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Transplantation and Cellular Therapy Jan 2024The safety and efficacy of chimeric antigen receptor (CAR) T cell therapy in solid organ transplant recipients is poorly understood, given the paucity of available data... (Meta-Analysis)
Meta-Analysis
The safety and efficacy of chimeric antigen receptor (CAR) T cell therapy in solid organ transplant recipients is poorly understood, given the paucity of available data in this patient population. There is a theoretical risk of compromising transplanted organ function with CAR T cell therapy; conversely, organ transplantation-related immunosuppression can alter the function of CAR T cells. Given the prevalence of post-transplantation lymphoproliferative disease, which often can be difficult to treat with conventional chemoimmunotherapy, understanding the risks and benefits of delivering lymphoma-directed CAR T cell therapy in solid organ transplant recipients is of utmost importance. We sought to determine the efficacy of CAR T cell therapy in solid organ transplant recipients as well as the associated adverse effects, including cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), and compromised solid organ transplant function. We conducted a systematic review and meta-analysis of adult recipients of solid organ transplant who received CAR T cell therapy for non-Hodgkin lymphoma. Primary outcomes included efficacy, defined as overall response (OR), complete response (CR), progression-free survival, and overall survival, as well as rates of CRS and ICANS. Secondary outcomes included rates of transplanted organ loss, compromised organ function, and alterations to immunosuppressant regimens. After a systematic literature review and 2-reviewer screening process, we identified 10 studies suitable for descriptive analysis and 4 studies suitable for meta-analysis. Among all patients, 69% (24 of 35) achieved a response to CAR T cell therapy, and 52% (18 of 35) achieved a CR. CRS of any grade occurred in 83% (29 of 35), and CRS grade ≥3 occurred in 9% (3 of 35). Sixty percent of the patients (21 of 35) developed ICANS, and 34% (12 of 35) developed ICANS grade ≥3. The incidence of any grade 5 toxicity among all patients was 11% (4 of 35). Fourteen percent of the patients (5 of 35) experienced loss of the transplanted organ. Immunosuppressant therapy was held in 22 patients but eventually restarted in 68% of them (15 of 22). Among the studies included in the meta-analysis, the pooled OR rate was 70% (95% confidence interval [CI], 29.2% to 100%; I = 71%) and the pooled CR rate was 46% (95% CI, 25.4% to 67.8%; I = 29%). The rates of any grade CRS and grade ≥3 CRS were 88% (95% CI, 69% to 99%; I = 0%) and 5% (95% CI, 0% to 21%; I = 0%), respectively. The rates of any grade ICANS and ICANS grade ≥3 were 54% (95% CI, 9% to 96%; I = 68%) and 40% (95% CI, 3% to 85%; I = 63%), respectively. The efficacy of CAR T cell therapy in solid organ transplant recipients is comparable to that in the general population as reported in prior investigational studies, with an acceptable toxicity profile in terms of CRS, ICANS, and transplanted organ compromise. Further studies are needed to determine long-term effects on organ function, sustained response rates, and best practices peri-CAR T infusion period in this patient population.
Topics: Adult; Humans; Receptors, Chimeric Antigen; Immunotherapy, Adoptive; Lymphoma; Organ Transplantation; Adaptor Proteins, Signal Transducing; Antigens, CD19; Cytokine Release Syndrome; Immunosuppressive Agents; Cell- and Tissue-Based Therapy
PubMed: 37279856
DOI: 10.1016/j.jtct.2023.05.018 -
The AAPS Journal Apr 2021Chimeric antigen receptor (CAR) T-cell therapy is an immunotherapy that has recently become highly instrumental in the fight against life-threatening diseases. A variety...
Chimeric antigen receptor (CAR) T-cell therapy is an immunotherapy that has recently become highly instrumental in the fight against life-threatening diseases. A variety of modeling and computational simulation efforts have addressed different aspects of CAR T-cell therapy, including T-cell activation, T- and malignant cell population dynamics, therapeutic cost-effectiveness strategies, and patient survival. In this article, we present a systematic review of those efforts, including mathematical, statistical, and stochastic models employing a wide range of algorithms, from differential equations to machine learning. To the best of our knowledge, this is the first review of all such models studying CAR T-cell therapy. In this review, we provide a detailed summary of the strengths, limitations, methodology, data used, and data gap in currently published models. This information may help in designing and building better models for enhanced prediction and assessment of the benefit-risk balance associated with novel CAR T-cell therapies, as well as with the data need for building such models.
Topics: Computer Simulation; Humans; Immunotherapy, Adoptive; Machine Learning; Models, Immunological; Neoplasms; Receptors, Chimeric Antigen; Risk Assessment
PubMed: 33835308
DOI: 10.1208/s12248-021-00579-9 -
The Oncologist Mar 2022Colorectal cancer (CRC) is the second leading cause of cancer-related deaths in the US. For the vast majority of patients with advanced CRC (ie, for those in whom...
