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Frontiers in Immunology 2021Chimeric antigen receptor T (CAR-T) cell therapy achieved extraordinary achievements results in antitumor treatments, especially against hematological malignancies,... (Review)
Review
Chimeric antigen receptor T (CAR-T) cell therapy achieved extraordinary achievements results in antitumor treatments, especially against hematological malignancies, where it leads to remarkable, long-term antineoplastic effects with higher target specificity. Nevertheless, some limitations persist in autologous CAR-T cell therapy, such as high costs, long manufacturing periods, and restricted cell sources. The development of a universal CAR-T (UCAR-T) cell therapy is an attractive breakthrough point that may overcome most of these drawbacks. Here, we review the progress and challenges in CAR-T cell therapy, especially focusing on comprehensive comparison in UCAR-T cell therapy to original CAR-T cell therapy. Furthermore, we summarize the developments and concerns about the safety and efficiency of UCAR-T cell therapy. Finally, we address other immune cells, which might be promising candidates as a complement for UCAR-T cells. Through a detailed overview, we describe the current landscape and explore the prospect of UCAR-T cell therapy.
Topics: Humans; Immunotherapy, Adoptive; Receptors, Chimeric Antigen
PubMed: 34691052
DOI: 10.3389/fimmu.2021.744823 -
Cancer Metastasis Reviews Mar 2014Breast cancer is a systemic disease with a primarily local component. Besides surgical resection and irradiation of the locoregional tumor setting, central therapeutic... (Review)
Review
Breast cancer is a systemic disease with a primarily local component. Besides surgical resection and irradiation of the locoregional tumor setting, central therapeutic aim is the elimination of disseminated micrometastatic tumor cells using cytostatic and/or hormonal treatment. Nevertheless, in the course of time a majority of patients suffer from systemic recurrence in the form of distant metastases. Intriguingly, in this connection, intratumoral cytotoxic T lymphocytes might serve as independent predictors of treatment efficacy and clinical outcome. Loss of immune balance (tumor dormancy) during intensive cross talk between T cells and tumor cells in the bone marrow microenvironment is suggested one reason for distant metastatic relapse. In this clinical context, further supportive therapies become increasingly attractive, taking immunological features of breast cancer cells into special account. The present review aims to dissect bone marrow-derived cellular antitumor immune responses and translational immunologic treatment options regarding their actual relevance to patients' clinical benefit and their future directions in breast cancer management.
Topics: Bone Marrow Cells; Breast Neoplasms; Female; Forecasting; Humans; Immunotherapy, Adoptive; Models, Immunological; Neoplasm Metastasis; T-Lymphocytes; Treatment Outcome
PubMed: 24337953
DOI: 10.1007/s10555-013-9452-6 -
Blood Oct 2023
Topics: Humans; Immunotherapy, Adoptive; B-Cell Maturation Antigen; Receptors, Chimeric Antigen; Multiple Myeloma; T-Lymphocytes
PubMed: 37471607
DOI: 10.1182/blood.2023020571 -
Cytotherapy 2007Human cytomegalovirus (HCMV) infection or reactivation is a frequent cause of morbidity and mortality in immunocompromised individuals such as transplant recipients.... (Review)
Review
Human cytomegalovirus (HCMV) infection or reactivation is a frequent cause of morbidity and mortality in immunocompromised individuals such as transplant recipients. Primary HCMV infection or reactivation of HCMV from latency is mostly asymptomatic in immunocompetent individuals and is controlled by the host's cell-mediated immune response. Healthy HCMV seropositive individuals develop high frequencies of HCMV-specific cytotoxic T lymphocytes (CTL) in the peripheral blood. Furthermore, a direct correlation between the recovery of HCMV-specific CTL responses and an improved outcome of HCMV disease could be demonstrated in immunocompromised patients. Deriving from these observations, the strategy of an adoptive transfer of HCMV-specific T cells has been developed. Protective immunity can be transferred successfully by the infusion of donor-derived HCMV-specific CD8+ cytotoxic T-cell clones or cell lines. In addition, several studies have supported the importance of antiviral effector functions of Th cells in maintaining CTL responses after adoptive transfer and their capacity to produce antiviral cytokines. Until today, a broad variety of clinical protocols for HCMV-specific immunotherapy has been published. These protocols vary regarding the isolation procedure, composition of cellular product, number of transferred cells and thus treatment efficacy. In this review, we aim to provide a comprehensive synopsis of the current standard of knowledge concerning cellular HCMV-specific immunotherapeutic approaches.
