cell malignancies with CAR-T cells was a breakthrough, but not all patients can benefit from this therapy. CIK cells, as an alternative cellular therapy, have the potential to overcome some of the limitations of CAR-T cells.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Martin J. Raftery, Alexander Sebastian Franzen, Clarissa Radecke, Abdelhadi Boulifa, Guenther Schoenrich, Sebastian Stintzing, Jens-Uwe Blohmer, Gabriele Pecher
Summary: There is a medical need to develop new and effective therapies against triple-negative breast cancer (TNBC). We have developed a next-generation CAR targeting CD44v6 that incorporates IL-15 superagonist and checkpoint inhibitor molecules. CD44v6 CAR-NK cells demonstrated effective cytotoxicity against TNBC in 3D spheroid models and were resistant to immunosuppression by the tumor microenvironment.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Oncology
Thomas Kimman, Anne Slomp, Anne Martens, Sarah Grabherr, Shuang Li, Eline van Diest, Jan Meeldijk, Jurgen Kuball, Monique C. Minnema, Eric Eldering, Niels Bovenschen, Zsolt Sebestyen, Victor Peperzak
Summary: Gene engineered CAR T cells have shown promising initial clinical responses in cancer patients; however, resistance mechanisms in cancer cells can limit the effectiveness of CAR T cell-mediated killing. Serpin B9 expression in cancer cells can lead to resistance towards CAR T cells, and inhibiting or bypassing serpin B9 may improve CAR T cell responses.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2023)
Article
Biotechnology & Applied Microbiology
Kang-Wen Xiao, Zhi-Qiang Yang, Xin Yan, Zhi-Bo Liu, Min Yang, Liang-Yu Guo, Lin Cai
Summary: By analyzing the characteristics and patterns of m6A modification in soft tissue sarcoma (STS), this study identified two different modification patterns and found that m6A cluster A had better clinical outcomes and lower immune/stromal scores compared to m6A cluster B. Additionally, the m6Ascore effectively predicted the characteristics and prognosis of STS, as well as the outcome of PD-1/PD-L1 blockade immunotherapy.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2022)
Article
Oncology
Yukiko Yamaguchi, Jackson Gibson, Kevin Ou, Lupita S. Lopez, Rachel H. Ng, Neena Leggett, Vanessa D. Jonsson, Jelani C. Zarif, Peter P. Lee, Xiuli Wang, Catalina Martinez, Tanya B. Dorff, Stephen J. Forman, Saul J. Priceman
Summary: This study reveals an alternative mechanism by which the combination of CAR T cells and immune checkpoint blockade modulates the immune landscape of solid tumors to enhance therapeutic efficacy of CAR T cells.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Article
Oncology
Yi-Chiu Kuo, Cheng-Fu Kuo, Kurt Jenkins, Alfur Fu-Hsin Hung, Wen-Chung Chang, Miso Park, Brenda Aguilar, Renate Starr, Jonathan Hibbard, Christine Brown, John C. Williams
Summary: The use of universal CAR T cells shows promise in improving the efficacy of cancer treatment and has broad potential applications.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Article
Immunology
Binfeng Liu, Chenbei Li, Chengyao Feng, Hua Wang, Haixia Zhang, Chao Tu, Shasha He, Zhihong Li
Summary: Given the poor prognosis of soft tissue sarcoma (STS), this study aimed to explore the association of angiogenesis-related genes (ARGs) with STS and establish a novel angiogenesis-related signature (ARSig). The ARSig was validated as a promising prognostic factor for STS and was found to be relevant to the tumor immune microenvironment, tumor mutational burden (TMB), and therapeutic response. In vitro experiments further confirmed the dysregulation of signature ARGs and their role in the malignant progression of STS cells. This study provides a new strategy for prognostic assessment and personalized treatment of STS.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Multidisciplinary Sciences
Liora M. Schultz, Debra K. Czerwinski, Ronald Levy, Shoshana Levy
Summary: This study investigates the effect of CD81 costimulation on CAR transduction, finding that it enhances naive T cell activation and results in a CAR T cell product enriched with naive-derived CART cells.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Review
Immunology
Yanling Liang, Qumiao Xu, Qianqian Gao
Summary: This review outlines the important roles of macrophages and neutrophils in the tumor microenvironment and their potential in cancer immunotherapy. It focuses on CAR-engineered macrophages (CAR-Ms) and neutrophils (CAR-Ns), discussing their construction strategies, preclinical and clinical studies. The limitations, challenges, and future research directions of CAR-Ms and CAR-Ns are also briefly discussed.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Oncology
John E. Mullinax, MacLean Hall, Matthew Beatty, Amy M. Weber, Zachary Sannasardo, Tanja Svrdlin, Jonathan Hensel, Marilyn Bui, Allison Richards, Ricardo J. Gonzalez, Cheryl A. Cox, Linda Kelley, James J. Mule, Amod A. Sarnaik, Shari Pilon-Thomas
Summary: This study successfully developed methods to expand tumor-reactive TIL from resected soft tissue sarcoma, demonstrating the feasibility and effectiveness of using TIL for treatment. The TIL cultures were responsive to autologous tumor and could be expanded to clinically relevant numbers following a rapid expansion protocol. These findings have led to an active ACT clinical trial approved for patients with metastatic soft tissue sarcoma.
