scholarly journals Structural design of tetravalent T-cell engaging bispecific antibodies: improve developability by engineering disulfide bonds

2021 ◽  
Vol 15 (1) ◽  
Author(s):  
Lin Yu ◽  
Nan Huang ◽  
Liangpeng Ge ◽  
Heng Sun ◽  
Yuna Fu ◽  
...  
Keyword(s):  
T Cell ◽  
Disulfide Bonds ◽  
Tumor Antigens ◽  
Cytotoxic T Cells ◽  
Inhibitory Effect ◽  
Biological Properties ◽  
Binding Domain ◽  
Target Cells ◽  
Single Chain ◽  
Asymmetrical Design

AbstractSince the advances in protein engineering and manufacture, over the last 30 years, antibody-based immunotherapeutic has become a powerful strategy to treat diseases. The T-cell engaging bispecific antibody (BsAb) by combining the Fab binding domain of tumor antigens and Fab or single-chain variable fragments (scFvs) binding domain of CD3 molecules, could redirect cytotoxic T cells to kill tumor cells. The IgG-scFv format of BsAb is a dual bivalent and asymmetrical design, which adds the benefit of potent cytotoxicity and less complicated for manufacture but limits the stability and production. Here, we engineered a series of interchain disulfide bonds in the Fab region of IgG-svFv BsAbs and evaluated its biophysical and biological properties. We found that simultaneously replaced the position of VH44-VL100 and CH1126-CL121 residues with cysteine, to form two additional disulfide bonds, could markedly increase monomeric BsAb formation and yield. The thermostability and stability against aggregation and degradation also performed better than BsAbs without extra disulfide bonds introduction. Besides, the affinity of engineered BsAbs was maintained, and the h8B-BsAb antibody had a slight enhancement in an inhibitory effect on target cells.

scholarly journals 766 Novel bioluminescent bioassays for the discovery and development of T cell redirecting cancer therapies

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A814-A814
Author(s):  
Vanessa Ott ◽  
Julia Gilden ◽  
Jamison Grailer ◽  
Michael Slater ◽  
Pete Stecha ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Lines ◽  
Tumor Antigens ◽  
Cytotoxic T Cells ◽  
Luciferase Reporter ◽  
Target Cells ◽  
Cancer Therapies ◽  
Donor Variability ◽  
T Cell Lines

BackgroundTwo main approaches for T cell-based therapies involve molecular T cell redirection by CD3 bispecific molecules such as bispecific T-cell engagers (BiTE) and cellular T cell redirection by genetic modification of T cells with chimeric antigen receptors (CAR) or transgenic T cell receptors (TCR). BiTEs redirect the cytotoxic activity of endogenous polyclonal T cells by simultaneously engaging CD3 on T cells and tumor antigens on target cells. BiTE potency studies have relied on primary cells, which measure target cell killing through redirected T cell cytotoxicity (RTCC) or cytokine release. However, these primary cell-based assays suffer from high donor-to-donor variability, as well as lengthy and hard to implement protocolsMethodsWe have recently developed a new RTCC assay and cytokine immunoassays that are simple, sensitive and can quantitatively measure the potency of BiTEs and similar biologics. In this assay, preactivated cytotoxic T cells and target cells (both in cryopreserved thaw-and-use format) stably expressing a HaloTag-HiBiT fusion protein are co-incubated with a BiTE, which results in lysis of the target cells and subsequent release of the Halotag-HiBiT protein. These HiBiT proteins then bind to extracellular LgBiT provided in the detection reagent and form functional NanoLuc Luciferase to generate luminescence.ResultsThe assay is homogenous, highly sensitive, and has a robust assay window. Use of CAR-T has demonstrated promising results in treating leukemia, while the development of TCR-engineered T cells that can recognize intracellular tumor antigens, is still in early stages. To facilitate the screening and characterization of new transgenic TCRs, we used CRISPR/Cas9 to develop two TCRaß-null reporter T cell lines, which are CD4+ or CD8+. Reintroduction of peptide-specific TCR a and ß chains into TCRaß-null reporter T cell lines results in peptide-dependent TCR activation and luciferase reporter expression. The select expression of CD4 or CD8 in the TCRaß-null reporter T cell lines can enable the development of transgenic TCRs for both MHCI- and MHCII-restricted tumor antigen targets.ConclusionsTogether, these bioluminescent bioassays represent a new set of tools for the discovery and development of T cell-based immunotherapies.

