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Advances in Immunology 2016Recent developments have demonstrated that immunotherapies are capable of achieving durable antitumor responses in patients with metastatic cancer. One modality that has... (Review)
Review
Recent developments have demonstrated that immunotherapies are capable of achieving durable antitumor responses in patients with metastatic cancer. One modality that has been able to induce durable complete regressions in patients with melanoma has been adoptive cell therapy (ACT). This has slowly been expanded to other cancer types using new approaches such as genetically engineered T-cells and other methods of antigen targeting. It now appears that immune targeting of mutated "neoantigens" plays a major role in successful ACT, as well as in other immunotherapies such as checkpoint inhibitors. This realization presents not only new challenges to ACT but also new opportunities in that all tumors now may have potential antigens to attack that can be revealed by tumor genomic sequencing. There are a variety of exciting approaches to translate these new findings into clinical trials applying ACT to the majority of cancer types.
Topics: Animals; Antigens, Neoplasm; Cell Cycle Checkpoints; Cell Engineering; Humans; Immunotherapy, Adoptive; Lymphocytes, Tumor-Infiltrating; Mice; Mutation; Neoplasms; T-Lymphocytes
PubMed: 26923004
DOI: 10.1016/bs.ai.2015.12.006 -
Chinese Clinical Oncology Apr 2017Adoptive cell therapy (ACT) has been developed in cancer treatment by transferring/infusing immune cells into cancer patients, which are able to recognize, target, and... (Review)
Review
Adoptive cell therapy (ACT) has been developed in cancer treatment by transferring/infusing immune cells into cancer patients, which are able to recognize, target, and destroy tumor cells. Recently, sipuleucel-T and genetically-modified T cells expressing chimeric antigen receptors (CAR) show a great potential to control metastatic castration-resistant prostate cancer and hematologic malignancies in clinic. This review summarized some of the major evidence-based ACT and the challenges to improve cell quality and reduce the side effects in the field. This review also provided future research directions to make sure ACT widely available in clinic.
Topics: Cancer Vaccines; Humans; Immunotherapy, Adoptive; Male; Neoplasms; Prostatic Neoplasms, Castration-Resistant; T-Lymphocytes; Tissue Extracts
PubMed: 28482671
DOI: 10.21037/cco.2017.02.07 -
Journal of Experimental & Clinical... Aug 2021Cancer immunotherapy has gained attention as the supreme therapeutic modality for the treatment of various malignancies. Adoptive T-cell therapy (ACT) is one of the most... (Review)
Review
Cancer immunotherapy has gained attention as the supreme therapeutic modality for the treatment of various malignancies. Adoptive T-cell therapy (ACT) is one of the most distinctive modalities of this therapeutic approach, which seeks to harness the potential of combating cancer cells by using autologous or allogenic tumor-specific T-cells. However, a plethora of circumstances must be optimized to produce functional, durable, and efficient T-cells. Recently, the potential of ACT has been further realized by the introduction of novel gene-editing platforms such as the CRISPR/Cas9 system; this technique has been utilized to create T-cells furnished with recombinant T-cell receptor (TCR) or chimeric antigen receptor (CAR) that have precise tumor antigen recognition, minimal side effects and treatment-related toxicities, robust proliferation and cytotoxicity, and nominal exhaustion. Here, we aim to review and categorize the recent breakthroughs of genetically modified TCR/CAR T-cells through CRISPR/Cas9 technology and address the pearls and pitfalls of each method. In addition, we investigate the latest ongoing clinical trials that are applying CRISPR-associated TCR/CAR T-cells for the treatment of cancers.
