scholarly journals Perspectives of tumor-infiltrating lymphocyte treatment in solid tumors

BMC Medicine ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Shuhang Wang ◽  
Jingwei Sun ◽  
Kun Chen ◽  
Peiwen Ma ◽  
Qi Lei ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Solid Tumors ◽  
Clinical Application ◽  
Cellular Therapy ◽  
Adoptive Cellular Therapy ◽  
Future Directions ◽  
Cellular Therapies ◽  
Tumor Infiltrating Lymphocyte ◽  
Tumor Homing

AbstractTumor-infiltrating lymphocyte (TIL) therapy is a type of adoptive cellular therapy by harvesting infiltrated lymphocytes from tumors, culturing and amplifying them in vitro and then infusing back to treat patients. Its diverse TCR clonality, superior tumor-homing ability, and low off-target toxicity endow TIL therapy unique advantages in treating solid tumors compared with other adoptive cellular therapies. Nevertheless, the successful application of TIL therapy currently is still limited to several types of tumors. Herein in this review, we summarize the fundamental work in the field of TIL therapy and the current landscape and advances of TIL clinical trials worldwide. Moreover, the limitations of the current TIL regimen have been discussed and the opportunities and challenges in the development of next-generation TIL are highlighted. Finally, the future directions of TIL therapy towards a broader clinical application have been proposed.

scholarly journals Augmented expansion of Treg cells from healthy and autoimmune subjects via adult progenitor cell co-culture

2020 ◽  
Author(s):  
JL Reading ◽  
VD Roobrouck ◽  
CM Hull ◽  
PD Becker ◽  
J Beyens ◽  
...  
Keyword(s):  
T Cell ◽  
Treg Cell ◽  
Regulatory T Cell ◽  
Cellular Therapy ◽  
Ex Vivo ◽  
Fold Increase ◽  
Adoptive Cellular Therapy ◽  
T Cell Therapy

AbstractRecent clinical experience has demonstrated that adoptive regulatory T cell therapy is a safe and feasible strategy to suppress immunopathology via induction of host tolerance to allo- and autoantigens. However, clinical trials continue to be compromised due to an inability to manufacture a sufficient Treg cell dose. Multipotent adult progenitor cells (MAPCⓇ) promote regulatory T cell differentiation in vitro, suggesting they may be repurposed to enhance ex vivo expansion of Tregs for adoptive cellular therapy. Here, we use a GMP compatible Treg expansion platform to demonstrate that MAPC cell-co-cultured Tregs (MulTreg) exhibit a log-fold increase in yield across two independent cohorts, reducing time to target dose by an average of 30%. Enhanced expansion is linked with a distinct Treg cell-intrinsic transcriptional program, characterized by diminished levels of core exhaustion (BATF, ID2, PRDM1, LAYN, DUSP1), and quiescence (TOB1, TSC22D3) related genes, coupled to elevated expression of cell-cycle and proliferation loci (MKI67, CDK1, AURKA, AURKB). In addition, MulTreg display a unique gut homing (CCR7lo β7hi) phenotype and importantly, are more readily expanded from patients with autoimmune disease compared to matched Treg lines, suggesting clinical utility in gut and/or Th1-driven pathology associated with autoimmunity or transplantation. Relative to expanded Tregs, MulTreg retain equivalent and robust purity, FoxP3 TSDR demethylation, nominal effector cytokine production and potent suppression of Th1-driven antigen specific and polyclonal responses in vitro and xeno graft vs host disease (xGvHD) in vivo. These data support the use of MAPC cell co-culture in adoptive Treg therapy platforms as a means to rescue expansion failure and reduce the time required to manufacture a stable, potently suppressive product.

IMMU-23. NEOANTIGEN-DIRECTED CELLULAR THERAPY IN A PRECLINICAL MOUSE MODEL OF MALIGNANT GLIOMA

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi96-vi97
Author(s):  
Max Schaettler ◽  
Gavin Dunn
Keyword(s):  
T Cells ◽  
Cell Therapy ◽  
Cd8 T Cells ◽  
Cellular Therapy ◽  
Immunological Tolerance ◽  
Dependent Manner ◽  
Adoptive Cellular Therapy ◽  
Specific Expression ◽  
Cervical Lymph Nodes

