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[Rinsho Ketsueki] the Japanese Journal... 2016Adoptive immunotherapy using chimeric antigen receptor (CAR)-modified T cells has provided a major breakthrough in the treatment of hematological malignancies. In Japan,...
Adoptive immunotherapy using chimeric antigen receptor (CAR)-modified T cells has provided a major breakthrough in the treatment of hematological malignancies. In Japan, it is expected that CD19 CAR-T cell therapy will be introduced earlier in clinical B cell malignancy settings and/or that a novel CAR-T cell therapy will be developed for non-B cell malignancies. The "Act on the Safety of Regenerative Medicine" and the "Revised Pharmaceutical Affairs Act" were promulgated in 2014. Both Acts were very important to the introduction and development of CAR-T therapy in Japan. "Specified cell products" produced according to the former Act can be used in clinical research projects, while "regenerated medical products" produced according to the latter Act can be used in clinical trials, having been launched on the market. In this chapter, we will summarize the regulations pertaining to adoptive immunotherapy on the basis of these two essential Acts.
Topics: Cell Culture Techniques; Cell Separation; Humans; Immunotherapy, Adoptive; Neoplasms; Regeneration; Risk Management
PubMed: 27941288
DOI: 10.11406/rinketsu.57.2373 -
Critical Reviews in Immunology 2000Tumor-specific CD4+ effector T cells often play a decisive role in immunologic tumor rejection, in some cases without evident co-participation of CD8+ T cells. During... (Review)
Review
Tumor-specific CD4+ effector T cells often play a decisive role in immunologic tumor rejection, in some cases without evident co-participation of CD8+ T cells. During such CD4+ T-cell-mediated rejection there is often no detectable direct contact between T cells and tumor cells. Optimally prepared, adoptively transferred CD4+ T cells can reject established tumors with great efficiency even when targeted tumor cells express no MHC Class II molecules, implying that recognition of tumor antigen (Ag) occurs via MHC Class II-expressing host antigen-presenting cells (APC) within the tumor. Because consequent rejection also excludes Ag-specific contact between CD4+ T cells and MHC Class IIneg tumor cells, the most critical CD4+ T-cell-mediated event is likely cytokine release, resulting in an accumulation and activation of accessory cells such as tumoricidal macrophages and lymphokine-activated killer cells. Although such an indirect rejection mechanism may appear antithetical to popular strategies centered on CD8+ cytotoxic T cell (CTL), current evidence suggest that even CD8+ T-cell-mediated recognition/rejection often bypasses direct tumor cell contact and is largely cytokine mediated. While CTL are likely to participate prominently in many models of tumor rejection, indirect mechanisms of recognition/rejection have the theoretical advantage of remaining operative even when individual tumor cells evade direct contact by down-regulating MHC and/or Ag expression.
Topics: Animals; CD4-Positive T-Lymphocytes; Humans; Immunotherapy, Adoptive; Neoplasms
PubMed: 10770269
DOI: No ID Found -
Immunological Reviews Nov 2023Adoptive T-cell transfer (ACT) therapies, including of tumor infiltrating lymphocytes (TILs) and T cells gene-modified to express either a T cell receptor (TCR) or a... (Review)
Review
Adoptive T-cell transfer (ACT) therapies, including of tumor infiltrating lymphocytes (TILs) and T cells gene-modified to express either a T cell receptor (TCR) or a chimeric antigen receptor (CAR), have demonstrated clinical efficacy for a proportion of patients and cancer-types. The field of ACT has been driven forward by the clinical success of CD19-CAR therapy against various advanced B-cell malignancies, including curative responses for some leukemia patients. However, relapse remains problematic, in particular for lymphoma. Moreover, for a variety of reasons, relative limited efficacy has been demonstrated for ACT of non-hematological solid tumors. Indeed, in addition to pre-infusion challenges including lymphocyte collection and manufacturing, ACT failure can be attributed to several biological processes post-transfer including, (i) inefficient tumor trafficking, infiltration, expansion and retention, (ii) chronic antigen exposure coupled with insufficient costimulation resulting in T-cell exhaustion, (iii) a range of barriers in the tumor microenvironment (TME) mediated by both tumor cells and suppressive immune infiltrate, (iv) tumor antigen heterogeneity and loss, or down-regulation of antigen presentation machinery, (v) gain of tumor intrinsic mechanisms of resistance such as to apoptosis, and (vi) various forms of toxicity and other adverse events in patients. Affinity-optimized TCRs can improve T-cell function and innovative CAR designs as well as gene-modification strategies can be used to coengineer specificity, safety, and function into T cells. Coengineering strategies can be designed not only to directly support the transferred T cells, but also to block suppressive barriers in the TME and harness endogenous innate and adaptive immunity. Here, we review a selection of the remarkable T-cell coengineering strategies, including of tools, receptors, and gene-cargo, that have been developed in recent years to augment tumor control by ACT, more and more of which are advancing to the clinic.
