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Current Opinion in Immunology Feb 2022Adoptive T cell therapy (ACT) with tumor-reactive lymphocytes can overcome the immune desert of poorly immunogenic tumors and instruct tumor eradication. Several hurdles... (Review)
Review
Adoptive T cell therapy (ACT) with tumor-reactive lymphocytes can overcome the immune desert of poorly immunogenic tumors and instruct tumor eradication. Several hurdles limit the efficacy of this strategy against solid tumor including, but not limited to, sub optimal T cell engraftment, tumor infiltration, poor tumor antigenicity/immunogenicity, and immunosuppressive or resistance mechanisms. Recent advances indicate that concomitant treatments can be set in place to offset such barriers. In this review, we highlight the beneficial effects of combining ACT with conventional chemo and/or radiotherapy. While originally classified as immunosuppressive, these methodologies can also promote the engraftment of ACT products, immunogenic cell death, and the reprogramming of more favorable microenvironments. Data indicates that systemic and local chemo/radiotherapy regimens promote intratumoral cytokine and chemokine upregulation, tumor antigen presentation and cross presentation, infiltration and in situ T cells reactivation. Here we review the most recent contributions supporting these notions and discuss further developments.
Topics: Antigens, Neoplasm; Cell- and Tissue-Based Therapy; Humans; Immunotherapy, Adoptive; Neoplasms; T-Lymphocytes; Tumor Microenvironment
PubMed: 34743069
DOI: 10.1016/j.coi.2021.10.004 -
Transfusion Apr 2003
Review
Topics: Dendritic Cells; Humans; Immunotherapy, Adoptive; United States; United States Food and Drug Administration
PubMed: 12662272
DOI: 10.1046/j.1537-2995.2003.00351.x -
Molecular Cancer Therapeutics Mar 2024In solid tumors, three main complementary approaches of adoptive T-cell therapies were successively developed: tumor-infiltrating lymphocytes, chimeric antigen receptor... (Review)
Review
In solid tumors, three main complementary approaches of adoptive T-cell therapies were successively developed: tumor-infiltrating lymphocytes, chimeric antigen receptor engineered T cells, and high-affinity T-cell receptor engineered T cells. In this review, we summarized rational and main results of these three adoptive T-cell therapies in solid tumors field and gave an overview of encouraging data and their limits. Then, we listed the major remaining challenges (including tumor antigen loss, on-target/off-tumor effect, tumor access difficulties and general/local immunosubversion) and their lines of research. Finally, we gave insight into the ongoing trials in solid tumor.
Topics: Humans; Immunotherapy, Adoptive; Neoplasms; T-Lymphocytes; Receptors, Antigen, T-Cell; Cell- and Tissue-Based Therapy
PubMed: 37903371
DOI: 10.1158/1535-7163.MCT-23-0310 -
Pathobiology : Journal of... 1991Adoptive immunotherapy is a treatment modality designed to correct a defective and/or insufficient host defense response to a malignant tumor. Recently, we have...
Adoptive immunotherapy is a treatment modality designed to correct a defective and/or insufficient host defense response to a malignant tumor. Recently, we have developed a large scale technology for the generation of tumor cytotoxic macrophages (MACs) from circulating precursor monocytes. These ex vivo matured and interferon-gamma-activated MACs were used for adoptive transfer in a total of 30 tumor patients by intravenous (n = 12), intraperitoneal (n = 11) and intrahepatic (n = 7) infusion. A biological response to autologous cell transfer was evident from low-grade fever, elevation of C-reactive protein, induction of the coagulation cascade and a rise in interleukin-6 in sera as well as in ascitic fluids. A clinical response was only seen upon intraperitoneal treatment and consisted of palliation of malignant ascites in 3 of 7 patients and in reduction of ascitic tumor markers (CEA, CA125). Future perspectives of MAC therapy in combination with macrophage colony-stimulating factor, bacterial endotoxins and synthetic derivatives as well as monoclonal antibodies against tumor-associated antigens are discussed. Furthermore, the ex vivo manipulation of the MAC system may offer the possibility to use these multifunctional, pleiotropic effector cells not only in malignancy but also for the therapy of complicated opportunistic infections and secondary bone marrow hypoplasia.
Topics: Cytotoxicity, Immunologic; Humans; Immunotherapy, Adoptive; Infusions, Intravenous; Infusions, Parenteral; Liver; Macrophage Activation; Macrophages; Neoplasms
PubMed: 1883523
DOI: 10.1159/000163658 -
Immunotherapy 2015Strategies aimed at stimulating the immune system against cancer have signaled a new era for designing new effective therapies for patients. Recent breakthroughs in... (Review)
Review
Strategies aimed at stimulating the immune system against cancer have signaled a new era for designing new effective therapies for patients. Recent breakthroughs in adoptive cellular therapy and in using checkpoint inhibitors for some patients have renewed much enthusiasm in this field. However, it has become apparent that tumors can use a multitude of inhibitory networks to effectively reduce antitumor immunity. This review discusses our current knowledge of these immune suppressive mechanisms used by tumors and describes potential new strategies that may counteract this problem resulting in significantly increasing therapeutic outcomes of adoptive immunotherapy in a higher proportion of patients.