Colorectal cancer (CRC) is the second leading cause of cancer-related deaths in the US. For the vast majority of patients with advanced CRC (ie, for those in whom metastatic tumors are unresectable), treatment is palliative and typically involves chemotherapy, biologic therapy, and/or immune checkpoint inhibition. In recent years, the use of adoptive T-cell therapy (ACT), leveraging the body's own immune system to recognize and target cancer, has become increasingly popular. Unfortunately, while ACT has been successful in the treatment of hematological malignancies, it is less efficacious in advanced CRC due in part to a lack of productive immune infiltrate. This systematic review was conducted to summarize the current data for the efficacy and safety of ACT in advanced CRC. We report that ACT is well tolerated in patients with advanced CRC. Favorable survival estimates among patients with advanced CRC receiving ACT demonstrate promise for this novel treatment paradigm. However, additional stage I/II clinical trials are needed to establish the efficacy and safety of ACT in patients with CRC.
Topics: Cell- and Tissue-Based Therapy; Colorectal Neoplasms; Humans; Immunotherapy; Immunotherapy, Adoptive
PubMed: 35274719
DOI: 10.1093/oncolo/oyab038 -
Immunotherapy Sep 2017Chimeric antigen receptor modified T cells targeting CD19 and CD20 have shown activity in Phase I, II trials of patients with hematological malignancies. We conducted a... (Meta-Analysis)
Meta-Analysis Review
Chimeric antigen receptor modified T cells targeting CD19 and CD20 have shown activity in Phase I, II trials of patients with hematological malignancies. We conducted a systematic review and meta-analysis of all published clinical trials studying the role of efficacy as well as safety of CD-19 and CD-20 chimeric antigen receptor-T therapy for B-cell hematologic malignancies. A total of 16 studies with 195 patients were identified. The pooled analysis showed an overall response rate of 61% (118/195) with complete response of 42% (81/195) and partial response of 19% (37/195). Major adverse events were cytokine release syndrome 33%, neurotoxicity 33% and B-cell aplasia 54%. Collectively, the results indicate encouraging response in relapsed/refractory B lymphoma and leukemia, especially in acute lymphoblastic leukemia (ALL) patients.
Topics: Animals; Antigens, CD19; Antigens, CD20; B-Lymphocytes; Cell Count; Genetic Therapy; Hematologic Neoplasms; Humans; Immunotherapy, Adoptive; Receptors, Antigen; Recombinant Fusion Proteins; Remission Induction; T-Lymphocytes
PubMed: 28971751
DOI: 10.2217/imt-2017-0062 -
Journal of Pediatric Oncology Nursing :... 2021Children with B-precursor acute lymphoblastic leukemia and B-cell lymphoma, particularly those with relapsed or refractory disease, are increasingly enrolled on phase II...
Evidence-Based Recommendations for Nurse Monitoring and Management of Immunotherapy-Induced Cytokine Release Syndrome: A Systematic Review from the Children's Oncology Group.
Children with B-precursor acute lymphoblastic leukemia and B-cell lymphoma, particularly those with relapsed or refractory disease, are increasingly enrolled on phase II and phase III clinical trials studying immunotherapies. These therapeutic agents may be associated with a high risk of cytokine release syndrome (CRS), and nurses lack standardized guidelines for monitoring and managing patients with CRS. Six studies and one clinical practice guideline were included in this systematic review that examined the evidence of CRS following administration of chimeric antigen receptor T-cell therapy or the bi-specific T-cell engager antibody, blinatumomab. Six nursing practice recommendations (five strong, one weak) were developed based on low or very low-quality evidence: three reflect preinfusion monitoring, one focuses on monitoring during and postinfusion, and three pertain to the nurse's role in CRS management.
Topics: Child; Cytokine Release Syndrome; Humans; Immunotherapy; Immunotherapy, Adoptive; Precursor Cell Lymphoblastic Leukemia-Lymphoma
PubMed: 34460332
DOI: 10.1177/10434542211040203 -
World Journal of Gastroenterology Jul 2019Hepatocellular carcinoma (HCC) has been revealed as the second most common cause of cancer-related deaths worldwide. The introduction of cell-based immunotherapy,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Hepatocellular carcinoma (HCC) has been revealed as the second most common cause of cancer-related deaths worldwide. The introduction of cell-based immunotherapy, including dendritic cells (DCs) and cytokine-induced killer cells (CIKs), has brought HCC patients an effective benefit. However, the efficacy and necessity of cellular immunotherapy after different interventional therapy remains to be further explored.