scholarly journals A modular and controllable T cell therapy platform for acute myeloid leukemia

Leukemia ◽  
2021 ◽  
Author(s):  
Mohamed-Reda Benmebarek ◽  
Bruno L. Cadilha ◽  
Monika Herrmann ◽  
Stefanie Lesch ◽  
Saskia Schmitt ◽  
...  
Keyword(s):  
T Cells ◽  
Acute Myeloid Leukemia ◽  
T Cell ◽  
Cell Therapy ◽  
Myeloid Leukemia ◽  
Tumor Antigens ◽  
Adoptive T Cell Therapy ◽  
Single Chain ◽  
T Cell Therapy ◽  
Acute Myeloid

AbstractTargeted T cell therapy is highly effective in disease settings where tumor antigens are uniformly expressed on malignant cells and where off-tumor on-target-associated toxicity is manageable. Although acute myeloid leukemia (AML) has in principle been shown to be a T cell-sensitive disease by the graft-versus-leukemia activity of allogeneic stem cell transplantation, T cell therapy has so far failed in this setting. This is largely due to the lack of target structures both sufficiently selective and uniformly expressed on AML, causing unacceptable myeloid cell toxicity. To address this, we developed a modular and controllable MHC-unrestricted adoptive T cell therapy platform tailored to AML. This platform combines synthetic agonistic receptor (SAR) -transduced T cells with AML-targeting tandem single chain variable fragment (scFv) constructs. Construct exchange allows SAR T cells to be redirected toward alternative targets, a process enabled by the short half-life and controllability of these antibody fragments. Combining SAR-transduced T cells with the scFv constructs resulted in selective killing of CD33+ and CD123+ AML cell lines, as well as of patient-derived AML blasts. Durable responses and persistence of SAR-transduced T cells could also be demonstrated in AML xenograft models. Together these results warrant further translation of this novel platform for AML treatment.

scholarly journals A scDb-based trivalent bispecific antibody for T-cell-mediated killing of HER3-expressing cancer cells

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Nadine Aschmoneit ◽  
Sophia Steinlein ◽  
Lennart Kühl ◽  
Oliver Seifert ◽  
Roland E. Kontermann
Keyword(s):  
T Cell ◽  
Binding Site ◽  
Cancer Cell ◽  
Cancer Progression ◽  
T Cell Activation ◽  
Cell Activation ◽  
Egf Receptor ◽  
Bispecific Antibodies ◽  
Target Cells ◽  
Single Chain

AbstractHER3 is a member of the EGF receptor family and elevated expression is associated with cancer progression and therapy resistance. HER3-specific T-cell engagers might be a suitable treatment option to circumvent the limited efficacy observed for HER3-blocking antibodies in clinical trials. In this study, we developed bispecific antibodies for T-cell retargeting to HER3-expressing tumor cells, utilizing either a single-chain diabody format (scDb) with one binding site for HER3 and one for CD3 on T-cells or a trivalent bispecific scDb-scFv fusion protein exhibiting an additional binding site for HER3. The scDb-scFv showed increased binding to HER3-expressing cancer cell lines compared to the scDb and consequently more effective T-cell activation and T-cell proliferation. Furthermore, the bivalent binding mode of the scDb-scFv for HER3 translated into more potent T-cell mediated cancer cell killing, and allowed to discriminate between moderate and low HER3-expressing target cells. Thus, our study demonstrated the applicability of HER3 for T-cell retargeting with bispecific antibodies, even at moderate expression levels, and the increased potency of an avidity-mediated specificity gain, potentially resulting in a wider safety window of bispecific T-cell engaging antibodies targeting HER3.

