Article
Immunology
Cooper J. Sailer, Yeonsun Hong, Ankit Dahal, Allison T. Ryan, Sana Mir, Scott A. Gerber, Patrick M. Reagan, Minsoo Kim
Summary: Chimeric antigen receptor (CAR)-T cell therapy shows promise in treating hematologic cancers, but its success in solid tumors is limited due to CAR-T cell exhaustion and poor persistence. This study finds that PD-1(high) CAR-T cells perform better in multiple T cell functions compared to PD-1(low) CAR-T cells. However, adoptive transfer of PD-1(high) CAR-T cells alone is insufficient to control tumor growth, and a combination therapy with PD-1 blockade is needed for solid tumors.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Cell & Tissue Engineering
Faroogh Marofi, Roza Motavalli, Vladimir A. Safonov, Lakshmi Thangavelu, Alexei Valerievich Yumashev, Markov Alexander, Navid Shomali, Max Stanley Chartrand, Yashwant Pathak, Mostafa Jarahian, Sepideh Izadi, Ali Hassanzadeh, Naghmeh Shirafkan, Safa Tahmasebi, Farhad Motavalli Khiavi
Summary: CAR T cells have shown significant advancements in treating blood disorders, but face challenges in solid tumor therapy due to issues with recognition, trafficking, and survival within the tumor. Efforts to overcome these challenges, including addressing the immunosuppressive tumor microenvironment, show promise in reducing T cell exhaustion and improving therapeutic outcomes in non-hematologic malignancies.
STEM CELL RESEARCH & THERAPY
(2021)
Review
Oncology
Julien Edeline, Roch Houot, Aurelien Marabelle, Marion Alcantara
Summary: CAR-T cells and BiTE immunotherapies have shown remarkable efficacy in treating B cell hematologic malignancies, but their application in solid tumors is challenging with early clinical trial results falling short of expectations. However, various strategies for improvement are currently being explored.
JOURNAL OF HEMATOLOGY & ONCOLOGY
(2021)
Article
Multidisciplinary Sciences
Hongjun Li, Zejun Wang, Edikan Archibong, Qing Wu, Guojun Chen, Quanyin Hu, Tianyuan Ci, Zhaowei Chen, Jinqiang Wang, Di Wen, Hongwei Du, Jie Jiang, Jie Sun, Xingcai Zhang, Gianpietro Dotti, Zhen Gu
Summary: A porous microneedle patch is used to load CAR T cells and escort them to solid tumors, breaking the physical barrier without losing cellular activity. This patch offers a transformative platform for scattered seeding of living cells for treating various tumors.
NATIONAL SCIENCE REVIEW
(2022)
Article
Chemistry, Multidisciplinary
Xinyue Wang, Fanyan Meng, Xiang Li, Luxin Xue, Anni Chen, Yuling Qiu, Zhifan Zhang, Lin Li, Fengcen Liu, Yishan Li, Zhichen Sun, Yanhong Chu, Ruihan Xu, Lixia Yu, Jie Shao, Manman Tian, Xiaoping Qian, Qin Liu, Baorui Liu, Rutian Li
Summary: Chimeric antigen receptor (CAR)-T cell therapy is an effective treatment against advanced malignancies, but it can cause severe adverse events. A nanomodified switch strategy using gelatinase-responsive nanoparticles (NPs) selectively delivers a heterodimerizing switch to activate CAR-T cells only on tumors. The sustained-release effect of NPs ensures smooth activation of CAR-T cells, avoiding sudden cytokine release. This study introduces NanoSwitch as a universal and applicable solution for safety problems in CAR-T therapy.
Review
Pharmacology & Pharmacy
Hassan Dana, Ghanbar Mahmoodi Chalbatani, Seyed Amir Jalali, Hamid Reza Mirzaei, Stephan A. Grupp, Eloah Rabello Suarez, Catarina Raposo, Thomas J. Webster
Summary: New approaches in cancer immunotherapy, such as checkpoint inhibitors for solid tumors and CAR-T cell therapy for hematologic malignancies, have shown promising results. While CAR-T products have demonstrated powerful effects against B cell cancers, challenges exist in using them for solid tumors.