AIM
To investigate the efficacy of cellular immunotherapy, involving DCs and CIKs, combined with different conventional treatments of HCC.
METHODS
We performed a literature search on PubMed and Web of Science up to February 15, 2019. Long-term efficacy (overall survival and recurrence) and short-term adverse effects were investigated to assess the effectiveness of immunotherapy with DCs and/or CIKs. Review Manager 5.3 was used to perform the analysis.
RESULTS
A total of 22 studies involving 3756 patients selected by eligibility inclusion criteria were forwarded for meta-analysis. Combined with the conventional clinical treatment, immunotherapy with DCs and/or CIKs was demonstrated to significantly improve overall survival at 6 mo [risk ratio (RR) = 1.07; 95% confidence interval (CI): 1.01-1.13, = 0.02], 1 year (RR = 1.12; 95%CI: 1.07-1.17, < 0.00001), 3 years (RR = 1.23; 95%CI: 1.15-1.31, < 0.00001) and 5 years (RR = 1.26; 95%CI: 1.15-1.37, < 0.00001). Recurrence rate was significantly reduced by cellular immunotherapy at 6 mo (RR = 0.50; 95%CI: 0.36-0.69, < 0.0001) and 1 year (RR = 0.82; 95%CI: 0.75-0.89, < 0.00001). Adverse effect assessment addressed that immunotherapy with DCs and/or CIKs was accepted as a safe, feasible treatment.
CONCLUSION
Combination immunotherapy with DCs, CIKs and DC/CIK with various routine treatments for HCC was evidently suggested to improve patients' prognosis by increasing overall survival and reducing cancer recurrence.
Topics: Carcinoma, Hepatocellular; Clinical Trials as Topic; Combined Modality Therapy; Cytokine-Induced Killer Cells; Dendritic Cells; Feasibility Studies; Humans; Immunotherapy, Adoptive; Liver Neoplasms; Neoplasm Recurrence, Local; Prognosis; Survival Analysis; Treatment Outcome
PubMed: 31367163
DOI: 10.3748/wjg.v25.i27.3649 -
Frontiers in Immunology 2022Different from surgery, chemical therapy, radio-therapy and target therapy, Chimeric antigen receptor-modified T (CAR-T) cells, a novel adoptive immunotherapy strategy,...
Different from surgery, chemical therapy, radio-therapy and target therapy, Chimeric antigen receptor-modified T (CAR-T) cells, a novel adoptive immunotherapy strategy, have been used successfully against both hematological tumors and solid tumors. Although several problems have reduced engineered CAR-T cell therapeutic outcomes in clinical trials for the treatment of thoracic malignancies, including the lack of specific antigens, an immunosuppressive tumor microenvironment, a low level of CAR-T cell infiltration into tumor tissues, off-target toxicity, and other safety issues, CAR-T cell treatment is still full of bright future. In this review, we outline the basic structure and characteristics of CAR-T cells among different period, summarize the common tumor-associated antigens in clinical trials of CAR-T cell therapy for thoracic malignancies, and point out the current challenges and new strategies, aiming to provide new ideas and approaches for preclinical experiments and clinical trials of CAR-T cell therapy for thoracic malignancies.
Topics: Humans; Immunotherapy; Immunotherapy, Adoptive; Receptors, Chimeric Antigen; T-Lymphocytes; Thoracic Neoplasms; Tumor Microenvironment
PubMed: 35911706
DOI: 10.3389/fimmu.2022.871661 -
Clinical Nutrition ESPEN Dec 2021Chimeric Antigen Receptor (CAR) T cell therapy is a novel adoptive immunotherapy that is revolutionising the treatment of haematological malignancies and solid tumours....
BACKGROUND & AIMS
Chimeric Antigen Receptor (CAR) T cell therapy is a novel adoptive immunotherapy that is revolutionising the treatment of haematological malignancies and solid tumours. Maintaining a patient's nutritional status and implementing nutrition support interventions have been shown to improve certain patient outcomes in standard anti-cancer therapies; however, guidance for nutrition support interventions in CAR T cell therapy are lacking. The primary aim of this review was to determine the impact of nutrition support interventions on patient-centred outcomes for adult CAR T cell therapy haematology and oncology patients. The patient-centred outcomes of interest included nutritional status and dietary intake, morbidity, functional status, and mortality. Our secondary aim was to describe the nutrition implications that have been acknowledged (but not fully evaluated) in CAR T cell therapy, and to guide future research and practice.
METHODS
Four electronic databases (CENTRAL, Embase, MEDLINE and CINAHL) were searched to January 2021, with additional records identified through handsearching and snowballing. Studies considered eligible for inclusion were randomised control trials (RCT), quasi-RCTs, cohort and observational studies, assessing nutrition support interventions (oral, enteral and/or parenteral) in adult haematology and oncology patients receiving CAR T cell therapy or adoptive immunotherapy. No publication status, year or language restrictions were applied.
