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Immunotherapy Jan 2017The immune system is a potent inhibitor of tumor growth with curative potential, constituting in many eyes the future of antineoplastic therapy. Adoptive cell therapy... (Review)
Review
The immune system is a potent inhibitor of tumor growth with curative potential, constituting in many eyes the future of antineoplastic therapy. Adoptive cell therapy (ACT) is a form of immunotherapy in which autologous cancer-cognate lymphocytes are expanded and modified ex vivo and re-infused to combat the tumor. This review follows the evolvement of ACT and treatment protocols, focusing on unresolved dilemmas regarding this treatment while providing evidence for its effectiveness in refractory patients. Future directions of ACT are discussed, in particular with regard to genetic engineering of autologous cells, and the role of ACT in the era of checkpoint inhibitors is addressed.
Topics: Animals; Antibodies, Monoclonal; Antigens, Neoplasm; Costimulatory and Inhibitory T-Cell Receptors; Genetic Engineering; Humans; Immunotherapy, Adoptive; Lymphocytes, Tumor-Infiltrating; Neoplasms; Receptors, Antigen, T-Cell
PubMed: 28128715
DOI: 10.2217/imt-2016-0112 -
[Rinsho Ketsueki] the Japanese Journal... Oct 2014
Review
Topics: Animals; Clinical Trials as Topic; Genes, T-Cell Receptor; Genetic Techniques; Hematologic Neoplasms; Humans; Immunotherapy, Adoptive; Mice; Receptors, Antigen, T-Cell; T-Lymphocytes
PubMed: 25297783
DOI: No ID Found -
Frontiers in Immunology 2021Recently, many reports were published supporting the clinical use of adoptively transferred natural killer (NK) cells as a therapeutic tool against cancer, including...
Recently, many reports were published supporting the clinical use of adoptively transferred natural killer (NK) cells as a therapeutic tool against cancer, including acute myeloid leukemia (AML). Our group demonstrated promising clinical response using adoptive immunotherapy with donor-derived alloreactive KIR-ligand-mismatched NK cells in AML patients. Moreover, the antileukemic effect was correlated with the dose of infused alloreactive NK cells ("functional NK cell dose"). Herein, we update the results of our previous study on a cohort of adult AML patients (median age at enrollment 64) in first morphological complete remission (CR), not eligible for allogeneic stem cell transplantation. After an extended median follow-up of 55.5 months, 8/16 evaluable patients (50%) are still off-therapy and alive disease-free. Overall survival (OS) and disease-free survival (DFS) are related with the dose of infused alloreactive NK cells (≥2 × 10/kg).
Topics: Aged; Female; Histocompatibility Antigens; Histocompatibility Testing; Humans; Immunotherapy, Adoptive; Killer Cells, Natural; Leukemia, Myeloid, Acute; Male; Middle Aged; Prognosis; Treatment Outcome
PubMed: 35173709
DOI: 10.3389/fimmu.2021.804988 -
Nature Reviews. Clinical Oncology Apr 2023Despite the notable success of chimeric antigen receptor (CAR) T cell therapies in the treatment of certain haematological malignancies, challenges remain in optimizing... (Review)
Review
Despite the notable success of chimeric antigen receptor (CAR) T cell therapies in the treatment of certain haematological malignancies, challenges remain in optimizing CAR designs and cell products, improving response rates, extending the durability of remissions, reducing toxicity and broadening the utility of this therapeutic modality to other cancer types. Data from multidimensional omics analyses, including genomics, epigenomics, transcriptomics, T cell receptor-repertoire profiling, proteomics, metabolomics and/or microbiomics, provide unique opportunities to dissect the complex and dynamic multifactorial phenotypes, processes and responses of CAR T cells as well as to discover novel tumour targets and pathways of resistance. In this Review, we summarize the multidimensional cellular and molecular profiling technologies that have been used to advance our mechanistic understanding of CAR T cell therapies. In addition, we discuss current applications and potential strategies leveraging multi-omics data to identify optimal target antigens and other molecular features that could be exploited to enhance the antitumour activity and minimize the toxicity of CAR T cell therapy. Indeed, fully utilizing multi-omics data will provide new insights into the biology of CAR T cell therapy, further accelerate the development of products with improved efficacy and safety profiles, and enable clinicians to better predict and monitor patient responses.