Abstract Adoptive cellular therapy in the form of CAR T cells or TCR engineered T cells has emerged as a novel approach in the treatment of both solid and hematologic malignancies. Neoantigens generated by tumor somatic mutations represent potentially attractive therapeutic targets in this context owing to their tumor-specific expression and circumvention of immunological tolerance. However, existing cell therapy systems generally target self-proteins or virally overexpressed antigens that fail to recapitulate the features of endogenous tumor neoantigens. Thus, there exists a need for a model in which tumor-specific neoantigens can be targeted via adoptive cellular therapy. Prior work from our lab identified the Imp3D81N mutation (mImp3) within GL261 as a neoantigen recognized by CD8 T cells in both intracranial tumors and draining cervical lymph nodes. To generate a system for targeting this neoantigen, we isolated and cloned mImp3-specific TCRs through a single-cell sort followed by a nested multiplexed PCR reaction. The specificity and functionality of these isolated TCRs was determined through introduction into a T cell hybridoma, identifying a top candidate based upon a high degree of cytokine production and specificity for the mutant epitope. A TCR transgenic mouse was then generated in which more than 90% of all T cells were CD8 T cells bearing this mImp3-specific TCR. T cells isolated from this mouse display specificity for the mImp3 peptide and display in vitro reactivity to GL261 and other cell lines in a mImp3-dependent manner. Therefore, this model represents the first TCR transgenic targeting a brain tumor neoantigen, opening the door for further investigation into cell therapy against this class of antigens.

scholarly journals Manufacture of Platelets from Human Adipose Tissue-Derived Mesenchymal Stromal/Stem Cells: Functional Comparison to Concentrate Platelets

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 1028-1028
Author(s):  
Keiichi Tozawa ◽  
Yukako Ono-Uruga ◽  
Masaki Yazawa ◽  
Taisuke Mori ◽  
Noriko Takizawa ◽  
...  
Keyword(s):  
Stem Cells ◽  
Clinical Application ◽  
Research Funding ◽  
Cellular Therapy ◽  
Recipient Mouse ◽  
Blood Samples ◽  
Equity Ownership ◽  
Induced Aggregation ◽  
Kinetics Of

Abstract We have established human adipose-derived mesenchymal stromal/stem cell line (ASCL) as an expandable cell source to generate megakaryocytes (MKs) releasing platelets for clinical transfusion. The use of ASCL has an advantage in manufacturing platelets, because both establishment of ASCL and its differentiation to MKs and platelets do not require gene transfer, and its endogenous thrombopoietin (TPO) is utilized for their differentiation. Here we report characterization of ASCL and ASCL-derived platelets for clinical application. ASCL retained their proliferation capacity for 6 months. There was no abnormality by karyotype analysis for ASCL, and no gene mutations registered in database for cancer and other diseases were noted by next-generation sequence analysis (n=3). ASCL satisfies the minimal criteria for defining mesenchymal stem cells by The International Society for Cellular Therapy: (1) adherence to plastic in vitro culture, (2) expression (>95% of cells) of CD73, CD90, and CD105 and no expression (<2% of cells) of CD45, CD34, CD14, CD19, and HLA-DR, and (3) capacity to differentiate into osteoblasts, adipocytes, and chondrocytes in vitro. ASCL was cultured in 10 liters of MK lineage induction media using a bioreactor. The frequency of CD41-expressing MK-sized cells increased during this culture with a peak at Day 8 (60-70%). We detected increased gene expression of TPO, p45NF-E2, beta-1 tubulin, VWF, GATA2, PF4, FOG1, and Fli1 during this differentiation. ASCL-derived platelets were obtained with a peak at Day 12 with 30-50 platelets released from a single MK. The expression of intracellular factors, VWF, PF4, and beta-1 tubulin in these platelets (CD42b-positive/anuclear platelet-sized cells) was also observed by immunostaining. We next compared functionality of ASCL-derived platelets and concentrate platelets (CP) from the Japanese Red Cross Society. Upon stimulation with thrombin (0.5 U/mL), surface exposure of PAC-1 in ASCL-derived platelets was higher than that in CP (p<0.05). Similar to PAC-1 surface exposure, the binding of labeled fibrinogen or P-selectin to ASCL-derived platelets was higher than that to CP, though the differences were not statistically significant. A sufficient number of platelets were obtained to perform platelet aggregation study under light transmission aggregometry. Agonist (ADP 20 μM and calcium 10 mM)-induced aggregation was observed in both ASCL-derived platelets and CP. To investigate the kinetics of ASCL-derived platelets and CP, these cells (1 x 107 cells) were infused into irradiated immunodeficient NSG mice (2.0 Gy, 7 days). Blood samples from recipient mouse were analyzed for the presence of human platelets 0 mins, 30 mins, 2 hrs, and 24 hrs after infusion. The kinetics of ASCL-derived platelets was similar to those of CP at the peak with 2 hrs (n=3). We tested thrombus formation under flow condition. Blood samples labeled with anti-CD41 antibody (clone, SZ22) were perfused on a collagen-coated chip. Incorporation of cells expressing human CD41 into the thrombi was observed in both samples from ASCL-derived platelet- and CP-infused mouse. Taken together, manufacturing platelets from ASCL in a large-scale culture and CP showed the similar in vivo kinetics and function, further supporting the clinical application of our approach. Disclosures Ono-Uruga: AdipoSeeds Inc.: Equity Ownership. Okamoto:Nippon Shinyaku Co., Ltd.: Research Funding; Eisai Co., Ltd.: Research Funding; Toyama Chemical Co., Ltd.: Research Funding; Astellas Pharma Inc.: Research Funding; Kyowa Hakko Kirin Co., Ltd.: Research Funding; Sumitomo Dainippon Pharma Co., Ltd.: Research Funding; Otsuka Pharmaceutical Co., Ltd.: Honoraria, Research Funding; Chugai Pharmaceutical Co., Ltd.: Research Funding; Teijin Pharma Limited: Research Funding; Shionogi & Co., Ltd.: Research Funding; Bristol-Myers Squibb K.K.: Honoraria, Research Funding; Alexion Pharmaceuticals, Inc.: Research Funding; Asahi Kasei Pharma Corp.: Research Funding; Pfizer Inc.: Honoraria, Research Funding; JCR Pharmaceuticals Co., Ltd.: Research Funding. Ikeda:AdipoSeeds Inc.: Equity Ownership. Matsubara:AdipoSeeds Inc.: Equity Ownership; Kyowa Hakko Kirin Co., Ltd.: Research Funding; Tosoh Corporation: Research Funding; Nissui Pharmaceutical Co., Ltd.: Research Funding; Fujimori Kogyo Co., Ltd.: Research Funding.

