Review
Immunology
Suheil Albert Atallah-Yunes, Michael J. Robertson, Utpal P. Dave, Paola Ghione, Fabiana Perna
Summary: The prognosis for patients with refractory/relapsed diffuse large B-cell lymphoma (DLBCL) is poor. Immune-based therapeutic treatments such as CD19 Chimeric Antigen Receptor (CAR) T cell therapies have shown promising results, but there is a need for further development of novel therapies to improve outcomes for non-responsive or relapsed patients.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Health Care Sciences & Services
Jeremy A. Meier, Barbara Savoldo, Natalie S. Grover
Summary: Treatment for Hodgkin lymphoma has advanced significantly, but a portion of patients still experience relapse or disease progression. Immunotherapies, particularly CAR T cells, have shown exceptional promise in treating relapsed/refractory HL.
JOURNAL OF PERSONALIZED MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Yao Wang, Chuan Tong, Yuting Lu, Zhiqiang Wu, Yelei Guo, Yang Liu, Jianshu Wei, Chunmeng Wang, Qingming Yang, Weidong Han
Summary: CAR-T cell therapy has become an important treatment option for patients with relapsed/refractory B-cell malignancies, but a significant number of DLBCL patients fail to achieve durable response. This study analyzed the characteristics of pre-manufacture T cells and CAR-T cell products in DLBCL patients and identified the key role of CD8+ stem cell-like memory T cells in achieving durable clinical response. Heterogeneity in the cellular and molecular features of pre-manufacture T cells contributes to the variation in efficacy after CAR-T cell therapy, and loss of CCR7 gene expression and increased expression of activation- and inhibitor-related genes in CD8+ naive-T cell populations may explain the differences in anti-tumor efficacy among patients with different clinical outcomes.
SIGNAL TRANSDUCTION AND TARGETED THERAPY
(2023)
Review
Health Care Sciences & Services
Magdalena Ostojska, Emilia Nowak, Julia Twardowska, Monika Lejman, Joanna Zawitkowska
Summary: Non-Hodgkin lymphomas (NHL) is a type of cancer originating from the lymphatic system, and it is the fourth most common cancer among pediatric patients. Available medicines and therapies have improved the prognosis for NHL patients, but treatment resistance remains a challenge. Immunotherapy, specifically chimeric antigen receptor (CAR) T cell therapy, is becoming increasingly important as a targeted and personalized treatment strategy for pediatric patients with NHL. This review evaluates the effectiveness, safety, and limitations of CAR-T cell therapy.
JOURNAL OF PERSONALIZED MEDICINE
(2023)
Article
Medicine, Research & Experimental
Qingzhu Jia, Diyuan Qin, Feng He, Qichao Xie, Zhitao Ying, Yajing Zhang, Yuqin Song, Jia-Nan Cheng, Xuejiao Zuo, Luxiang Xu, Hongliang Fang, Chunyan Hu, Lina Peng, Tao Jin, Zixiao Shi, Peter B. Alexander, Yongsheng Wang, Yarong Liu, Weidong Han, Jun Zhu, Pin Wang, Qi-Jing Li, Bo Zhu
Summary: This study identified the baseline high eosinophil count as a potential biomarker for predicting the clinical efficacy of CAR-T cell therapy in B-NHL patients. A preclinical model demonstrated that depletion of eosinophils could impair the intratumoral infiltration and antitumor efficacy of CAR-T cells.
Article
Immunology
Jiachen Wang, Kefeng Shen, Wei Mu, Weigang Li, Meilan Zhang, Wei Zhang, Zhe Li, Tong Ge, Zhoujie Zhu, Shangkun Zhang, Caixia Chen, Shugang Xing, Li Zhu, Liting Chen, Na Wang, Liang Huang, Dengju Li, Min Xiao, Jianfeng Zhou
Summary: This study retrospectively evaluated the treatment outcomes of murine CD19/CD22 cocktail CAR T-cell therapy in 135 DLBCL patients. The study found that higher levels of lactate dehydrogenase before leukapheresis and lower cytokine release syndrome grade after CAR T-cell infusion were independent risk factors for T-cell dysfunction. Additionally, a variety of germline variants in genes related to T-cell immunity were significantly enriched in the group with T-cell defects.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Oncology
Sebastian Zundler, Francesco Vitali, Soraya Kharboutli, Simon Voelkl, Iris Polifka, Andreas Mackensen, Raja Atreya, Markus F. F. Neurath, Dimitrios Mougiakakos
Summary: We report a case of a 70-year-old female patient with diffuse large B cell lymphoma (DLBCL) treated with tisagenlecleucel, who developed chronic diarrhea with inflammatory bowel disease (IBD)-like colitis. CAR T cells were found to be enriched in the colon lamina propria and other diagnoses were ruled out. Therefore, we conclude that IBD-like colitis in this patient was associated with CAR T cell therapy and should be considered as a rare potential complication.