Topics: Antigen Presentation; Antigens, Viral; Cytomegalovirus; Cytomegalovirus Infections; Graft vs Host Disease; Humans; Immunocompromised Host; Immunotherapy, Adoptive; Lymphocyte Activation; Major Histocompatibility Complex; Stem Cell Transplantation; T-Lymphocyte Subsets; T-Lymphocytes, Cytotoxic
PubMed: 17917875
DOI: 10.1080/14653240701656046 -
Nature Jul 2023Engineering a patient's own T cells to selectively target and eliminate tumour cells has cured patients with untreatable haematologic cancers. These results have... (Review)
Review
Engineering a patient's own T cells to selectively target and eliminate tumour cells has cured patients with untreatable haematologic cancers. These results have energized the field to apply chimaeric antigen receptor (CAR) T therapy throughout oncology. However, evidence from clinical and preclinical studies underscores the potential of CAR T therapy beyond oncology in treating autoimmunity, chronic infections, cardiac fibrosis, senescence-associated disease and other conditions. Concurrently, the deployment of new technologies and platforms provides further opportunity for the application of CAR T therapy to noncancerous pathologies. Here we review the rationale behind CAR T therapy, current challenges faced in oncology, a synopsis of preliminary reports in noncancerous diseases, and a discussion of relevant emerging technologies. We examine potential applications for this therapy in a wide range of contexts. Last, we highlight concerns regarding specificity and safety and outline the path forward for CAR T therapy beyond cancer.
Topics: Humans; Hematologic Neoplasms; Immunotherapy, Adoptive; Neoplasms; Receptors, Chimeric Antigen; T-Lymphocytes; Autoimmune Diseases; Infections; Fibrosis; Aging; Heart Diseases
PubMed: 37495877
DOI: 10.1038/s41586-023-06243-w -
International Journal of Molecular... Jun 2020CAR-T therapy has revolutionized the treatment of select hematological malignancies, namely, acute lymphoblastic leukemia and large B-cell lymphomas [...].
CAR-T therapy has revolutionized the treatment of select hematological malignancies, namely, acute lymphoblastic leukemia and large B-cell lymphomas [...].
Topics: Animals; Antigens, Neoplasm; Disease Management; Humans; Immunotherapy, Adoptive; Receptors, Antigen, T-Cell; Receptors, Chimeric Antigen; T-Lymphocytes; Treatment Outcome
PubMed: 32560285
DOI: 10.3390/ijms21124303 -
International Journal of Clinical... Jan 2012The high risk of recurrence in post-operative hepatocellular carcinoma (HCC) highlights the need for an effective adjuvant treatment. A systematic review of randomised... (Review)
Review
The high risk of recurrence in post-operative hepatocellular carcinoma (HCC) highlights the need for an effective adjuvant treatment. A systematic review of randomised controlled trials (RCTs) was performed to evaluate the clinical efficacy of adjuvant adoptive immunotherapy (AIT) for post-operative HCC patients. Electronic (MEDLINE, EMBASE and Cochrane Library databases) and manual searches were conducted throughout May 2011 to identify RCTs evaluating postoperative AIT for patients with HCC. Methodological quality was assessed in accordance with the QUOROM statement. Four RCTs totalling 423 patients met the eligibility criteria. All RCTs reported significantly improved disease-free survival rate or reduced recurrence rate after treating with adjuvant AIT (p < 0.05). The overall survival rates of AIT group are slightly higher than those of the control group in one study. Moreover, AIT was a safe treatment, with fever as the main adverse effects. This study adds to the evidence that postoperative HCC patients treated with adjuvant AIT show an improvement in disease-free survival rate or recurrence rate.