JOURNAL OF IMMUNOTHERAPY
(2021)
Article
Oncology
Diego Sanchez Martinez, Nestor Tirado, Sofia Mensurado, Alba Martinez-Moreno, Paola Romecin, Francisco Gutierrez Aguera, Daniel Correia, Bruno Silva-Santos, Pablo Menendez
Summary: This study generated and preclinically validated 4-1BB-based CAR-DOTs targeting CD123, showing vigorous and superior cytotoxicity against AML cells, providing proof-of-concept for using DOTs as a next-generation allogeneic CAR-T therapy for AML.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Article
Hematology
Paola Circosta, Chiara Donini, Susanna Gallo, Lidia Giraudo, Loretta Gammaitoni, Ramona Rotolo, Federica Galvagno, Sonia Capellero, Marco Basirico, Monica Casucci, Massimo Aglietta, Ivana Ferrero, Franca Fagioli, Alessandro Cignetti, Fabrizio Carnevale-Schianca, Valeria Leuci, Dario Sangiolo
Summary: This study explored the feasibility, anti-leukaemic activity, and alloreactive risk of genetically redirected CIK (fcCAR.CIK) generated from full-donor chimaeric patients. The results showed that fcCAR.CIK exhibited intense preclinical anti-leukaemic activity without enhancing the risk of graft-versus-host disease, supporting the potential use of fcCAR.CIK as an alternative to conventional donor lymphocyte infusion following haematopoietic cell transplantation.
BRITISH JOURNAL OF HAEMATOLOGY
(2023)
Article
Oncology
Ramona Rotolo, Valeria Leuci, Chiara Donini, Federica Galvagno, Annamaria Massa, Maria Chiara De Santis, Serena Peirone, Giovanni Medico, Martina Sanlorenzo, Igor Vujic, Loretta Gammaitoni, Marco Basirico, Luisella Righi, Chiara Riganti, Iris Chiara Salaroglio, Francesca Napoli, Fabrizio Tabbo, Annapaola Mariniello, Elisa Vigna, Chiara Modica, Lorenzo D'Ambrosio, Giovanni Grignani, Riccardo Taulli, Emilio Hirsch, Matteo Cereda, Massimo Aglietta, Giorgio Vittorio Scagliotti, Silvia Novello, Paolo Bironzo, Dario Sangiolo
Summary: This study reports a novel therapeutic activity of anti-PD-1 antibodies against non-small cell lung cancer (NSCLC), which can block the tumor-intrinsic PD-1 receptors on chemoresistant cells. PD-1 expression in NSCLC cells was found to increase after cisplatin treatment, and anti-PD-1 antibodies can inhibit the recovery of chemo-surviving cells. The study suggests that anti-PD-1 antibodies have a lymphocyte-independent activity in NSCLC and can be used to prevent disease relapses after chemotherapy.