A phase 1, first in human study of adenovirally transduced autologous macrophages engineered to contain an anti-HER2 chimeric antigen receptor (CAR) in subjects with HER2 overexpressing solid tumors.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. TPS2660-TPS2660
Author(s):  
Joshua Bauml ◽  
Natalie Sophia Grover ◽  
Amy Ronczka ◽  
Daniel Cushing ◽  
Michael Klichinsky ◽  
...  
Keyword(s):  
Solid Tumors ◽  
Cellular Therapy ◽  
Phase 1 ◽  
Locally Advanced ◽  
Human Study ◽  
Growth Factor Receptor ◽  
Immune Memory ◽  
Blood Monocytes ◽  
Adoptive Cellular Therapy ◽  
Cell Therapies

TPS2660 Background: Adoptive T cell therapies have led to remarkable advances among patients with hematologic malignancies, but not in those with solid tumors. Macrophages are actively recruited into, and abundantly present in the solid tumor microenvironment (sTME). Tumor- associated macrophages typically evince immunosuppressive behavior, but when engineered to be proinflammatory, may be an ideal vector to administer adoptive cellular therapy in solid tumors. Furthermore, insertion of a CAR confers on the macrophages the ability to selectively recognize and phagocytose antigen overexpressing cancer cells. Additionally, CAR macrophages reprogram the sTME and present neoantigens to T cells, leading to epitope spreading and immune memory. Human Epidermal Growth Factor Receptor 2 (HER2) is overexpressed in many cancers, including but not limited to breast and gastroesophageal cancers (Table). CT-0508 is a cell product comprised of autologous monocyte-derived pro-inflammatory macrophages expressing an anti-HER2 CAR. Pre-clinical studies have shown that CT-0508 induced targeted cancer cell phagocytosis while sparing normal cells, decreased tumor burden and prolonged survival in relevant models. CT-0508 cells were safe and effective in a semi-immunocompetent mouse model of human HER2 overexpressing ovarian cancer. Methods: This is a FIH phase 1 study to evaluate safety, tolerability, cell manufacturing feasibility, trafficking, and preliminary evidence of efficacy of investigational product CT-0508 in approximately 18 subjects with locally advanced (unresectable) or metastatic solid tumors overexpressing HER2 who have failed available therapies including anti-HER2 therapies when indicated. Filgrastim will be used to mobilize autologous hematopoietic progenitor cells for monocyte collection by apheresis. The CT-0508 CAR macrophage product will be manufactured, prepared and cryopreserved from mobilized peripheral blood monocytes. The study is enrolling Group 1 subjects, who will receive CT-0508 infusion split over D1, 3 and 5. Subjects will be continually assessed for acute and cumulative toxicity. Dose limiting toxicities will be observed and addressed by a Safety Review Committee. Group 2 subjects will follow, and will receive the full CT-0508 infusion on D1. Pre and post treatment biopsies and blood samples will be collected to investigate correlates of trafficking, persistence, TME modulation, immune response and safety. Clinical trial information: NCT04660929. [Table: see text]