The mechanism of T cell mediated cytotoxicity IV. Studies on communicating junctions between cells in contact

1977 ◽  
Vol 196 (1122) ◽  
pp. 73-84 ◽  
Keyword(s):  
T Cell ◽  
Mammalian Cells ◽  
Cytotoxic T Cells ◽  
Diploid Cell ◽  
Target Cells ◽  
Cytotoxic Lymphocytes ◽  
Communicating Junctions ◽  
Unique System ◽  
Pass Through ◽  
Autoradiographic Technique

A modified autoradiographic technique has been developed which makes it possible to demonstrate the intercellular transfer of diffusible molecules through communicating junctions. This technique has been used to decide whether or not there is a cytoplasmic union between cytotoxic lymphocytes and the target cells they destroy. The transfer of 51 Cr, [ 3 H]uridine and [ 3 H]choline has been demonstrated between human diploid cell line cells (MRC 5) in contact. This has provided a system in which the techniques could be assessed. The demonstration that 51 Cr can pass through communicating junctions provides a unique system for the investigations of these structures. Despite the fact that all three labels could transfer between MRC 5 cells in contact, no transfer between cytotoxic T cells and P815 target cells could be demonstrated during a cytotoxic reaction. The reported transfer of fluorescein can probably be attributed to the transfer of fluorescein ester via the extracellular space. It is concluded, therefore, that communicating junctions of the type that can form between certain mammalian cells in contact do not contribute to the mechanism of T cell cytotoxicity.

Unicar: A Novel Modular Retargeting Platform Technology for CAR T Cells

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5549-5549 ◽  
Author(s):  
Marc Cartellieri ◽  
Simon Loff ◽  
Malte von Bonin ◽  
Elham P. Bejestani ◽  
Armin Ehninger ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Target Cell ◽  
Binding Domain ◽  
Single Chain ◽  
Chain Fragment ◽  
Cell Recruitment ◽  
Single Chain Fragment Variable ◽  
Car T ◽  
Single Chain Fragment

Abstract The adoptive transfer of T cells engineered with chimeric antigen receptors (CARs) is currently considered as a highly promising therapeutic option for treatment of otherwise incurable malignant diseases. CARs combine the cellular and humoral arm of the immune response by assembling a single-chain fragment variable (scFv) as binding moiety which provides the antigen-specificity and an activating immune receptor. It has been demonstrated both in vitro and in vivo, that CAR engrafted effector T cells mediate long-lasting anti-tumor responses. Despite encouraging clinical efficacy targeting CD19 in recent clinical trials, the appearance of potentially life-threatening adverse reactions and the lack of control mechanisms once initiated, prevent more widespread application of the CAR technology. To overcome limitations of conventional CAR T cells, a unique chimeric antigen receptor (UniCAR) technology was developed (Fig. 1) which allows precise control of CAR T cell reactivity, thus lowering the risk of side effects while preserving efficacy. Moreover, the UniCAR technology enables the retargeting of engrafted T cells against more than one antigen simultaneously or subsequently, thus reducing the risk for development of antigen-loss tumor variants under treatment. The UniCAR technology splits the signaling and antigen-binding aspects of conventional CAR into two individual components. T cells are engineered to express a universal CAR (UniCAR), which has specificity for a short peptide motif of 10 amino acids derived from a human nuclear protein. Thus, T cells engineered to express UniCAR remain inactivated after re-infusion, since the UniCAR target is not available for binding under physiological conditions. The ultimate antigen-specificity of the system is provided separately by targeting modules (TMs) comprising a binding domain e.g., a tumor-antigen specific scFv, fused to the nuclear antigen motif recognized by the UniCAR binding domain. Here we provide first in vitro and in vivo prove of concept for this new approach. Antigen-specific redirection of T cells armed with the universal CAR in the presence of different targeting modules against various antigens (CD33, CD123, CD19, CD20, PSCA, PSMA,) was effective at femtomolar concentrations of the targeting module both. Taken together, the modular nature of UniCAR technology will allow retargeting of autologous, patient-derived T cells to several antigens under controlled pharmacological conditions and has the potential to become a highly effective treatment option for late stage cancer patients with reduced risks for side effects. Figure 1. Schematic representation of T cell recruitment with the modular UniCAR system. The UniCAR T cell recruitment system consists of two separated units. The first unit is the UniCAR expressed on T cells with a single-chain fragment variable (scFv) specific for a short 10 aa long peptide motif. The intracellular signalling domain of the UniCAR contains a costimulatory domain derived from CD28 and the T cell receptor z chain. The second unit is a targeting molecule (TM) which consists of a scFv fused to the peptide epitope. The cross-linkage of T cell and target cell is mediated by interaction between the UniCAR binding domain on T cells and target cell binding TM. Figure 1. Schematic representation of T cell recruitment with the modular UniCAR system. / The UniCAR T cell recruitment system consists of two separated units. The first unit is the UniCAR expressed on T cells with a single-chain fragment variable (scFv) specific for a short 10 aa long peptide motif. The intracellular signalling domain of the UniCAR contains a costimulatory domain derived from CD28 and the T cell receptor z chain. The second unit is a targeting molecule (TM) which consists of a scFv fused to the peptide epitope. The cross-linkage of T cell and target cell is mediated by interaction between the UniCAR binding domain on T cells and target cell binding TM. Disclosures Cartellieri: Cellex Patient Treatment GmbH: Employment. Loff:GEMoaB Monoclonals GmbH: Employment. Ehninger:GEMoaB Monoclonals GmbH: Employment, Patents & Royalties: related to the UniTARG system. Ehninger:GEMoaB Monoclonals GmbH: Equity Ownership; Cellex Patient Treatment GmbH: Equity Ownership. Bachmann:GEMoaB Monoclonals GmbH: Equity Ownership, Patents & Royalties: related to the UniTARG system.

