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Cells, Tissues, Organs 2023The past decade has witnessed significant advances in cancer immunotherapy, particularly through the adoptive transfer of engineered T cells in treating advanced... (Review)
Review
The past decade has witnessed significant advances in cancer immunotherapy, particularly through the adoptive transfer of engineered T cells in treating advanced leukemias and lymphomas. Despite these excitements, challenges remain with scale, cost, and ensuring quality control of engineered immune cells, including chimeric antigen receptor T, natural killer cells, and macrophages. The advent of human pluripotent stem cells (hPSCs), including human embryonic stem cells and induced pluripotent stem cells, has transformed immunotherapy by providing a scalable, off-the-shelf source of any desired immune cells for basic research, translational studies, and clinical interventions. The tractability of hPSCs for gene editing could also generate homogenous, universal cellular products with custom functionality for individual or combinatory therapeutic applications. This review will explore various immune cell types whose directed differentiation from hPSCs has been achieved and recently adapted for translational immunotherapy and feature forward-looking bioengineering techniques shaping the future of the stem cell field.
Topics: Humans; Immunotherapy, Adoptive; Pluripotent Stem Cells; Killer Cells, Natural; T-Lymphocytes; Induced Pluripotent Stem Cells; Immunotherapy; Neoplasms
PubMed: 36599319
DOI: 10.1159/000528838 -
Expert Opinion on Biological Therapy Apr 2015Conventional treatments reached an unsatisfactory therapeutic plateau in the treatment of advanced unresectable bone and soft tissue sarcomas that remain an unsolved... (Review)
Review
INTRODUCTION
Conventional treatments reached an unsatisfactory therapeutic plateau in the treatment of advanced unresectable bone and soft tissue sarcomas that remain an unsolved medical need. Several evidences support the concept that adoptive immunotherapy may effectively integrate within the complex and multidisciplinary treatment of sarcomas.
AREAS COVERED
In this work we reviewed adoptive immunotherapy strategies that have been explored in sarcoma settings, with specific focus on issues related to their clinic transferability. We schematically divided approaches based on T lymphocytes specific for MHC-restricted tumor-associated antigens or relying on MHC-independent immune effectors such as natural killer (NK), cytokine-induced killer (CIK) or γδ T cells.
EXPERT OPINION
Preclinical findings and initial clinical reports showed the potentialities and drawbacks of different adoptive immunotherapy strategies. The expansion of tumor infiltrating lymphocytes is difficult to be reproduced outside melanoma. Genetically redirected T cells appear to be a promising option and initial reports are encouraging against patients with sarcomas. Adoptive immunotherapy with MHC-unrestricted effectors such as NK, CIK or γδ T cells has recently shown great preclinical potential in sarcoma setting and biologic features that may favor clinical transferability. Combination of different immunotherapy approaches and integration with conventional treatments appear to be key issues for successful designing of next clinical trials.
Topics: Animals; Cytokine-Induced Killer Cells; Cytokines; Humans; Immunotherapy, Adoptive; Sarcoma; T-Lymphocytes
PubMed: 25516119
DOI: 10.1517/14712598.2015.987121 -
Immunological Reviews Jan 2014Recent clinical success has underscored the potential for immunotherapy based on the adoptive cell transfer (ACT) of engineered T lymphocytes to mediate dramatic,... (Review)
Review
Recent clinical success has underscored the potential for immunotherapy based on the adoptive cell transfer (ACT) of engineered T lymphocytes to mediate dramatic, potent, and durable clinical responses. This success has led to the broader evaluation of engineered T-lymphocyte-based adoptive cell therapy to treat a broad range of malignancies. In this review, we summarize concepts, successes, and challenges for the broader development of this promising field, focusing principally on lessons gleaned from immunological principles and clinical thought. We present ACT in the context of integrating T-cell and tumor biology and the broader systemic immune response.