ACTA PHARMACEUTICA SINICA B
(2021)
Article
Biochemistry & Molecular Biology
Sachiko Hirobe, Seina Nagai, Masashi Tachibana, Naoki Okada
Summary: Chimeric antigen receptor expression T (CAR-T) cell therapy has shown efficacy against relapsed/refractory B-cell malignant lymphoma and is considered an innovative cancer treatment. CAR-T cells targeting roundabout homolog 4 (Robo4), which is highly expressed in tumor vascular endothelial cells, have been constructed to overcome the challenges of solid tumor accessibility and immunosuppressive tumor microenvironment. These CAR-T cells exhibit antigen-specific cytotoxicity, cytokine production, and proliferation correlated with their binding affinity for Robo4.
Review
Pharmacology & Pharmacy
Zheng-Zheng Zhang, Tian Wang, Xiao-Feng Wang, Yu-Qing Zhang, Shu-Xia Song, Cui-Qing Ma
Summary: Chimeric antigen receptor T cell (CAR-T) therapy has shown significant progress in the treatment of hematologic malignancies, with higher specificity, stronger lethality, and longer-lasting efficacy compared to traditional anti-tumor methods. However, there are still challenges in the treatment of solid tumors, including immune escape, physical barriers, immunosuppressive molecules, and T cell exhaustion. Modifying intracellular signaling of CAR, coexpressing or knocking out transcription factors, and combining CAR-T cells with other therapies are promising strategies to improve CAR-T cells function.
PHARMACOLOGICAL RESEARCH
(2022)
Article
Oncology
Boon Kiat Lee, Yuhua Wan, Zan Lynn Chin, Linyan Deng, Mo Deng, Tze Ming Leung, Jian Hua, Hua Zhang
Summary: ROR1 CAR-T cells derived from Zilovertamab have been shown to specifically target ROR1(+) solid tumors with high efficacy and safety in vitro and in vivo, making them a promising therapeutic option for future clinical applications.
Review
Immunology
Arthur Xuan Wang, Xiao Jing Ong, Criselle D'Souza, Paul J. Neeson, Joe Jiang Zhu
Summary: Chemotherapy is commonly used before CAR-T cell therapy to improve engraftment. It can deplete immunosuppressive cells, promote a pro-inflammatory tumor microenvironment, disrupt tumor stroma, and improve CAR-T cell recruitment. However, there are challenges and obstacles to achieving effective clinical outcomes with the combination therapy, such as dosage and treatment schedule-dependent effects.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Biotechnology & Applied Microbiology
Yibo Yin, Jesse L. Rodriguez, Nannan Li, Radhika Thokala, MacLean P. Nasrallah, Li Hu, Logan Zhang, Jiasi Vicky Zhang, Meghan T. Logun, Devneet Kainth, Leila Haddad, Yang Zhao, Tong Wu, Emily X. Johns, Yu Long, Hongsheng Liang, Jiping Qi, Xiangtong Zhang, Zev A. Binder, Zhiguo Lin, Donald M. O'Rourke
Summary: Bispecific T cell engagers (BiTEs), which redirect T cells to target antigen-expressing tumors, have potential therapeutic effects in solid tumors. In our study using glioblastomas as a model, we found that BiTE-secreting T cells showed prominent activation, cytokine production, and cytotoxicity against the tumor antigens compared to CAR T cells. Bivalent BiTE-secreting T cells also demonstrated superior response activity in the early phase of a glioma mouse model. This suggests that BiTEs secreted by mono- or multi-valent T cells have potent anti-tumor activity, making them a promising strategy in solid tumor therapy.
Review
Oncology
Xin-Ying Tang, Yu-Shi Ding, Tao Zhou, Xu Wang, Yong Yang
Summary: CAR-T cell therapy has shown promising results in hematologic malignancies, but its efficacy in solid tumors is limited due to antigen heterogeneity, suboptimal trafficking, and immunosuppressive microenvironment. Combination with oncolytic viruses (OV) might be a novel solution to overcome these challenges and improve the therapeutic outcomes for non-hematologic malignancies.
Article
Medicine, Research & Experimental
Yizhao Chen, Zhiying Yu, Xuewen Tan, Haifeng Jiang, Zhen Xu, Yilong Fang, Dafei Han, Wenming Hong, Wei Wei, Jiajie Tu
Summary: CAR-M therapy shows potential in targeting solid tumors, but there are limitations that need further research to enhance its therapeutic efficacy.
BIOMEDICINE & PHARMACOTHERAPY
(2021)
Review
Biochemistry & Molecular Biology
Parvin Akbari, Afroditi Katsarou, Roxanna Daghighian, Lotte W. H. G. van Mil, Elisabeth J. M. Huijbers, Arjan W. Griffioen, Judy R. van Beijnum
Summary: In this review, recent advances in CAR T cell therapy against solid tumors, with a focus on targeting the tumor vasculature, are discussed. Opportunities to overcome challenges and barriers through engineering of CAR T cells to enhance trafficking, safety, and efficacy are also explored.
BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER
(2022)
Article
Biology
Francesco Mainini
Summary: Adoptive cell therapy and Immune Checkpoint Blockade Inhibitors have revolutionized oncology, but have limited success in treating solid tumors. The field of nanobiotechnology is rapidly expanding in oncology, with nanoparticles-based delivery systems enhancing the efficacy of CAR-T cells.
Review
Hematology
Benjamin Heyman, Yiping Yang
EXPERIMENTAL HEMATOLOGY
(2016)
Letter
Oncology
B. Heyman, A. D. Volkheimer, J. B. Weinberg
BLOOD CANCER JOURNAL
(2016)
Article
Immunology
Maria K. Abril, Adam S. Barnett, Kara Wegermann, Eric Fountain, Andrew Strand, Benjamin M. Heyman, Britton A. Blough, Aparna C. Swaminathan, Batu Sharma-Kuinkel, Felicia Ruffin, Barbara D. Alexander, Chad M. McCall, Sylvia F. Costa, Murat O. Arcasoy, David K. Hong, Timothy A. Blauwkamp, Michael Kertesz, Vance G. Fowler, Bryan D. Kraft
OPEN FORUM INFECTIOUS DISEASES
(2016)
Article
Oncology
Benjamin Heyman, David Rizzieri, David J. Adams, Carlos De Castro, Louis Diehl, Zhiguo Li, Joseph Moore, Anne Beaven
CLINICAL LYMPHOMA MYELOMA & LEUKEMIA
(2018)
Review
Oncology
Benjamin Heyman, Anne Beaven
CLINICAL LYMPHOMA MYELOMA & LEUKEMIA
(2018)
Review
Oncology
Benjamin Heyman, Yiping Yang
CANCER BIOLOGY & MEDICINE
(2018)
Review
Oncology
Benjamin M. Heyman, Dimitrios Tzachanis, Thomas J. Kipps
Summary: Outcomes for patients with chronic lymphocytic leukemia (CLL) have improved with targeted therapies, but options are limited for refractory or intolerant patients. Chimeric antigen receptor T cell therapy (CAR T cell) holds promise as a potential treatment for high-risk CLL patients. This article reviews the literature and treatment considerations of CAR T cell therapy for CLL patients.
Article
Oncology
Benjamin M. Heyman, Michael Y. Choi, Thomas J. Kipps
Summary: Patients with Richter's Syndrome have a poor prognosis and traditional treatments are not effective. In this study, a novel chemotherapy-free combination of obinutuzumab, high-dose methylprednisolone, and lenalidomide was used to treat Richter's Syndrome patients, showing promising results.
Article
Oncology
Tamer Othman, Michelle A. Quan, Shiliang Zhang, Daria Gaut, Patricia A. Young, Omar Mahmood, Haifaa Abdulhaq, Kevin Shieh, Jack Reid, Elizabeth A. Brem, Nisha Hariharan, Benjamin Heyman, Joseph Tuscano
Summary: This study retrospectively analyzed PCNSL patients who received autologous hematopoietic cell transplantation or nonmyeloablative chemotherapy in CR1. The results showed that autologous hematopoietic cell transplantation in CR1 can improve outcomes in eligible patients.
CLINICAL LYMPHOMA MYELOMA & LEUKEMIA
(2023)
Review
Oncology
Chung-Jiah J. Chen, Michael Y. Choi, Benjamin M. Heyman
Summary: Targeted therapies have shown promise in the treatment of follicular lymphoma (FL) by inhibiting key molecular pathways responsible for cancer proliferation and survival. These therapies, including immune modulators, anti-CD20 antibodies, BTK inhibitors, EZH2 inhibitors, PI3K inhibitors, and BCL-2 inhibitors, have high overall response rates and substantial progression-free survival and overall survival. CAR-T therapy and BiTE therapies also show promise in monotherapy and in combination with targeted therapies. Adverse events are generally manageable and compare favorably to the cumulative toxicities of chemotherapy.
Article
Medicine, General & Internal
Benjamin M. Heyman, Matthew J. Chung, Amy L. Lark, Scott Shofer
AMERICAN JOURNAL OF CASE REPORTS
(2013)