Pharmacokinetics (PK) of blinatumomab and its clinical implications.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 3048-3048 ◽  
Author(s):  
Benjamin Wu ◽  
Youssef Hijazi ◽  
Andreas Wolf ◽  
Christian Brandl ◽  
Yu-Nien Sun ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
Lymphoblastic Leukemia ◽  
Leukemia Cell ◽  
Target Cells ◽  
Clinical Implications ◽  
Single Chain ◽  
Disease Heterogeneity ◽  
Kidney Involvement ◽  
All Treatment

3048 Background: Blinatumomab is an investigational, bispecific, single-chain T cell engaging (BiTE) antibody of 55 kD that targets CD19 on B cells and CD3 on T cells. Blinatumomab induces polyclonal T cell activation and proliferation, resulting in redirected lysis of CD19+target cells. Comprehensive analysis of its PK and the clinical implications is presented. Methods: PK data from 131 patients enrolled in 3 phase 1 or 2 studies of non-Hodgkin lymphoma (NHL; N=76), relapsed/refractory acute lymphoblastic leukemia (r/r ALL; N=36), and ALL with minimal residual disease (MRD; N=19) were analyzed. Blinatumomab was given by constant IV (cIV) infusion at 0.5, 1.5, 3, 5, 10, 15, 30, 60 and 90 μg/m2/d over 4 weeks/cycle. Serum blinatumomab concentrations were assessed using a validated bioassay. PK parameters, including volume of distribution (V), half-life (t1/2) and clearance (CL), were analyzed with noncompartmental methods. CL was derived by dividing infusion rate by blinatumomab concentration at steady state (Css). Mean CL from each patient was used to determine disease heterogeneity and for covariate analyses. Effective dose was assessed with PK, in vitroand clinical B cell data. Results: At the doses tested, blinatumomab had linear PK that was stable over time. V (~5 L) approximated that of monoclonal antibodies. Blinatumomab had a t1/2 of ~2 h, with systemic CL of ~2 L/h. Minute blinatumomab concentrations were detected in the urine of 3 (of 13) NHL patients at a dose of 60 μg/m2/d. There was no trend of NHL, r/r ALL or ALL with MRD; CrCL, age, gender, weight, or body surface area (BSA) influencing CL. Preliminary analysis showed comparable mean CL values in patients with CrCL ≥30 mL/min, ranging from 1.9 to 2.6 L/h. To achieve Css above the in vitro EC90 value for leukemia cell lines (470 pg/mL) and complete B cell suppression in patients, 15 μg/m2/d of blinatumomab given as cIV over 4 weeks/cycle is desired for ALL treatment. Conclusions: Blinatumomab PK was linear, stable, and independent of NHL, r/r ALL or ALL with MRD. Kidney involvement in its excretion was limited at the investigated doses. cIV administration is required due to the short t1/2. Flat or BSA-based dosing can be used in adults. A cIV dose of ≥15 μg/m2/d provides adequate exposure for ALL treatment. Clinical trial information: NCT00274742, NCT01209826, NCT00560794.