Topics: Animals; Humans; Immune Tolerance; Immunotherapy, Adoptive; Neoplasms
PubMed: 26065476
DOI: 10.2217/imt.15.16 -
Bulletin Du Cancer Dec 2018ROLE OF THE HOSPITAL PHARMACIST IN THE MANAGEMENT OF A CATEGORY OF ADVANCED THERAPY MEDICINAL PRODUCT: CHIMERIC ANTIGEN RECEPTOR T-CELLS: Chimeric Antigen Receptor...
ROLE OF THE HOSPITAL PHARMACIST IN THE MANAGEMENT OF A CATEGORY OF ADVANCED THERAPY MEDICINAL PRODUCT: CHIMERIC ANTIGEN RECEPTOR T-CELLS: Chimeric Antigen Receptor T-cells (CART) belongs to a new class of medicine, Advanced Therapy Medicinal Product, such as define by the European Regulation 1394/2007, and more exactly to the category of gene therapy medicinal product. Their status of medicine, as well as genetically modified organisms, imposes a particular circuit at hospital while maintaining a way over the Hospital Pharmacy. The manipulation of genetically modified cells is not usual in pharmacy. It requires, besides the acquisition of new skills, a not insignificant reorganization of the teams and the rooms of the pharmacy as well as an adapted training of the staff. A good communication is essential between the various actors of the circuit. The hospital pharmacist plays a key role in the implementation of a circuit adapted to this new type of medicine. This article aims to identify the roles of the hospital pharmacist and more generally of the pharmacy in the management of CART. We shall detail the specificities of this type of medicine in every stage of the circuit and the adaptations necessary to realize to guarantee the quality and the safety of the treatment by CART. Beyond the implementation of the circuit in the hospital, the pharmacist has an important role to be played in the follow-up of the patients after administration in view of the complexity of the side effects and a certain role in the training of the teams to this new medicine. 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: Continuity of Patient Care; Genetic Therapy; Humans; Immunotherapy, Adoptive; Pharmacies; Pharmacists; Pharmacy Service, Hospital; Professional Role; Receptors, Chimeric Antigen; Safety; T-Lymphocytes
PubMed: 30686359
DOI: 10.1016/S0007-4551(19)30051-7 -
World Journal of Gastroenterology Mar 2015To assess the efficacy of immunotherapy with expanded activated autologous lymphocytes (EAALs) in gastric cancer. (Observational Study)
Observational Study
AIM
To assess the efficacy of immunotherapy with expanded activated autologous lymphocytes (EAALs) in gastric cancer.
METHODS
An observational study was designed to retrospectively analyze the clinical data of 84 gastric cancer patients, of whom 42 were treated by EAAL immunotherapy plus conventional treatment and another 42 only received conventional treatment (control group). EAALs were obtained by proliferation of peripheral blood mononuclear cells from patients followed by phenotype determination. Clinical data including age, gender, clinical stage, chemotherapeutic regimens, hospitalization, surgical, radiotherapy, and survival data were collected along with EAAL therapy details and side effects. Patients were followed and the relationship between treatment and overall survival (OS) data obtained for the immunotherapy and control groups were compared retrospectively. The safety of EAAL immunotherapy was also evaluated.
RESULTS
After in vitro culture and proliferation, the percentages of CD3+, CD3+CD8+, CD8+CD27+, CD8+CD28+, and CD3+CD16+/CD56+ cells increased remarkably (P < 0.05), while the percentages of CD3+CD4+, CD4+CD25+, and CD3-CD16+/CD56+ (natural killer cells) were overtly decreased (P < 0.05); no significant change was observed in CD4+CD25+CD127- cells (P = 0.448). Interestingly, OS in the immunotherapy group was significantly higher than that in the control group, with 27.0 and 13.9 mo obtained for the two groups, respectively (P = 0.028, HR = 0.573, 95%CI: 0.347-0.945). These findings indicated a 42.7% decrease in the risk of death. In addition, we found that clinical stage and application of EAAL immunotherapy were independent prognostic factors for gastric cancer patients. Indeed, the OS in stage IIIc and IV patients that had received surgery was prolonged after EAAL immunotherapy (P < 0.05). Importantly, in vitro induction and proliferation of EAAL were easy and biologically safe.
CONCLUSION
Overall, EAAL adoptive immunotherapy might prolong the OS in gastric cancer patients.