FRONTIERS IN ONCOLOGY
(2023)
Article
Immunology
Changju Qu, Rui Zou, Peng Wang, Qian Zhu, Liqing Kang, Nana Ping, Fan Xia, Hailing Liu, Danqing Kong, Lei Yu, Depei Wu, Zhengming Jin
Summary: This study demonstrates that CD19/CD22 dual-targeted CAR-T therapy, under a decitabine-containing lymphodepletion regimen, may be a safe and potent effective approach for patients with relapsed/refractory DLBCL.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Medicine, General & Internal
Hongwen Li, Wenting Song, Jiazhuo Wu, Zhuangzhuang Shi, Yuyang Gao, Jiwei Li, Lijuan Han, Jianxiang Zhang, Zhaoming Li, Yong Li, Mingzhi Zhang
Summary: In this study, four CAR-T cell lines were generated to evaluate their effectiveness against NKTCL cells. The results showed that these CAR-T cell lines exhibited significant cytotoxicity against NKTCL cells both in vitro and in vivo, indicating their potential therapeutic promise in treating NKTCL.
Article
Immunology
Paolo F. Caimi, Gabriela Pacheco Sanchez, Ashish Sharma, Folashade Otegbeye, Nausheen Ahmed, Patricio Rojas, Seema Patel, Sarah Kleinsorge Block, Jennifer Schiavone, Kayla Zamborsky, Kirsten Boughan, Antoinette Hillian, Jane Reese-Koc, Mikhail Maschan, Boro Dropulic, Rafick-Pierre Sekaly, Marcos De Lima
Summary: In this study, the efficacy of anti-CD19 CAR-T cells in treating relapsed/refractory lymphoma patients was investigated. Prophylactic use of tocilizumab was found to reduce the incidence and severity of cytokine release syndrome, without increasing the frequency or severity of ICANS, leading to improved treatment outcomes and survival rates for patients.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Immunology
Lingyan Wang, Yue Zhang, Eden Anderson, Adam Lamble, Rimas J. Orentas
Summary: The use of CAR-T cell therapy has revolutionized the treatment of relapsed and refractory pre-B-acute lymphocytic leukemia (B-ALL) and lymphoma. However, long-term cures are still limited. This study investigated the impact of epigenetic modifiers and differentiation agents on leukemia cell lines and found that bryostatin increased CD22 expression on B-ALL cells. However, it had no effect on normal B cells and inhibited CAR-T mediated cytolysis in Burkitt lymphoma cells. These findings highlight the importance of considering disease-specific factors when using agents to enhance CAR-T killing of leukemia cells and suggest that non-CAR-mediated killing by activated T cells may play a significant role in controlling the disease.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Oncology
Penny Q. Fang, Jillian R. Gunther, Susan Y. Wu, Bouthaina S. Dabaja, Loretta J. Nastoupil, Sairah Ahmed, Sattva S. Neelapu, Chelsea C. Pinnix
Summary: CAR T-cell therapy has revolutionized the treatment approach for patients with relapsed/refractory hematologic malignancies, but there is still room for improvement in treatment toxicity and response durability. Radiation therapy can play a crucial role in combined modality treatments for some CAR T-cell therapy patients, and there are potential opportunities for future exploration of the synergy between radiation therapy and CAR T-cell treatment.
FRONTIERS IN ONCOLOGY
(2021)
Review
Oncology
Jennifer M. Logue, Julio C. Chavez
Summary: Post CAR-T failures in R/R LBCL present a new unmet need with very poor prognosis. Standard treatment options are lacking, although FDA-approved medications like polatuzumab, tafasitamab, selinexor, and loncastuximab tesirine are available, data in this setting is limited. Clinical trials with bi-specific antibodies show encouraging results with manageable toxicities, suggesting their potential in this scenario. Additional cell therapies like dual CAR-T or allogeneic products may also be considered, but challenges with logistics and further immunosuppression need to be addressed. Consolidation with stem cell transplantation could be an option for eligible patients.
CURRENT TREATMENT OPTIONS IN ONCOLOGY
(2021)
Article
Oncology
Beatrice Casadei, Lisa Argnani, Serafina Guadagnuolo, Cinzia Pellegrini, Vittorio Stefoni, Alessandro Broccoli, Laura Nanni, Alice Morigi, Ginevra Lolli, Maria Guarino, Luca Spinardi, Elisabetta Pierucci, Stefano Fanti, Michele Bartoletti, Michele Dicataldo, Elena Sabattini, Francesca Bonifazi, Pier Luigi Zinzani
Summary: Large B-cell lymphomas (LBCL) are the most common types of non-Hodgkin lymphoma, and CD19 CAR T-cell therapies have been approved for treating relapsed/refractory LBCL patients, showing a manageable safety profile and high objective response rate in the standard of care setting.
Review
Hematology
Santiago Mercadal, Carlos A. Gomez, Catherine J. Lee, Daniel R. Couriel
Summary: Chimeric antigen receptor T-cell (CAR-T) therapy targeting CD19 has significantly improved outcomes in the treatment of refractory or relapsed B-cell non-Hodgkin lymphoma (NHL). However, infections are common after CAR-T treatment, especially in patients with more than 4 prior antitumor regimens and patients aged 65 or above. Fungal infections, including fatal disseminated candidiasis and invasive pulmonary aspergillosis, carry significant morbidity and mortality. Increased fungal surveillance and anti-mold prophylaxis may be necessary in these cases. Some patients developed a antibody response following SARS-CoV-2 mRNA vaccination.
ANNALS OF HEMATOLOGY
(2023)