Topics: CRISPR-Cas Systems; Gene Editing; Humans; Immunotherapy, Adoptive; Neoplasms; Receptors, Antigen, T-Cell; T-Lymphocytes
PubMed: 34446084
DOI: 10.1186/s13046-021-02076-5 -
Frontiers in Immunology 2023The development and growth of tumors remains an important and ongoing threat to human life around the world. While advanced therapeutic strategies such as immune... (Review)
Review
The development and growth of tumors remains an important and ongoing threat to human life around the world. While advanced therapeutic strategies such as immune checkpoint therapy and CAR-T have achieved astonishing progress in the treatment of both solid and hematological malignancies, the malignant initiation and progression of cancer remains a controversial issue, and further research is urgently required. The experimental animal model not only has great advantages in simulating the occurrence, development, and malignant transformation mechanisms of tumors, but also can be used to evaluate the therapeutic effects of a diverse array of clinical interventions, gradually becoming an indispensable method for cancer research. In this paper, we have reviewed recent research progress in relation to mouse and rat models, focusing on spontaneous, induced, transgenic, and transplantable tumor models, to help guide the future study of malignant mechanisms and tumor prevention.
Topics: Humans; Animals; Mice; Rats; Neoplasms; Immunotherapy, Adoptive; Hematologic Neoplasms; Disease Models, Animal; Animals, Genetically Modified
PubMed: 36969176
DOI: 10.3389/fimmu.2023.1095388 -
Frontiers in Immunology 2023Chimeric antigen receptor (CAR) T therapies are being developed for acute myeloid leukemia (AML) on the basis of the results obtained for other haematological... (Review)
Review
Chimeric antigen receptor (CAR) T therapies are being developed for acute myeloid leukemia (AML) on the basis of the results obtained for other haematological malignancies and the need of new treatments for relapsed and refractory AML. The biggest challenge of CART therapy for AML is to identify a specific target antigen, since antigens expressed in AML cells are usually shared with healthy haematopoietic stem cells (HSC). The concomitant expression of the target antigen on both tumour and HSC may lead to on-target/off-tumour toxicity. In this review, we guide researchers to design, develop, and translate to the clinic CART therapies for the treatment of AML. Specifically, we describe what issues have to be considered to design these therapies; what and assays can be used to prove their efficacy and safety; and what expertise and facilities are needed to treat and manage patients at the hospital.
Topics: Humans; T-Lymphocytes; Leukemia, Myeloid, Acute; Immunotherapy, Adoptive; Hematopoietic Stem Cells
PubMed: 38098489
DOI: 10.3389/fimmu.2023.1260470 -
Cancer Immunology, Immunotherapy : CII Jun 2016Immunotherapy is one of the most promising and innovative approaches to treat cancer, viral infections, and other immune-modulated diseases. Adoptive immunotherapy using... (Review)
Review
Immunotherapy is one of the most promising and innovative approaches to treat cancer, viral infections, and other immune-modulated diseases. Adoptive immunotherapy using gene-modified T cells is an exciting and rapidly evolving field. Exploiting knowledge of basic T cell biology and immune cell receptor function has fostered innovative approaches to modify immune cell function. Highly translatable clinical technologies have been developed to redirect T cell specificity by introducing designed receptors. The ability to engineer T cells to manifest desired phenotypes and functions is now a thrilling reality. In this review, we focus on outlining different varieties of genetically engineered T cells, their respective advantages and disadvantages as tools for immunotherapy, and their promise and drawbacks in the clinic.