Human CIK Maintain Their In Vitro and In Vivo Anti-Tumor Ability after Cryopreservation.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1062-1062
Author(s):  
Jeanette Baker ◽  
Kevin Sheehan ◽  
Gina Monterola ◽  
Nancy Staines ◽  
Robert S. Negrin
Keyword(s):  
T Cells ◽  
Cytotoxic Activity ◽  
Cellular Therapy ◽  
Cell Activity ◽  
B Cell Lymphoma ◽  
Dependent Manner ◽  
Adoptive Cellular Therapy ◽  
Cik Cells

Abstract Adoptive cellular therapy holds promise for improving the outcome of hematopoietic cell transplantation (HCT). At present, donor lymphocyte infusion post-HCT is efficacious for only a limited number of diseases, yet can induce significant graft versus host disease (GVHD). To improve the outcome of this approach, it would be beneficial to identify populations of T cells that retain graft versus tumor (GVT) effects with reduced propensity for GVHD. We have previously described studies of murine expanded Cytokine Induced Killer (CIK) cells which are ex vivo activated and expanded T cells that express both T and NK markers. CIK cells mediate cytotoxicity both in vivo and in vitro in a non- MHC restricted NKG2D dependent manner. Human CIK cells were expanded from PBMC from 9 healthy donors, cultured with IFNg, CD3 and IL-2 and maintained in AastromRepliCell® biochambers for 21–28 days. We aimed to determine whether cryopreservation of the CIK affects viability, cytotoxicity and phenotype. Cells were cryopreserved immediately after harvest at 10x106/ml and stored in liquid nitrogen vapor phase. CIK viability was not compromised with cryopreservation and cells thawed at 1, 2, 4, 8, 10 and 28 weeks after freezing were 96% viable (range 95%–99%). Immediately upon thawing, CIK cells showed diminished cytotoxicity against the B cell lymphoma cell lines DB and SUDHL4 with 6–10% killing at the 40:1 E:T ratio. However, thawed CIK cells regained their pre-freeze cytotoxic activity against these targets within 5 hours of being placed in reactivation medium containing IL-2 at 300 IU/ml. Reactivation of the CIK cells was extended up to 48 hours but showed no further increase in cytotoxicity beyond that attained at 5 hours; nor did increasing the IL-2 concentration to 1500 IU/ml in the reactivation medium improve CIK cell activity over the same time course. Cell viability declined during reactivation, decreasing from an average 96% upon thawing to 60% over 48 hours. Thawed CIK cells placed in reactivation medium maintained their cytotoxic activity up to 14 days in vitro. The cytotoxicity of reactivated CIK cells was assessed in vivo using SCID mice inoculated IP with 1x106 human ovarian cancer UCI-101 cells expressing the firefly luciferase gene. The mice were treated weekly with 2x107 cryopreserved and thawed human CIK cells that were re-cultured for 5 hours before injection. Following each administration of CIK cells, there was a reduction of tumor signal. Weekly treatments resulted in a better survival outcome for the mice receiving CIK cells as compared to PBS control mice. This study demonstrates that human CIK cells may be reactivated after cryopreservation and regain their cytotoxic potential. These finding have important implications for the application of these cells as adoptive cellular therapy.

scholarly journals Using Expanded Natural Killer Cells as Therapy for Invasive Aspergillosis