Topics: Adjuvants, Immunologic; Carcinoma, Hepatocellular; Disease-Free Survival; Humans; Immunotherapy, Adoptive; Liver Neoplasms; Neoplasm Recurrence, Local; Postoperative Care; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 22171902
DOI: 10.1111/j.1742-1241.2011.02814.x -
Nature Reviews. Immunology May 2006Adoptive cell transfer after host preconditioning by lymphodepletion represents an important advance in cancer immunotherapy. Here, we describe how a lymphopaenic... (Review)
Review
Adoptive cell transfer after host preconditioning by lymphodepletion represents an important advance in cancer immunotherapy. Here, we describe how a lymphopaenic environment enables tumour-reactive T cells to destroy large burdens of metastatic tumour and how the state of differentiation of the adoptively transferred T cells can affect the outcome of treatment. We also discuss how the translation of these new findings might further improve the efficacy of adoptive cell transfer through the use of vaccines, haematopoietic-stem-cell transplantation, modified preconditioning regimens, and alternative methods for the generation and selection of the T cells to be transferred.
Topics: Animals; Humans; Immunotherapy, Adoptive; Neoplasms; T-Lymphocyte Subsets
PubMed: 16622476
DOI: 10.1038/nri1842 -
Nature Feb 2023The remarkable clinical activity of chimeric antigen receptor (CAR) therapies in B cell and plasma cell malignancies has validated the use of this therapeutic class for... (Review)
Review
The remarkable clinical activity of chimeric antigen receptor (CAR) therapies in B cell and plasma cell malignancies has validated the use of this therapeutic class for liquid cancers, but resistance and limited access remain as barriers to broader application. Here we review the immunobiology and design principles of current prototype CARs and present emerging platforms that are anticipated to drive future clinical advances. The field is witnessing a rapid expansion of next-generation CAR immune cell technologies designed to enhance efficacy, safety and access. Substantial progress has been made in augmenting immune cell fitness, activating endogenous immunity, arming cells to resist suppression via the tumour microenvironment and developing approaches to modulate antigen density thresholds. Increasingly sophisticated multispecific, logic-gated and regulatable CARs display the potential to overcome resistance and increase safety. Early signs of progress with stealth, virus-free and in vivo gene delivery platforms provide potential paths for reduced costs and increased access of cell therapies in the future. The continuing clinical success of CAR T cells in liquid cancers is driving the development of increasingly sophisticated immune cell therapies that are poised to translate to treatments for solid cancers and non-malignant diseases in the coming years.
Topics: Humans; Cell- and Tissue-Based Therapy; Genetic Therapy; Immunotherapy, Adoptive; Neoplasms; T-Lymphocytes; Tumor Microenvironment; B-Lymphocytes; Receptors, Chimeric Antigen
PubMed: 36813894
DOI: 10.1038/s41586-023-05707-3 -
International Journal of Biological... 2019Cancer immunotherapy by chimeric antigen receptor-modified T (CAR-T) cells has shown exhilarative clinical efficacy for hematological malignancies. Recently two CAR-T... (Review)
Review
Cancer immunotherapy by chimeric antigen receptor-modified T (CAR-T) cells has shown exhilarative clinical efficacy for hematological malignancies. Recently two CAR-T cell based therapeutics, Kymriah (Tisagenlecleucel) and Yescarta (Axicabtagene ciloleucel) approved by US FDA (US Food and Drug Administration) are now used for treatment of B cell acute lymphoblastic leukemia (B-ALL) and diffuse large B-cell lymphoma (DLBCL) respectively in the US. Despite the progresses made in treating hematological malignancies, challenges still remain for use of CAR-T cell therapy to treat solid tumors. In this landscape, most studies have primarily focused on improving CAR-T cells and overcoming the unfavorable effects of tumor microenvironment on solid tumors. To further understand the current status and trend for developing CAR-T cell based therapies for various solid tumors, this review emphasizes on CAR-T techniques, current obstacles, and strategies for application, as well as necessary companion diagnostics for treatment of solid tumors with CAR-T cells.
Topics: Cytokine Release Syndrome; Cytokines; Humans; Immunotherapy, Adoptive; Neoplasms; Treatment Outcome; Tumor Microenvironment
PubMed: 31754328
DOI: 10.7150/ijbs.34213