Topics: Blood Transfusion, Autologous; Cell Proliferation; Cells, Cultured; Humans; Immunophenotyping; Immunotherapy, Adoptive; Kaplan-Meier Estimate; Lymphocyte Transfusion; Lymphocytes; Neoplasm Staging; Phenotype; Proportional Hazards Models; Retrospective Studies; Stomach Neoplasms; Time Factors; Treatment Outcome; Tumor Escape
PubMed: 25759549
DOI: 10.3748/wjg.v21.i9.2777 -
Immunological Reviews Jun 1997Bone marrow transplantation (BMT) is the present treatment for hematological malignancies. Two major drawbacks of allogeneic BMT are graft-versus-host disease (GVHD) and... (Review)
Review
Bone marrow transplantation (BMT) is the present treatment for hematological malignancies. Two major drawbacks of allogeneic BMT are graft-versus-host disease (GVHD) and leukemia relapse. The use of HLA-matched siblings as marrow donors results in the best transplant outcome. Nonetheless, the results of clinical BMT reveal that the selection of MHC-identical donors' bone marrow (BM) is no guarantee for avoiding GVHD or ensuring disease-free survival even when donor and recipient are closely related. It is believed that non-MHC-encoded so-called minor histocompatibility antigens (mHag) are involved in both graft-versus-host and graft-versus-leukemia activities. The recent new insights into the chemical nature of mHag not only reveal their physiological function but, more importantly, provide insights into their role in BMT. Together with the information on the human mHag genetics and tissue distribution gathered in the past, we may now apply this knowledge to the benefit of human BMT. Directly relevant is the utility of mHag molecular typing for diagnostics in BM donor selection. Most promising is the use of mHag-specific cytotoxic T cells for adoptive immunotherapy of leukemia.
Topics: Animals; Bone Marrow Transplantation; Graft vs Host Disease; Humans; Immunotherapy, Adoptive; Minor Histocompatibility Antigens
PubMed: 9255626
DOI: 10.1111/j.1600-065x.1997.tb00978.x -
Journal of Immunology (Baltimore, Md. :... Jul 2023Immunotherapy development for solid tumors remains challenging, partially due to a lack of reproducible, cost-effective in vitro three-dimensional (3D) models to mimic...
Immunotherapy development for solid tumors remains challenging, partially due to a lack of reproducible, cost-effective in vitro three-dimensional (3D) models to mimic the heterogeneous and complex tumor microenvironment. Here, we investigate the cellular anti-tumor reactivity of αβ T cells engineered to express a defined γδ TCR (TEG A3). For that purpose, we developed a 3D cytotoxicity assay targeting cell line-derived spheroids or patient-derived tumor organoids formed in serum-free media. Tumor cell lysis by TEG A3 was monitored using the Incucyte S3 live-cell imaging system with the apoptosis marker caspase 3/7 green and endpoint readouts of IFN-γ secretion in the supernatant. The 3D cytotoxicity assay model system was able to adequately demonstrate TEG A3 reactivity toward targets expressing an isoform of CD277 (CD277J). To obtain a more complex heterogeneous tumor microenvironment, patient-derived organoids were mixed with unmatched patient-derived fibroblasts or matched cancer-associated fibroblasts. In all assays, we demonstrated the tumor target specificity of TEG A3, lysing tumor cells within 48 h. Our study demonstrates the utility of complex 3D cytotoxicity assay model systems incorporating the tumor microenvironment in the functional evaluation of T cell-based adoptive immunotherapy, providing a useful platform for early-stage preclinical development of immunotherapies.
Topics: Humans; Neoplasms; T-Lymphocytes; Immunotherapy, Adoptive; Immunotherapy; Cell- and Tissue-Based Therapy; Tumor Microenvironment
PubMed: 37294309
DOI: 10.4049/jimmunol.2200573 -
Expert Opinion on Biological Therapy Jan 2023New methods in cancer immunotherapy, such as chimeric antigen receptor (CAR)-T cells, have shown promising results in destroying malignant cells. However, limitations... (Review)
Review
INTRODUCTION
New methods in cancer immunotherapy, such as chimeric antigen receptor (CAR)-T cells, have shown promising results in destroying malignant cells. However, limitations and side effects of CAR-T cell therapy, such as graft-versus-host disease (GVHD), neurotoxicity, and cytokine release syndrome, have motivated researchers to investigate safer alternative cells like natural killer (NK) cells.
AREA COVERED
NK cells can effectively recognize hematologic malignant cells and destroy them. Many clinical and preclinical studies investigate the efficacy of CAR-NK cells in treating lymphoma and other hematologic malignancies. The results of published clinical trials and preclinical studies have shown that CAR-NK cells could be an appropriate choice for treating lymphoma. In this review, we discuss the characteristics of CAR-NK cells, their role in treating B-cell and T-cell lymphoma, and the challenges faced by using them. We also highlight clinical trials using CAR-NK cells for treating lymphoma.
EXPERT OPINION
CAR-NK cells have shown promising results in cancer therapy, especially B-cell lymphoma, with a much lower risk for GVHD, cytokine release syndrome, and neurotoxicity than CAR-T cells. Further investigations are required to overcome the obstacles of CAR-NK cell therapy, both generally, and in cancers like T-cell lymphoma.
Topics: Humans; Cytokine Release Syndrome; Killer Cells, Natural; Lymphoma; Immunotherapy; Immunotherapy, Adoptive; Lymphoma, T-Cell; Graft vs Host Disease
PubMed: 36453808
DOI: 10.1080/14712598.2022.2154601