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Nature Cancer Nov 2023
Topics: Humans; Multiple Myeloma; T-Lymphocytes; Immunotherapy, Adoptive
PubMed: 37993694
DOI: 10.1038/s43018-023-00637-5 -
Bulletin Du Cancer Jan 2020
Topics: Algorithms; Antineoplastic Agents; Artificial Intelligence; Cancer Vaccines; Career Mobility; France; Hospitals, Public; Humans; Immunotherapy, Adoptive; Neoplasms
PubMed: 32000969
DOI: 10.1016/j.bulcan.2020.01.008 -
Immunology Letters Jan 2020The success of genetically engineered T-cells modified with a chimeric antigen receptor as an adoptive cell immunotherapy and the subsequent last regulatory approvals of... (Review)
Review
The success of genetically engineered T-cells modified with a chimeric antigen receptor as an adoptive cell immunotherapy and the subsequent last regulatory approvals of products based on this therapy are leading to a crescent number of both academic and pharmaceutical industry clinical trials testing new approaches of this "living drugs". The aim of this review is to outline the latest developments and regulatory considerations in this field, with a particular emphasis to differences and similarities between academic and industry approaches and the role they should play to coexist and move forward together. To do that, the main considerations for the manufacturing process are firstly discussed, from the chimeric antigen receptor design to final production steps, passing through ex vivo T-cell handling, gene delivery methods, patient´s final product infusion observations or possible associated side effects of this treatment.
Topics: Academies and Institutes; Biopharmaceutics; Costs and Cost Analysis; Gene Editing; Genetic Engineering; Genetic Therapy; Genetic Vectors; Humans; Immunotherapy, Adoptive; Industry; Manufacturing Industry; Neoplasms; Receptors, Antigen, T-Cell; T-Lymphocytes
PubMed: 31669547
DOI: 10.1016/j.imlet.2019.10.014 -
Trends in Molecular Medicine Aug 2023Localized immunomodulation technologies are rapidly emerging as a new modality with the potential to revolutionize transplantation of cells and organs. In the past... (Review)
Review
Localized immunomodulation technologies are rapidly emerging as a new modality with the potential to revolutionize transplantation of cells and organs. In the past decade, cell-based immunomodulation therapies saw clinical success in the treatment of cancer and autoimmune diseases. In this review, we describe recent advances in engineering solutions for the development of localized immunomodulation techniques focusing on cellular and organoid transplantation. We begin by describing cell transplantation and highlighting notable clinical successes, particularly in the areas of stem cell therapy, chimeric antigen receptor (CAR)-T cell therapy, and islet transplantation. Next, we detail recent preclinical studies centered on genome editing and biomaterials to enhance localized immunomodulation. We close by discussing future opportunities to improve clinical and commercial success using these approaches to facilitate long-term immunomodulation technologies.
Topics: Humans; Immunomodulation; Immunotherapy, Adoptive; Gene Editing; Organoids; Stem Cell Transplantation
PubMed: 37301656
DOI: 10.1016/j.molmed.2023.05.008 -
International Journal of Molecular... May 2023Natural killer cells (NK) are innate lymphocytes endowed with the ability to recognize and kill cancer cells. Consequently, adoptive transfer of autologous or allogeneic... (Review)
Review
Natural killer cells (NK) are innate lymphocytes endowed with the ability to recognize and kill cancer cells. Consequently, adoptive transfer of autologous or allogeneic NK cells represents a novel opportunity in cancer treatment that is currently under clinical investigation. However, cancer renders NK cells dysfunctional, thus restraining the efficacy of cell therapies. Importantly, extensive effort has been employed to investigate the mechanisms that restrain NK cell anti-tumor function, and the results have offered forthcoming solutions to improve the efficiency of NK cell-based therapies. The present review will introduce the origin and features of NK cells, summarize the mechanisms of action and causes of dysfunction of NK cells in cancer, and frame NK cells in the tumoral microenvironment and in the context of immunotherapies. Finally, we will discuss therapeutic potential and current limitations of NK cell adoptive transfer in tumors.
Topics: Humans; Neoplasms; Killer Cells, Natural; Immunotherapy, Adoptive; Immunotherapy; Adoptive Transfer; Tumor Microenvironment
PubMed: 37298470
DOI: 10.3390/ijms24119521 -
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 -
Seminars in Hematology Jan 2023Testing for measurable residual disease (MRD) provides important prognostic and predictive implications on survival and management of many hematologic diseases. Among... (Review)
Review
Testing for measurable residual disease (MRD) provides important prognostic and predictive implications on survival and management of many hematologic diseases. Among the many clinical uses of MRD is post-therapy response assessment and risk stratification. With the integration of precision medicine in routine clinical care and the development of novel and innovative therapies resulting in deeper responses, it is necessary to refine the role of MRD, standardize available methodologies and define its role as a surrogate endpoint for relapse and time-to-next treatment in clinical studies. Chimeric Antigen Receptor (CAR) T-cell therapy is an approved treatment for various hematologic malignancies. Even though it produces high rates of remission, the durability of response is still a consideration as almost 40% to 50% of patients eventually relapse. MRD testing as a prognostic and surrogate marker is being explored in patients after CAR T-cell therapy to predict early relapse. In this chapter, we review the various tools available for MRD detection and monitoring post-CAR T-cell therapy. We later discuss disease-specific MRD assessment and its application in recent studies in the post-CAR T setting.