Topics: Humans; T-Lymphocytes; Immunotherapy, Adoptive; Immunotherapy; Receptors, Antigen, T-Cell; Receptors, Chimeric Antigen; Neoplasms; Antigens, Neoplasm; Tumor Microenvironment
PubMed: 37548063
DOI: 10.1111/imr.13252 -
Bulletin Du Cancer Dec 2018HOW CAN FRENCH HEALTHCARE PROVIDERS ADAPT THEIR ORGANIZATION TO REQUIREMENTS FOR MANUFACTURING AND DELIVERY OF THESE INNOVATIVE CELL-BASED MEDICINAL PRODUCTS?: More than... (Review)
Review
HOW CAN FRENCH HEALTHCARE PROVIDERS ADAPT THEIR ORGANIZATION TO REQUIREMENTS FOR MANUFACTURING AND DELIVERY OF THESE INNOVATIVE CELL-BASED MEDICINAL PRODUCTS?: More than five years after the first US publications reporting a significant rate of clinical responses in patients with high-risk or advanced CD19+ lymphoid malignancies, access to treatment with CAR-T Cells at European hospitals in general and at French hospitals in particular remains limited. One - and not the least - hurdle lay in the need to set up a complex and unprecedented organization that complies with European regulations on Advanced Therapy Medicinal Products as well as with national (French) regulations. We here review the organizational framework for two situations: delivery and administration of industry-manufactured CAR-T Cells as well as engineering and distribution of CAR-T Cells produced as investigational drugs to be evaluated in the context of clinical research protocols. Cet article fait partie du numéro supplément Les cellules CAR-T : une révolution thérapeutique ? réalisé avec le soutien institutionnel des partenaires Gilead : Kite et Celgene.
Topics: Drugs, Investigational; European Union; France; Health Facility Administration; Humans; Immunotherapy, Adoptive; Legislation, Drug; Receptors, Chimeric Antigen; T-Lymphocytes
PubMed: 30686358
DOI: 10.1016/S0007-4551(19)30050-5 -
Anticancer Research Feb 2011This review focuses on the relationship between pre-treatment immune parameter values and outcome of immunotherapy of cancer patients. The evidence presented in this... (Review)
Review
This review focuses on the relationship between pre-treatment immune parameter values and outcome of immunotherapy of cancer patients. The evidence presented in this review suggests that there is a relationship between pre-treatment immune parameter values and survival of cancer patients treated with immunotherapy. Tumour-infiltrating immune cells may have a predictive value for immunotherapy, but predictive power might be obtained from peripheral blood leukocytes. Use of peripheral blood may be preferable due to the convenience of collection and analysis compared to using tumour-infiltrating cells. In vivo numbers of cells of the immune system correlate better with clinical outcome than their functional activity ex vivo. This suggests that immunological antitumour mechanisms in vivo are not always related to generally accepted functional parameters of lymphocytes, such as cytotoxicity or cytokine production, ex vivo. The proliferative status of CD8(+) T lymphocytes seems promising for prediction of response in cancer immunotherapy.