RESULTS
Two authors reviewed the title and abstracts of 1181 retrieved records; however no studies were eligible for inclusion in this systematic review.
CONCLUSIONS
We are currently unable to identify if there is an association between nutrition support interventions and outcomes in CAR T cell therapy for adults with haematological malignancies or solid tumours. Lower quality clinical studies and animal models were identified that permitted us to qualitatively describe the risks for poor nutritional status in this population. This empty review confirms the need for research into the potential impact of nutrition support in CAR T cell therapy, including well-designed RCTs.
Topics: Hematology; Humans; Immunotherapy, Adoptive; Neoplasms; Nutritional Support; Parenteral Nutrition; Randomized Controlled Trials as Topic
PubMed: 34857249
DOI: 10.1016/j.clnesp.2021.10.015 -
International Immunopharmacology Dec 2021Hepatocellular carcinoma (HCC) is the most common liver neoplasm with high morbidity and mortality. Tumor immunotherapy might be promising adjuvant therapy for HCC after...
BACKGROUND
Hepatocellular carcinoma (HCC) is the most common liver neoplasm with high morbidity and mortality. Tumor immunotherapy might be promising adjuvant therapy for HCC after surgery. To better develop HCC immunotherapy, comprehensive understanding of cell-cell interactions between immune effector cells and HCC cells remains crucial.
AIM
To review the existing studies to summarize the cell-cell interactions between major immune effector cells and HCC cells providing new data for HCC immunotherapy.
METHODS
A systematic review was conducted by searching PubMed database covering all papers published in recent five years up to January 2020. The guidelines of the preferred reporting items for systematic reviews were firmly followed.
RESULTS
There are 9 studies researching the interactions between CD8 T lymphocytes and HCC cells and 22 studies researching that between natural killer (NK) cells and HCC cells. Among the 9 studies, 6 studies reported that CD8 T lymphocytes showed cytotoxicity towards HCC cells while 3 studies found CD8 T lymphocytes were impaired by HCC cells. Among the 22 studies, 20 studies presented that NK cells could inhibit HCC cells. Two studies were found to report NK cell dysfunction in HCC.
CONCLUSION
Based on the systematic analysis, we concluded that CD8 T lymphocytes and NK cells can inhibit HCC cells. While in turn, HCC cells can also result in the dysfunction of those effector cells through various mechanisms. Organoids and direct contact cell co-culture with primary HCC cells and TILs should be the most innovative way to investigate the interactions and develop novel immunotherapy.
Topics: Carcinoma, Hepatocellular; Cell Communication; Chemotherapy, Adjuvant; Coculture Techniques; Hepatectomy; Humans; Immune Checkpoint Inhibitors; Immunotherapy; Immunotherapy, Adoptive; Killer Cells, Natural; Liver; Liver Neoplasms; Primary Cell Culture; T-Lymphocytes, Cytotoxic; Tumor Cells, Cultured; Tumor Microenvironment
PubMed: 34673334
DOI: 10.1016/j.intimp.2021.108220 -
Immunotherapy Mar 2021The aim was to evaluate the efficacy and safety of chimeric antigen receptor T (CAR-T) cell in B-cell non-Hodgkin lymphoma (B-NHL). A meta-analysis was conducted using... (Meta-Analysis)
Meta-Analysis
The aim was to evaluate the efficacy and safety of chimeric antigen receptor T (CAR-T) cell in B-cell non-Hodgkin lymphoma (B-NHL). A meta-analysis was conducted using eligible clinical trials, which were obtained from electronic medical literature databases. A total of 24 clinical trials with 590 patients were included. The best overall response rate was 66% and complete remission rate was 46%. The incidence rates of cytokine-release syndrome and neurotoxicity (grade ≥ 3) were 9 and 5%, respectively. The various clinical factors were analyzed. Autogenic CAR-T cell may lead to improved efficacy than allogeneic CAR-T cell. CD20 CAR-T cell may show increased efficacy than CD19 CAR-T cell. CAR-T immunotherapy has remarkable efficacy and low toxicity in relapsed/refractory B-NHL.
Topics: Adult; Aged; Aged, 80 and over; Antigens, CD19; Antigens, CD20; Clinical Trials as Topic; Cytokine Release Syndrome; Female; Humans; Immunotherapy, Adoptive; Lymphoma, B-Cell; Male; Middle Aged; Neurotoxicity Syndromes; Receptors, Antigen, T-Cell; Receptors, Chimeric Antigen; T-Lymphocytes; Treatment Outcome; Young Adult
PubMed: 33406914
DOI: 10.2217/imt-2020-0221