Topics: Humans; Immunotherapy, Adoptive; Neoplasms; Genomics; Proteomics; Hematologic Neoplasms
PubMed: 36721024
DOI: 10.1038/s41571-023-00729-2 -
Biochemical Pharmacology Aug 2020In the last decade, there has been great advancement in manipulating the immune system or the cells of the immune system to bring about effective therapies. While... (Review)
Review
In the last decade, there has been great advancement in manipulating the immune system or the cells of the immune system to bring about effective therapies. While harnessing the immune system against cancer is not a new concept, successful reprograming with T cells with chimeric antigen receptor (CAR) forming CAR-T cell therapy has revolutionized the treatment landscape for patients with refractory, high-grade B cell malignancies. The journey from proof-of-concept to FDA-approved commercial CAR-T products has taken almost 3 decades and untold amount of efforts, resources and manpower. With the success of CD19 CAR adoptive cellular immunotherapy leading the charge, CARs targeting various malignancies are in various stages of active development, racing towards regulatory approval, and raising hopes of further breakthroughs in cancer treatment options. In this review we will highlight recent clinical developments of the B cell maturation antigen (BCMA) CAR-T therapy for multiple myeloma (MM) to showcase how innovative CAR designs, coupled with careful selection of tumor-associated antigens, used in combination with other therapeutic agents, could help overcome some of the current limitations experienced in CAR-T immunotherapy. More patients could benefit from novel upfront cell therapy trials, that when combined with the current established induction regimens could have the potential to recondition and alter tumor environments, help restore somnolent anti-tumor immunity, and induce more effective and durable remissions.
Topics: Animals; Humans; Immunotherapy; Immunotherapy, Adoptive; Neoplasms; Receptors, Chimeric Antigen
PubMed: 32446888
DOI: 10.1016/j.bcp.2020.114051 -
Transfusion Clinique Et Biologique :... Jun 2003Recognition of the importance of immune cells present in a hematopoietic graft has resulted in a significant change in the perception of allogeneic hematopoietic... (Review)
Review
Recognition of the importance of immune cells present in a hematopoietic graft has resulted in a significant change in the perception of allogeneic hematopoietic transplantation. Such a transplant modality is now perceived has a very efficient form of adoptive allogeneic immunotherapy unfortunately associated with significant toxicity.
Topics: Graft vs Host Reaction; Humans; Immunotherapy, Adoptive; Stem Cell Transplantation; T-Lymphocytes; Transplantation, Homologous
PubMed: 12798852
DOI: 10.1016/s1246-7820(03)00038-7 -
Digestive Diseases and Sciences Feb 2021Pancreatic cancer is a tumor with a high degree of malignancy, morbidity, and mortality. Immunotherapy is another important treatment for pancreatic cancer in addition... (Review)
Review
Pancreatic cancer is a tumor with a high degree of malignancy, morbidity, and mortality. Immunotherapy is another important treatment for pancreatic cancer in addition to surgery and chemotherapy, but its application in pancreatic cancer is very limited, which is related to the unique biological behavior of pancreatic cancer and the tumor microenvironment. The immunosuppressive microenvironment of pancreatic cancer is highly heterogeneous and presents challenges for immunotherapy. The transformation of tumor immunosuppressive microenvironment contributes to the response to tumor immunotherapy, such that the tumor undergoes functional reprogramming to change from immunologically "cold" to immunologically "hot." In this review, we summarized the research and progress in immunotherapy for pancreatic cancer, including immune checkpoint inhibitors, vaccines, adoptive T cell therapy, oncolytic viruses, and immunomodulators, and suggest that individualized, combination, and precise therapy should be the main direction of future immunotherapy in pancreatic cancer.