Topics: Humans; Immunotherapy; Immunotherapy, Adoptive; Neoplasms
PubMed: 21378350
DOI: No ID Found -
Current Problems in Cancer Feb 2022Approaches to immunologic therapies in myelodysplastic syndromes (MDS) have generally fallen into 2 categories: therapies that target immune effector cells and enhance... (Review)
Review
Approaches to immunologic therapies in myelodysplastic syndromes (MDS) have generally fallen into 2 categories: therapies that target immune effector cells and enhance or direct an antileukemic effect, and therapies which target immunological markers on MDS progenitors themselves. Examples of the former include immune checkpoint inhibitors, immunomodulatory therapies, and vaccines, among others, while examples of the latter include antibody-drug conjugate therapies and naked antibodies; while bispecific antibodies and modified T-cells (such as CAR-T therapies) bridge both therapeutic modalities. In this review, we will discuss the rationale for the above therapies, clinical results to date, and potential future directions for investigation.
Topics: Humans; Immunotherapy; Immunotherapy, Adoptive; Medical Oncology; Myelodysplastic Syndromes; Neoplasms
PubMed: 34980485
DOI: 10.1016/j.currproblcancer.2021.100824 -
Current Research in Translational... May 2018The development of genomic editing technologies expands the landscape of T cell engineering for adoptive cell therapy. Among the multiple tools that can be used,... (Review)
Review
The development of genomic editing technologies expands the landscape of T cell engineering for adoptive cell therapy. Among the multiple tools that can be used, CRISPR/Cas9 has been shown to be relatively easy to use, simple to design and cost effective with highly efficient multiplex genome engineering capabilities. Allogeneic universal chimeric antigen receptor (CAR) T cells can be produced by disrupting T cell receptor (TCR) and beta-2-microglobulin (B2M) in CAR T cells or by directly knocking in a CAR at the disrupted TRAC locus. The anti-tumor function can be further boosted by simultaneous ablation of PD-1 and CTLA-4. The anti-tumor activities and safety of TCR-transferred T cells can be improved by knocking out endogenous TCR, which avoids the use of affinity-enhanced TCRs that may lose specificity and cause severe adverse effects. Therefore, CRISPR/Cas9 technology holds enormous promise to advance the field of adoptive cell therapy.
Topics: Animals; CRISPR-Cas Systems; Gene Editing; Humans; Immunotherapy, Adoptive; Neoplasms; Receptors, Chimeric Antigen; T-Lymphocytes
PubMed: 29691200
DOI: 10.1016/j.retram.2018.04.003 -
Annals of Oncology : Official Journal... Jan 2022
Topics: Academic Medical Centers; Humans; Immunotherapy, Adoptive; Neoplasms
PubMed: 34655734
DOI: 10.1016/j.annonc.2021.09.020 -
American Journal of Hematology May 2019CAR T cells have revolutionized the treatment of relapsed and refractory CD19-positive leukemia and lymphoma. Unfortunately, the majority of patients treated will not... (Review)
Review
CAR T cells have revolutionized the treatment of relapsed and refractory CD19-positive leukemia and lymphoma. Unfortunately, the majority of patients treated will not achieve durable remissions. Reasons for these suboptimal clinical outcomes can be tied back to intrinsic CAR T cell design and manufacturing processes, factors that are highly amenable to modification and improvement. As CAR T cell therapy is being deployed in spaces outside of CD19-positive disease, these limitations, complications, and setbacks need to be overcome, allowing for the full potential of this novel therapy to be realized. Preclinical work has begun tackling these major roadblocks, paving the way for potentially off-the-shelf products that are safer and more potent. In time, a number of these advances will be translated to the clinic and usher in an era of CARs of the future.
Topics: Forecasting; Humans; Immunotherapy, Adoptive; Receptors, Chimeric Antigen; Treatment Outcome
PubMed: 30680777
DOI: 10.1002/ajh.25416 -
Expert Opinion on Biological Therapy Feb 2005As part of the innate immune system, natural killer (NK) cells form the first line of defence against pathogens or transformed/cancerous host cells. Recent experimental... (Review)
Review
As part of the innate immune system, natural killer (NK) cells form the first line of defence against pathogens or transformed/cancerous host cells. Recent experimental and clinical data show the possibility of exploiting NK activity as a cell-based immunotherapy to treat cancer. This review discusses the recent knowledge on NK cell biology that has impacted on its development as a treatment for cancer.
Topics: Animals; Humans; Immunotherapy, Adoptive; Killer Cells, Natural; Neoplasms
PubMed: 15757378
DOI: 10.1517/14712598.5.2.163