CLINICAL CANCER RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Erika Fiorino, Alessandra Merlini, Lorenzo D'Ambrosio, Ilaria Cerviere, Enrico Berrino, Caterina Marchio, Lidia Giraudo, Marco Basirico, Annamaria Massa, Chiara Donini, Valeria Leuci, Ramona Rotolo, Federica Galvagno, Letizia Vitali, Alessia Proment, Soldano Ferrone, Alberto Pisacane, Ymera Pignochino, Massimo Aglietta, Giovanni Grignani, Giulia Mesiano, Dario Sangiolo
Summary: This study investigates the immunotherapy efficacy on imatinib and sunitinib-resistant wild-type gastrointestinal stromal tumors (wtGIST) using a patient-derived preclinical model. The results show that cytokine-induced killer lymphocytes (CIK) can kill resistant wtGIST cells, and interferons (IFN) have anti-tumor effects on certain resistant wtGIST cells. These findings support the exploration of CIK immunotherapy in clinical studies and the reevaluation of IFN within this challenging setting.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Oncology
Camilla Bove, Silvia Arcangeli, Laura Falcone, Barbara Camisa, Rita El Khoury, Beatrice Greco, Anna De Lucia, Alice Bergamini, Attilio Bondanza, Fabio Ciceri, Chiara Bonini, Monica Casucci
Summary: This study investigated the role of CD4 and CD8 T cells in CD19 CAR-T cell responses and the development of cytokine release syndrome (CRS). CD4 CAR-T cells exhibited superior proliferation and activation potential compared to CD8 CAR-T cells. CD4 CAR-T cells were found to play a key role in the development of CRS, and CD4 CAR-T cells with embedded 4-1BB were associated with a safer profile. CD4 cells were crucial for maintaining long-term responses and the combination of CD4.BBz with CD8.28z CAR-T cells resulted in the lowest toxicity without compromising antitumor efficacy.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2023)
Article
Oncology
Fabio Giglio, Edoardo Campodonico, Francesca Lorentino, Maddalena Noviello, Elisabetta Xue, Raffaella Greco, Lorenzo Lazzari, Alessandro Bruno, Maria Teresa Lupo Stanghellini, Matteo Giovanni Carrabba, Roberta La Starza, Monica Casucci, Chiara Bonini, Sabina Chiaretti, Jacopo Peccatori, Robin Foa, Fabio Ciceri
Summary: Philadelphia-like acute lymphoblastic leukemia (ALL), a subtype with poor prognosis, requires investigation in identifying mutations for targeted treatment with tyrosine kinase-inhibitors (TKIs). This study presents a unique case of using compassionate-use ponatinib and low-dose prednisone to bridge to chimeric antigen receptor T (CAR-T) cell therapy in a relapsed/refractory Ph-like ALL patient. Maintenance therapy with low-dose ponatinib was continued and achieved measurable residual disease negativity and B-cell aplasia 20 months later. This is the first reported case of using ponatinib as a bridge and maintenance therapy after CAR-T cell therapy in Ph-like ALL.
FRONTIERS IN ONCOLOGY
(2023)
Article
Biotechnology & Applied Microbiology
Ilenia Iaia, Virginia Brancato, David Caballero, Rui L. Reis, Massimo Aglietta, Dario Sangiolo, Subhas C. Kundu
Summary: Little is known about the role of fibroblasts in solid tumors such as melanoma and the mechanism behind it due to the lack of relevant pre-clinical models. In this report, a melanoma-on-a-chip model was proposed to evaluate the essential role of fibroblasts in the antitumor activity of lymphocytes. The presence of fibroblasts was observed to inhibit immune effector recruitment in a 3D pre-clinical tumor model.
BIOENGINEERING-BASEL
(2023)
Article
Oncology
Valentina Tuninetti, Eleonora Ghisoni, Sandro Pignata, Elisa Picardo, Francesco Raspagliesi, Claudia Andreetta, Elena Maldi, Grazia Artioli, Serafina Mammoliti, Lucia Zanchi, Angelica Sikokis, Nicoletta Biglia, Alessandro Parisi, Vincenzo Dario Mandato, Claudia Carella, Gennaro Cormio, Marco Marinaccio, Andrea Puppo, Biagio Paolini, Lucia Borsotti, Giulia Scotto, Margherita Turinetto, Dario Sangiolo, Massimo Di Maio, Giorgio Valabrega
Summary: The expression of Ki67 at diagnosis does not predict the response to PARP inhibitors in BRCA wild-type ovarian cancer patients.
Article
Oncology
Paola Zagami, Alessandro Comandone, Marco Fiore, Giacomo Giulio Baldi, Giovanni Grignani, Bruno Vincenzi, Alessandro Gronchi, Gabriele Antonarelli, Antonella Boglione, Elisabetta Pennacchioli, Giuseppe Curigliano, Fabio Conforti, Tommaso Martino De Pas
Summary: In this retrospective observational study, GI leiomyosarcomas (GI-LMS) were found to be a rare and highly aggressive subtype of sarcomas. Localized GI-LMS can be cured with appropriate surgery and adjuvant chemotherapy, while de-novo metastatic disease has a poor prognosis. Therefore, efforts are needed to understand the biology and clinical behavior of GI-LMS and develop effective treatment strategies.
Article
Medicine, Research & Experimental
Silvia Arcangeli, Camilla Bove, Claudia Mezzanotte, Barbara Camisa, Laura Falcone, Francesco Manfredi, Eugenia Bezzecchi, Rita El Khoury, Rossana Norata, Francesca Sanvito, Maurilio Ponzoni, Beatrice Greco, Marta Angiola Moresco, Matteo G. Carrabba, Fabio Ciceri, Chiara Bonini, Attilio Bondanza, Monica Casucci
Summary: This study investigated the efficacy and safety profiles of CAR T cell products generated from preselected naive/stem memory T cells (TN/SCM). The results showed that CAR TN/SCM cells exhibited stronger antitumor activity and were able to prevent leukemia relapse. Furthermore, CAR TN/SCM cells had a lower risk of inducing severe cytokine release syndrome, indicating a higher therapeutic index.
JOURNAL OF CLINICAL INVESTIGATION
(2022)