Topics: Humans; Immune Checkpoint Inhibitors; Immunologic Factors; Immunotherapy; Immunotherapy, Adoptive; Pancreatic Neoplasms; Tumor Microenvironment
PubMed: 32140943
DOI: 10.1007/s10620-020-06183-9 -
Methods in Cell Biology 2024Tumor-draining lymph nodes (tumor-DLNs) provide a rich source of tumor-reactive lymphocytes which can be used in adoptive immunotherapy (AIT) and that circumvent the...
Tumor-draining lymph nodes (tumor-DLNs) provide a rich source of tumor-reactive lymphocytes which can be used in adoptive immunotherapy (AIT) and that circumvent the need to resect autologous tumor, without the challenges and shortcomings associated with using autologous tumor or anti-CD3 monoclonal antibody. Bryostatin/Ionomycin (Bryo/Io) provide a useful method of activating tumor-DLNs such that they can readily be expanded to sufficient numbers to be used in AIT, and growing the tumor-DLN lymphocytes in the gamma chain cytokines IL-7 plus IL-15 is superior to IL-2 in terms of T cell numbers and phenotype. AIT with these cells induces tumor regression and provides protection against metastases and future tumor challenge. Here, we provide a stepwise protocol to sensitize tumor-DLN cells in donor mice, activate tumor-DLN T cells ex vivo using Bryo/Io, expansion of these cells in gamma chain cytokines and adoptive transfer of the expanded cells back into tumor-bearing hosts. Methods relevant to these experiments, such as injecting tumor cells intravenously and monitoring for pulmonary metastases, tumor volume measurement and resection, and use of luciferase-expressing tumor cells to monitor for metastases following resection, are described in detail. The methods outlined herein can be easily adapted to suit similar experiments across multiple tumor cell lines and syngeneic mouse models.
Topics: Mice; Animals; Immunotherapy, Adoptive; Bryostatins; Cytokines; Ionomycin; Lymph Nodes; Lymphocyte Activation; Mice, Inbred C57BL
PubMed: 38548419
DOI: 10.1016/bs.mcb.2023.04.002 -
Current Oncology Reports Nov 2015Immunologic approaches to cancer are over a century old. Over the years, the strategy has been fine-tuned from inciting infections in subjects to inhibiting negative... (Review)
Review
Immunologic approaches to cancer are over a century old. Over the years, the strategy has been fine-tuned from inciting infections in subjects to inhibiting negative regulatory signals from the innate immune system. Sarcomas are among the first tumors to be considered for immune interventions. From Coley's toxin to cytokine-based therapies to adoptive cell therapy, there have been numerous immunotherapeutic investigations in this patient population. A promising strategy includes adoptive T cell therapy which has been studied in small cohorts of synovial sarcoma, a subtype that is known to widely express the cancer testis antigen, NY-ESO-1. Additionally, recent data in metastatic melanoma and renal cell carcinoma demonstrate the utility and tremendous efficacy of immune checkpoint blockade with increased rates of durable responses compared to standard therapies. Responses in traditionally "non-immunogenic" tumors, such as lung and bladder cancers, provide ample rationale for the study of immune checkpoint inhibitors in sarcoma. While immunotherapy has induced some responses in sarcomas, further research will help clarify optimal patient selection for future clinical trials and new combinatorial immunotherapeutic strategies.
Topics: Antigens, Neoplasm; Humans; Immunotherapy, Adoptive; Molecular Targeted Therapy; Neoplasm Recurrence, Local; Patient Selection; Practice Guidelines as Topic; Programmed Cell Death 1 Receptor; Sarcoma
PubMed: 26423769
DOI: 10.1007/s11912-015-0476-7 -
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