Topics: Animals; Antigens, Neoplasm; Clinical Trials as Topic; Cytokines; Genetic Engineering; Humans; Immunotherapy; Immunotherapy, Adoptive; Mice; Neoplasms; Receptors, Antigen, T-Cell; Recombinant Fusion Proteins; T-Lymphocytes; Treatment Outcome
PubMed: 27138532
DOI: 10.1007/s00262-016-1842-5 -
Expert Review of Pharmacoeconomics &... Dec 2019: Diffuse large B-cell lymphoma (DLBCL) is the most common non-Hodgkin lymphoma and is a clinically heterogeneous disease. Treatment pathways for DLBCL are diverse and... (Review)
Review
: Diffuse large B-cell lymphoma (DLBCL) is the most common non-Hodgkin lymphoma and is a clinically heterogeneous disease. Treatment pathways for DLBCL are diverse and integrate established and novel therapies.: We review the cost burden of DLBCL and the cost-effectiveness of DLBCL management including precision and cellular medicine. We utilized Medical Subject Heading (MeSH) terms and keywords to search the National Library of Medicine online MEDLINE database (PubMed) for articles related to cost, cost burden, and cost-of-illness of DLBCL and cost-effectiveness of DLBCL management strategies published in English as of June 2019.: Available and developing DLBCL therapies offer improved outcomes and often curative treatment at considerable financial expense, and the total cost burden for DLBCL management is substantial for patients and the healthcare system. In the era of personalized medicine, CAR T cells and targeted therapies provide exciting avenues for current and future DLBCL care and can further increase treatment cost. Determinations of cost and cost-effectiveness in DLBCL treatment pathways should continue to guide care providers and systems in identifying cost reduction strategies to provide appropriate therapies to the greatest number of patients in treating DLBCL.
Topics: Cost of Illness; Cost-Benefit Analysis; Humans; Immunotherapy, Adoptive; Lymphoma, Large B-Cell, Diffuse; Molecular Targeted Therapy; Precision Medicine
PubMed: 31623476
DOI: 10.1080/14737167.2019.1680288 -
Biology of Blood and Marrow... Mar 2019Adoptive immunotherapy has shown efficacy in patients with relapsed/refractory acute myelogenous leukemia (AML). We conducted a prospective evaluation of cord blood...
Adoptive immunotherapy has shown efficacy in patients with relapsed/refractory acute myelogenous leukemia (AML). We conducted a prospective evaluation of cord blood (CB)-based adoptive cell therapy following salvage chemotherapy in patients with AML or myelodysplastic syndrome (MDS) and describe the safety and early outcomes of this approach. To enhance the antileukemic effect, we selected CB units (CBUs) with a shared inherited paternal antigen (IPA) and/or noninherited maternal antigen (NIMA) match with the recipients. Furthermore, the CBUs had total nucleated cell (TNC) dose <2.5 × 10/kg and were at least 4/6 HLA-matched with the patients; a higher allele-level match was preferred. Heavily pretreated adult patients with AML/MDS were enrolled. CBU searches were performed for 50 patients. CBUs with shared IPA targets were identified for all, and CBUs with NIMA matches were found for 80%. Twenty-one patients underwent treatment (AML, primary induction failure, n = 8; refractory relapse, n = 10, including 7 recipients of previous allogeneic HSCT; blast crisis chronic myelogenous leukemia, n = 1; MDS, n = 2). Most received combination chemotherapy; those not fit for intensive treatment received a hypomethylating agent. Response was defined as <10% residual blasts in hypocellular bone marrow at approximately 2 weeks after treatment. Ten of the 19 evaluable patients responded, including 5 of the 7 recipients of previous transplant. Response was seen in 4 of 4 patients with full CBU-derived chimerism, 2 of 2 of those with partial, low-level chimerism and 4 of 12 of the recipients with no detectable CBU chimerism. The most common adverse events were infections (bacterial, n = 5; viral, n = 2; fungal, n = 5). Grade IV acute graft-versus-host disease (GVHD) developed in 2 patients with full CBU chimerism; 2 other patients had grade 1 skin GVHD. A total of 11 patients died, 7 from disease recurrence and 4 from infections (1 early death; the other 3 in remission at the time of death). Overall, 12 patients proceeded to allogeneic HSCT; of those, 7 had responded to treatment, 3 had not (and had received additional therapy), and 2 had persistent minimal residual disease. In conclusion, the use of CB as adoptive immunotherapy in combination with salvage chemotherapy for patients with refractory AML/MDS is feasible, can induce disease control, can serve as a bridge to allogeneic HSCT, and has an acceptable incidence of adverse events. Alloreactivity was enhanced through the selection of CBUs targeting a shared IPA and/or NIMA match with the patients. CBUs with lower cell doses, already available in the CB bank and unlikely to be adequate grafts for adult transplants, can be used for cell therapy within a short time frame.