2020 ◽  
Vol 6 (4) ◽  
pp. 231
Author(s):  
Win Mar Soe ◽  
Joan Hui Juan Lim ◽  
David L. Williams ◽  
Jessamine Geraldine Goh ◽  
Zhaohong Tan ◽  
...  
Keyword(s):  
Invasive Aspergillosis ◽  
Nk Cells ◽  
Fungicidal Activity ◽  
Cellular Therapy ◽  
Nk Cell ◽  
Adjunctive Treatment ◽  
Fungal Treatment ◽  
Adoptive Cellular Therapy

Invasive aspergillosis (IA) is a major opportunistic fungal infection in patients with haematological malignancies. Morbidity and mortality rates are high despite anti-fungal treatment, as the compromised status of immune system prevents the host from responding optimally to conventional therapy. This raises the consideration for immunotherapy as an adjunctive treatment. In this study, we evaluated the utility of expanded human NK cells as treatment against Aspergillus fumigatus infection in vitro and in vivo. The NK cells were expanded and activated by K562 cells genetically modified to express 4-1BB ligand and membrane-bound interleukin-15 (K562-41BBL-mbIL-15) as feeders. The efficacy of these cells was investigated in A. fumigatus killing assays in vitro and as adoptive cellular therapy in vivo. The expanded NK cells possessed potent killing activity at low effector-to-target ratio of 2:1. Fungicidal activity was morphotypal-dependent and most efficacious against A. fumigatus conidia. Fungicidal activity was mediated by dectin-1 receptors on the expanded NK cells leading to augmented release of perforin, resulting in enhanced direct cytolysis. In an immunocompromised mice pulmonary aspergillosis model, we showed that NK cell treatment significantly reduced fungal burden, hence demonstrating the translational potential of expanded NK cells as adjunctive therapy against IA in immunocompromised patients.

In Vitro Expansion of CMV-Specific T Cells from CMV Seronegative Donors.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3927-3927
Author(s):  
Stephanie Verfuerth ◽  
Arnold R. Pizzey ◽  
Shoon-Ling C. Chow ◽  
Noha Chowdhry ◽  
Stephen Mackinnon
Keyword(s):  
Cell Proliferation ◽  
T Cells ◽  
T Cell ◽  
Cellular Therapy ◽  
T Cell Proliferation ◽  
Adoptive Cellular Therapy ◽  
Size Classes ◽  
Pulsed Dc ◽  
Ifn Γ

Abstract CMV infection is still a negative prognostic factor in hematopoietic stem cell transplantation, largely due to adverse effects of antiviral chemotherapy. Advances have been made in the development of adoptive cellular therapy for CMV with cell products derived from CMV seropositive donors. However no such cell products from CMV negative donors are currently available, although CMV negative recipients of CMV positive grafts bear the greatest risk of CMV induced morbidity and mortality. Mature DC are capable of inducing in vivo primary T cell responses. We used an in vitro culture system employing MoDC generated with GM-CSF and IL-4, pulsed with CMV lysate and matured with CD40L to induce primary immune responses to CMV. CMV-specific T cell proliferation measured by 3H-Thymidine uptake could be induced in some 6 to 9-day cultures, however, the success rate was very low, and T cells could usually not be kept alive after becoming activated. The addition of IL-15 to cultures after 7 days resulted in some improvement, although some non-CMV specific T cell proliferation in response to control lysate or in the absence of antigen also occurred in some cultures. IL-12 added to cultures from day 0 resulted in a short-term increase in T cell proliferation that was followed by increased cell death and was also not entirely CMV-specific. The real benefit of IL-15, alone or in combination with IL-12, was seen in 2-week cultures: In 6/7 cultures from different CMV seronegative donors counts of viable T cells (by trypan blue exclusion) increased up to 10-fold. Two cultures that were additionally set up with control lysate-pulsed DC to detect proliferation in response to non-CMV components of the antigen, confirmed CMV-specificity. CMV-specificity was also shown by T cell receptor (TCR) complement determining region (CDR) 3 spectratyping. TCR-BV(variable region β)-size class expression patterns across 23 BV families were very similar in pre-culture unstimulated T cells and in T cells stimulated with control lysate-pulsed DC for 2 weeks, showing the typical near-normal distribution of PCR product amongst the different size classes indicative of un-stimulated T cells. T cells co-cultured with CMV lysate-pulsed DC for 2 weeks produced very skewed spectratypes, indicative of oligoclonal T cell expansion in response to the antigen. The effect of IL-15 on T cell spectratypes from CMV antigen-driven cultures was tested using cells from another donor. With or without IL-15, post-culture spectratypes showed oligoclonal T cell expansions in the same BV families and size classes. However, despite their similar shapes, spectratypes from IL-5 containing cultures were skewed to a greater extent, possibly indicating a greater effect of IL-15 on already activated T cells. No CD8+ T cells specific for single immunodominant epitopes could be detected by staining with up to 5 different HLA-CMVpeptide-tetramers in culture output from 4/4 donors. In 1 of 2 cultures analyzed by cytokine secretion assay, a significant sub-population of T cells (1%), in CD4 positive and negative fractions, secreted IFN-γ in response to re-stimulation with CMV antigen. No IFN-γ secreting CMV-specific pre-cursor T cells were detected in fresh PBMC, as expected. Whilst further work is required to make generation of CMV specific T cells from CMV seronegative donors more reproducible and to ensure antigen-specificity, these preliminary data are encouraging for the future generation of CMV-specific T cells from CMV seronegative donors for adoptive cellular therapy.