Topics: Humans; Immunotherapy, Adoptive; Neoplasm Recurrence, Local; Prognosis; Neoplasm, Residual
PubMed: 37080709
DOI: 10.1053/j.seminhematol.2023.02.001 -
Current Hematologic Malignancy Reports Dec 2023The current review focuses on the preclinical development and clinical advances of natural killer (NK) cell therapeutics for hematologic malignancies and offers... (Review)
Review
PURPOSE OF REVIEW
The current review focuses on the preclinical development and clinical advances of natural killer (NK) cell therapeutics for hematologic malignancies and offers perspective on the unmet challenges that will direct future discovery in the field.
RECENT FINDINGS
Approaches to improve or re-direct NK cell anti-tumor functions against hematologic malignancies have included transgenic expression of chimeric antigen receptors (CARs), administration of NK cell engagers including BiKEs and TriKEs that enhance antibody-dependent cellular cytotoxicity (ADCC) by co-engaging NK cell CD16 and antigens on tumors, incorporation of a non-cleavable CD16 that results in enhanced ADCC, use of induced memory-like NK cells alone or in combination with CARs, and blockade of NK immune checkpoints to enhance NK cytotoxicity. Recently reported and ongoing clinical trials support the feasibility and safety of these approaches. NK cell-based therapeutic strategies hold great promise as cost-effective, off-the-shelf cell therapies for patients with relapsed and refractory hematologic diseases.
Topics: Humans; Immunotherapy, Adoptive; Killer Cells, Natural; Neoplasms; Receptors, Chimeric Antigen; Hematologic Neoplasms
PubMed: 37751103
DOI: 10.1007/s11899-023-00711-w -
European Journal of Cancer (Oxford,... Nov 2023Immunotherapy has ignited hope to cure paediatric solid tumours that resist traditional therapies. Among the most promising methods is adoptive cell therapy (ACT).... (Review)
Review
Immunotherapy has ignited hope to cure paediatric solid tumours that resist traditional therapies. Among the most promising methods is adoptive cell therapy (ACT). Particularly, ACT using T cells equipped with chimeric antigen receptors (CARs) has moved into the spotlight in clinical studies. However, the efficacy of ACT is challenged by ACT-intrinsic factors, like lack of activation or T cell exhaustion, as well as immune evasion strategies of paediatric solid tumours, such as their highly immunosuppressive microenvironment. Novel strategies, including ACT using innate-like lymphocytes, innovative cell engineering techniques, and ACT combination therapies, are being developed and will be crucial to overcome these challenges. Here, we discuss the main classes of ACT for the treatment of paediatric extracranial solid tumours, reflect on the available preclinical and clinical evidence supporting promising strategies, and address the challenges that ACT is still facing. Ultimately, we highlight state-of-the-art developments and opportunities for new therapeutic options, which hold great potential for improving outcomes in this challenging patient population.
Topics: Humans; Child; Immunotherapy, Adoptive; Neoplasms; T-Lymphocytes; Receptors, Chimeric Antigen; Immunotherapy; Tumor Microenvironment
PubMed: 37832507
DOI: 10.1016/j.ejca.2023.113347 -
International Journal of Molecular... Jun 2021Immunotherapy is now considered an innovative and strong strategy to beat metastatic, drug-resistant, or relapsing tumours. It is based on the manipulation of several... (Review)
Review
Immunotherapy is now considered an innovative and strong strategy to beat metastatic, drug-resistant, or relapsing tumours. It is based on the manipulation of several mechanisms involved in the complex interplay between cancer cells and immune system that culminates in a form of immune-tolerance of tumour cells, favouring their expansion. Current immunotherapies are devoted enforcing the immune response against cancer cells and are represented by approaches employing vaccines, monoclonal antibodies, interleukins, checkpoint inhibitors, and chimeric antigen receptor (CAR)-T cells. Despite the undoubted potency of these treatments in some malignancies, many issues are being investigated to amplify the potential of application and to avoid side effects. In this review, we discuss how sphingolipids are involved in interactions between cancer cells and the immune system and how knowledge in this topic could be employed to enhance the efficacy of different immunotherapy approaches. In particular, we explore the following aspects: how sphingolipids are pivotal components of plasma membranes and could modulate the functionality of surface receptors expressed also by immune cells and thus their functionality; how sphingolipids are related to the release of bioactive mediators, sphingosine 1-phosphate, and ceramide that could significantly affect lymphocyte egress and migration toward the tumour milieu, in addition regulating key pathways needed to activate immune cells; given the renowned capability of altering sphingolipid expression and metabolism shown by cancer cells, how it is possible to employ sphingolipids as antigen targets.
Topics: Animals; Antigens, Neoplasm; Cell Communication; Disease Management; Disease Susceptibility; Humans; Immune System; Immunomodulation; Immunotherapy; Immunotherapy, Adoptive; Lysophospholipids; Neoplasms; Signal Transduction; Sphingolipids; Sphingosine; Treatment Outcome
PubMed: 34204326
DOI: 10.3390/ijms22126492