Topics: Adoptive Transfer; Animals; History, 20th Century; History, 21st Century; Humans; Immunotherapy, Adoptive; Neoplasms; T-Lymphocyte Subsets
PubMed: 24329787
DOI: 10.1111/imr.12136 -
Current Opinion in Oncology Nov 1997Some of the most dramatic advances in the treatment of cancer have used the immune system in combination with conventional or transplantation chemotherapy. Adoptive... (Review)
Review
Some of the most dramatic advances in the treatment of cancer have used the immune system in combination with conventional or transplantation chemotherapy. Adoptive immunotherapy has been used for relapses after allogeneic bone marrow transplantation, and it has been particularly effective for chronic myeloid leukemia. Adoptive immunotherapy also has been used for Epstein-Barr virus-related lymphomas developing after allogeneic marrow transplantations. Cellular therapy, including the infusion of tumor-reactive immune cells, has been used to mediate response of established solid tumors. This has been used for therapeutic benefit for renal cell carcinoma, melanoma, lung cancer, and breast cancer. Current research is focusing on reducing the toxicity of these approaches as well as further defining the appropriate target tissue.
Topics: Animals; Humans; Immunotherapy, Adoptive; Neoplasms; Neoplasms, Experimental
PubMed: 9370080
DOI: 10.1097/00001622-199711000-00014 -
Blood Cancer Journal Apr 2021Chimeric antigen receptor (CAR)-T cell therapy is a revolutionary new pillar in cancer treatment. Although treatment with CAR-T cells has produced remarkable clinical... (Review)
Review
Chimeric antigen receptor (CAR)-T cell therapy is a revolutionary new pillar in cancer treatment. Although treatment with CAR-T cells has produced remarkable clinical responses with certain subsets of B cell leukemia or lymphoma, many challenges limit the therapeutic efficacy of CAR-T cells in solid tumors and hematological malignancies. Barriers to effective CAR-T cell therapy include severe life-threatening toxicities, modest anti-tumor activity, antigen escape, restricted trafficking, and limited tumor infiltration. In addition, the host and tumor microenvironment interactions with CAR-T cells critically alter CAR-T cell function. Furthermore, a complex workforce is required to develop and implement these treatments. In order to overcome these significant challenges, innovative strategies and approaches to engineer more powerful CAR-T cells with improved anti-tumor activity and decreased toxicity are necessary. In this review, we discuss recent innovations in CAR-T cell engineering to improve clinical efficacy in both hematological malignancy and solid tumors and strategies to overcome limitations of CAR-T cell therapy in both hematological malignancy and solid tumors.
Topics: Animals; Hematologic Neoplasms; Humans; Immunotherapy, Adoptive; Neoplasms; Receptors, Chimeric Antigen; T-Lymphocytes; Tumor Microenvironment
PubMed: 33824268
DOI: 10.1038/s41408-021-00459-7 -
Cancer Treatment Reviews Nov 2021Multiple systemic treatments are currently available for advanced cancers of the digestive tract, but none of them is curative. Adoptive T-cell immunotherapy refers to... (Review)
Review
Multiple systemic treatments are currently available for advanced cancers of the digestive tract, but none of them is curative. Adoptive T-cell immunotherapy refers to the extraction, modification and re-infusion of autologous or allogenic T lymphocytes for therapeutic purposes. A number of clinical trials have investigated either non-engineered T cells (i.e., lymphokine-activated killer cells, cytokine induced killer cells, or tumor-infiltrating lymphocytes) or engineered T cells (T cell receptor-redirected T cells or chimeric antigen receptor T cells) in patients with digestive tract malignancies over the past two decades, with variable degrees of success. While the majority of completed trials have been primarily aimed at assessing the safety of T-cell transfer strategies, a new generation of studies is being designed to formally evaluate the antitumor potential of adoptive T-cell immunotherapy in both the metastatic and adjuvant settings. In this review, we provide an overview of completed and ongoing clinical trials of passive T-cell immunotherapy in patients with cancers of the digestive tract, focusing on present obstacles and future strategies for achieving potential success.
Topics: Digestive System Neoplasms; Humans; Immunotherapy, Adoptive; Receptors, Chimeric Antigen
PubMed: 34525422
DOI: 10.1016/j.ctrv.2021.102288 -
Technology in Cancer Research &... 2023Adoptive cell immunotherapy (ACT) is an innovative promising treatment for tumors. ACT is characterized by the infusion of active anti-tumor immune cells (specific and... (Review)
Review
Adoptive cell immunotherapy (ACT) is an innovative promising treatment for tumors. ACT is characterized by the infusion of active anti-tumor immune cells (specific and non-specific) into patients to kill tumor cells either directly or indirectly by stimulating the body's immune system. The patient's (autologous) or a donor's (allogeneic) immune cells are used to improve immune function. Chimeric antigen receptor (CAR) T cells (CAR-T) is a type of ACT that has gained attention. T cells from the peripheral blood are genetically engineered to express CARs that rapidly proliferate and specifically recognize target antigens to exert its anti-tumor effects. Clinical application of CAR-T therapy for hematological tumors has shown good results, but adverse reactions and recurrence limit its applicability. Tumor infiltrating lymphocyte (TIL) therapy is effective for solid tumors. TIL therapy exhibits T cell receptor (TCR) clonality, superior tumor homing ability, and low targeted toxicity, but its successful application is limited to a number of tumors. Regardless, TIL and CAR-T therapies are effective for treating cancer. Additionally, CAR-natural killer (NK), CAR-macrophages (M), and TCR-T therapies are currently being researched. In this review, we highlight the current developments and limitations of several types of ACT.