Topics: Adolescent; Adult; Chimerism; Female; Fetal Blood; Graft vs Host Disease; Humans; Immunotherapy, Adoptive; Infections; Leukemia, Myeloid, Acute; Male; Middle Aged; Myelodysplastic Syndromes; Prospective Studies; Salvage Therapy; Treatment Outcome
PubMed: 30414955
DOI: 10.1016/j.bbmt.2018.11.002 -
International Journal of Molecular... Mar 2023After seeing a dramatic increase in the development and use of immunotherapy and precision medicine over the past few decades, oncological care now embraces the start of... (Review)
Review
After seeing a dramatic increase in the development and use of immunotherapy and precision medicine over the past few decades, oncological care now embraces the start of the adoptive cell therapy (ACT) era. This impulse towards a new treatment paradigm has been led by chimeric antigen receptor (CAR) T cells, the only type of ACT medicinal product to be commercialized so far. Brought about by an ever-growing understanding of cellular engineering, CAR T cells are T lymphocytes genetically modified with an appropriate DNA construct, which endows them with expression of a CAR, a fusion protein between a ligand-specific recognition domain, often an antibody-like structure, and the activating signaling domain of the T cell receptor. Through this genetic enhancement, CAR T cells are engineered from a cancer patient's own lymphocytes to better target and kill their cancer cells, and the current amassed data on clinical outcomes point to a stream of bright developments in the near future. Herein, from concept design and present-day manufacturing techniques to pressing hurdles and bright discoveries around the corner, we review and thoroughly describe the state of the art in CAR T cell therapy.
Topics: Humans; Immunotherapy, Adoptive; Receptors, Antigen, T-Cell; T-Lymphocytes; Neoplasms
PubMed: 37047272
DOI: 10.3390/ijms24076300 -
Frontiers in Immunology 2021Chimeric antigen receptor (CAR) T-cell immunotherapy refers to an adoptive immunotherapy that has rapidly developed in recent years. It is a novel type of treatment that... (Review)
Review
Chimeric antigen receptor (CAR) T-cell immunotherapy refers to an adoptive immunotherapy that has rapidly developed in recent years. It is a novel type of treatment that enables T cells to express specific CARs on their surface, then returns these T cells to tumor patients to kill the corresponding tumor cells. Significant strides in CAR-T cell immunotherapy against hematologic malignancies have elicited research interest among scholars in the treatment of solid tumors. Nonetheless, in contrast with the efficacy of CAR-T cell immunotherapy in the treatment of hematologic malignancies, its general efficacy against solid tumors is insignificant. This has been attributed to the complex biological characteristics of solid tumors. CAR-T cells play a better role in solid tumors, for instance by addressing obstacles including the lack of specific targets, inhibition of tumor microenvironment (TME), homing barriers of CAR-T cells, differentiation and depletion of CAR-T cells, inhibition of immune checkpoints, trogocytosis of CAR-T cells, tumor antigen heterogeneity, etc. This paper reviews the obstacles influencing the efficacy of CAR-T cell immunotherapy in solid tumors, their mechanism, and coping strategies, as well as economic restriction of CAR-T cell immunotherapy and its solutions. It aims to provide some references for researchers to better overcome the obstacles that affect the efficacy of CAR-T cells in solid tumors.
Topics: Animals; Cost-Benefit Analysis; Cytotoxicity, Immunologic; Health Care Costs; Health Services Accessibility; Humans; Immunotherapy, Adoptive; Neoplasms; Receptors, Chimeric Antigen; T-Lymphocytes; Treatment Outcome; Tumor Microenvironment
PubMed: 34093592
DOI: 10.3389/fimmu.2021.687822