Antigen-dependent costimulation to improve T-cell therapy for cancer.

2017 ◽  
Vol 35 (7_suppl) ◽  
pp. 151-151
Author(s):  
Christopher C. DeRenzo ◽  
Phuong Nguyen ◽  
Stephen Gottschalk
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Therapy ◽  
Tumor Cells ◽  
T Cell Activation ◽  
Tumor Antigens ◽  
Single Chain ◽  
Antitumor Effects ◽  
T Cell Therapy ◽  
Potential Strategy

151 Background: T-cell therapy for cancer faces several challenges, including limited T-cell expansion at tumor sites, and lack of unique tumor antigens that are not expressed in normal tissues. To overcome the first obstacle, we developed Engager (ENG) T cells, which secrete bispecific molecules consisting of single chain variable fragments specific for CD3 and a tumor antigen. ENG T cells have the unique ability to redirect bystander T cells to tumors, amplifying antitumor effects. Costimulatory chimeric antigen receptors (CoCARs) are one potential strategy to restrict full T-cell activation to tumor sites that express a unique "antigen address." The goal of this project was now to generate T cells that express engager molecules and CoCARs (ENG/CoCAR T cells), which recognize distinct tumor antigens, and evaluate their effector function. Methods: We focused on two tumor antigens, EphA2 and HER2, which are expressed in a broad range of solid tumors. RD114-pseudotyped retroviral particles encoding an EphA2-ENG or a HER2-CoCAR were used to transduce CD3/CD28-activated human T cells. Transduced T cells were cocultured with EphA2+/HER2- or EphA2+/HER2+ tumor cells. Results: Both EphA2-ENG and EphA2-ENG/HER2-CoCAR T cells were activated by EphA2+ targets, as judged by IFNγ secretion. EphA2-ENG T cells secreted little IL-2 and died after one stimulation with EphA2+/HER2- or EphA2+/HER2+ tumor cells. In contrast, EphA2-ENG/HER2-CoCAR T cells secreted high levels of IL-2 and proliferated when stimulated with EphA2+/HER2+ cells. Little IL-2 secretion and no proliferation was observed after stimulation of the same T cells with EphA2+/HER2- cells, indicating these T cells are only fully activated in the presence of both target antigens. Upon repeated stimulation with EphA2+/HER2+ tumor cells, EphA2-ENG/HER2-CoCAR T cells continued to secrete IL-2 and proliferate without the addition of external cytokines for at least 10 weeks. Conclusions: EphA2-ENG/HER2-CoCAR T cells demonstrated robust dual antigen dependent IL-2 secretion, and continued proliferation upon repeat stimulation with EphA2+/HER2+ cells. Thus, providing antigen-specific costimulation is a potential strategy to improve the safety and efficacy of T-cell therapy for cancer.

scholarly journals Specificity of cytotoxicity T cells directed to influenza virus hemagglutinin.

1979 ◽  
Vol 149 (4) ◽  
pp. 856-869 ◽  
Author(s):  
T J Braciale
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cytotoxic T Cells ◽  
Type A ◽  
Cross Reactivity ◽  
Cytotoxic T Cell ◽  
Target Cells ◽  
Effector Cells ◽  
Cell Induction