scholarly journals IL-21–mediated Foxp3 suppression leads to enhanced generation of antigen-specific CD8+ cytotoxic T lymphocytes

Blood ◽  
2008 ◽  
Vol 111 (1) ◽  
pp. 229-235 ◽  
Author(s):  
Yongqing Li ◽  
Cassian Yee
Keyword(s):  
T Cells ◽  
T Lymphocytes ◽  
Cytotoxic T Lymphocytes ◽  
Cellular Therapy ◽  
Ex Vivo ◽  
Human Model ◽  
Adoptive Cellular Therapy ◽  
Specific Ctls ◽  
Regulatory Constraints

Efforts to reproducibly isolate tumor antigen–specific T cells from patients would be facilitated by removing immunoregulatory barriers. Using a human model for eliciting T-cell responses to tumor-associated antigens, we develop a novel strategy that eliminates nearly all Foxp3-expressing cells through the combination of CD25 depletion and IL-21 treatment resulting in a more than 150-fold decrease in Foxp3+ cells to virtually undetectable levels and a more than 200-fold increase in antigen-specific cytotoxic T lymphocytes (CTLs). The extent of Foxp3 elimination and degree of expansion of antigen-specific CTLs shown in this study have not previously been achievable and are unique to IL-21. We demonstrate for the first time a possible mechanism for IL-21–mediated expansion of antigen-specific CTLs that involves suppression of Foxp3-expressing cells and reversal of inhibition to tumor-associated antigen–specific CTL generation in vitro. Taken together, the combination of CD25 depletion and IL-21 exposure, by releasing regulatory constraints, leads to markedly enhanced CTL induction and represents a robust strategy for the ex vivo generation of antigen-specific T cells for adoptive cellular therapy.

scholarly journals Clinical Trials with Combination of Cytokine-Induced Killer Cells and Dendritic Cells for Cancer Therapy

2019 ◽  
Vol 20 (17) ◽  
pp. 4307 ◽  
Author(s):  
Francesca Garofano ◽  
Maria A. Gonzalez-Carmona ◽  
Dirk Skowasch ◽  
Roland Schmidt-Wolf ◽  
Alina Abramian ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Dendritic Cells ◽  
Cellular Therapy ◽  
Residual Tumor ◽  
Allogeneic Transplantation ◽  
Cellular Immunotherapy ◽  
Adoptive Cellular Therapy ◽  
Surgical Ablation ◽  
Killer Cells ◽  
Cik Cells

Adoptive cellular immunotherapy (ACI) is a promising treatment for a number of cancers. Cytokine-induced killer cells (CIKs) are considered to be major cytotoxic immunologic effector cells. Usually cancer cells are able to suppress antitumor responses by secreting immunosuppressive factors. CIKs have significant antitumor activity and are capable of eradicating tumors with few side effects. They are a very encouraging cell population used against hematological and solid tumors, with an inexpensive expansion protocol which could yield to superior clinical outcome in clinical trials employing adoptive cellular therapy combination. In the last decade, clinical protocols have been modified by enriching lymphocytes with CIK cells. They are a subpopulation of lymphocytes characterized by the expression of CD3+ and CD56+ wich are surface markers common to T lymphocytes and natural killer NK cells. CIK cells are mainly used in two diseases: in hematological patients who suffer relapse after allogeneic transplantation and in patients with hepatic carcinoma after surgical ablation to eliminate residual tumor cells. Dendritic cells DCs could play a pivotal role in enhancing the antitumor efficacy of CIKs.

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