Topics: Humans; Immunotherapy, Adoptive; Receptors, Chimeric Antigen; T-Lymphocytes; Receptors, Antigen, T-Cell; Neoplasms; Immunotherapy
PubMed: 38037341
DOI: 10.1177/15330338231204198 -
Molecular Therapy : the Journal of the... Apr 2019Adoptive T cell therapy is a form of cellular therapy that utilizes human immune cells, often empowered by the expression of recombinant proteins, to attack selected... (Review)
Review
Adoptive T cell therapy is a form of cellular therapy that utilizes human immune cells, often empowered by the expression of recombinant proteins, to attack selected targets present on tumor or infected cells. T cell-based immunotherapy has been progressing over the past several decades, and reached a milestone with the recent US Food and Drug Administration (FDA) approval of chimeric antigen receptor T cell therapy for relapsed and refractory leukemia and lymphoma. Although most studies have used viral vectors, a growing number of researchers have come to appreciate in vitro-transcribed (IVT) mRNA for the development, testing, and application of T cell-based immunotherapeutics. IVT mRNA offers inherent safety features, highly efficient recombinant protein translation, and the ability to control pharmacokinetic properties of the therapy. In this review, we discuss the history of IVT mRNA in adoptive T cell therapy, from tumor-infiltrating lymphocytes and T cell receptor-based therapies to chimeric antigen receptor therapy and gene-editing techniques, as well as prior and ongoing clinical trials.
Topics: Animals; Cell- and Tissue-Based Therapy; Gene Editing; Genetic Vectors; Humans; Immunotherapy, Adoptive; In Vitro Techniques; Lymphocytes, Tumor-Infiltrating; Mice; Neoplasms; RNA, Messenger; Receptors, Antigen, T-Cell; Receptors, Chimeric Antigen; T-Lymphocytes; Transcription, Genetic
PubMed: 30819612
DOI: 10.1016/j.ymthe.2019.01.018 -
Immunological Reviews Jan 2014
Topics: Humans; Immunotherapy, Adoptive; Neoplasms
PubMed: 24329785
DOI: 10.1111/imr.12145 -
Frontiers in Immunology 2020Adoptive cell therapy (ACT) is a kind of immunotherapy in which T cells are genetically modified to express a chimeric antigen receptor (CAR) or T cell receptor (TCR),... (Review)
Review
Adoptive cell therapy (ACT) is a kind of immunotherapy in which T cells are genetically modified to express a chimeric antigen receptor (CAR) or T cell receptor (TCR), and ACT has made a great difference in treating multiple types of tumors. ACT is not perfect, and it can be followed by severe side effects, which hampers the application of ACT in clinical trials. One of the most promising methods to minimize side effects is to endow adoptive T cells with the ability to target neoantigens, which are specific to tumor cells. With the development of antigen screening technologies, more methods can be applied to discover neoantigens in cancer cells, such as whole-exome sequencing combined with mass spectrometry, neoantigen screening through an inventory-shared neoantigen peptide library, and neoantigen discovery via trogocytosis. In this review, we focus on the side effects of existing antigens and their solutions, illustrate the strategies of finding neoantigens in CAR-T and TCR-T therapies through methods reported by other researchers, and summarize the clinical behavior of these neoantigens.
Topics: Animals; Antigens, Neoplasm; Cell- and Tissue-Based Therapy; Disease Models, Animal; Humans; Immunotherapy, Adoptive; Lymphocytes, Tumor-Infiltrating; Mass Spectrometry; Mice; Neoplasms; Receptors, Chimeric Antigen; Exome Sequencing
PubMed: 32194541
DOI: 10.3389/fimmu.2020.00176