Purified type A influenza viral hemagglutinin stimulates an in vitro cell-mediated cytotoxic cell response that exhibits a high degree of specificity for the immunizing hemagglutinin. The response magnitude is proportional to the hemagglutinin dose used for stimulation. The lytic activity of the effector cells is H-2 restricted. Analysis of the specificity of the response indicated that these cytotoxic T cells readily distinguish target cells expressing serologically unrelated hemagglutinin from target cells bearing hemagglutinins serologically related to the stimulating hemagglutinin. Further analysis of the fine specificity of cytotoxic T-cell recognition with serologically cross-reactive type A influenza hemagglutinins revealed a hierarchy of cross-reactivity among these hemagglutinins that was the converse of the serologic hierarchy. These results are discussed in terms of possible differences and similarities in the specificity repertoire of cytotoxic T cells and antibodies. Possible implications of these findings from the standpoint of cytotoxic T-cell induction are also discussed.

scholarly journals Tumor-Associated Antigen Presentation by γδ T-Cells in Cancer Immunotherapy

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1411-1411 ◽  
Author(s):  
Anne Marijn Kramer ◽  
Mengyong Yan ◽  
Karl S Peggs ◽  
John Anderson ◽  
Kenth Gustafsson
Keyword(s):  
T Cells ◽  
T Cell ◽  
Tumor Cell ◽  
Antigen Presentation ◽  
Cancer Immunotherapy ◽  
Cytotoxic T Cells ◽  
Γδ T Cells ◽  
Target Cells ◽  
Γδ T Cell ◽  
T Cell Lines

Abstract Tumor-Associated Antigen Presentation by γδ T-Cells in Cancer Immunotherapy Human γδ T-cells are considered to represent a link between innate and adaptive immunity. Their innate killing properties display a potent cytotoxic activity against solid tumors as well as lymphoid and myeloid malignancies. Subsequently, by lysing affected target cells and liberating antigen for uptake, they can differentiate into professional antigen presenting cells (pAPCs) for induction of CD4+ and CD8+ T cell responses. The degree of antigen-specific stimulation of responder T cells is increased in the presence of antibody(Ab)-assisted opsonized target cells, involving the low-affinity receptor for IgG CD16 (Fc γRIII), equivalent to that seen with mature antigen-loaded DCs. To elaborate the implications of this combined killing and pAPC function we have studied how freshly isolated as well as expanded and cloned populations of γδ T-cell subsets kill a target tumor cell, and take up and cross-present tumor-associated antigens (TAA). We performed quantitative analysis on the cellular uptake of different sizes of microspheres, analyzing the correlation between opsonization and internalization. All γδ T-cell subtypes were expanded using artificial APC, engineered to express CD86, CD137L and IL-15, and anti- γδ TCR Ab (B1). Short (EAAGIGILTV) and long (GHSYTTAEEAAGIGILTVILGVLLL) MART-1 peptides were used as antigens for γδ T-cell presentation to MART-1 TCR-transduced cytotoxic T-cells. A CFSE assay was performed to assess cytotoxic T-cell proliferation. Target cells and polysterene microspheres were opsonized with human anti-CD20 IgG1, Rituximab (RTX). CD16 function was blocked with a mouse monoclonal IgG1 anti-CD16 blocking Ab (clone LNK16). Imaging flowcytometry allowed us to quantify internalization of FITC-labeled microspheres. The Internalization Score is defined as the ratio of intensity inside the cell to the intensity of the entire cell. Both γδ T-cell lines and expanded γδ T-cell clones cultured long-term, remarkably, retain both tumor cell killing and take up tumor cell lysates or long synthetic TAA peptides and cross-present these on MHC class I to CD8+ cytotoxic T-cells in a dynamic, controllable fashion, dependent on Ab-opsonization. (Figure 1). The Ab-opsonization of 1 µm microspheres correlates with a higher receptor-mediated phagocytic uptake, in a CD16 dependent manner (Figure 2). The opsonization of 0,5 µm microspheres led to clumping of the microspheres, accounting for the lower uptake in this particular subgroup. For a lack of better alternative, moDCs have been widely used in experimental immunotherapy settings. The ease of manipulation of human γδ T-cells, the ability to be expanded ex-vivo combined with antigen presentation makes them a great potential tool for immunotherapy as a complementary or integrative strategy. Ligation of the γδ T-cell receptor at the tumor site will activate their expansion and innate killing. Yet, antigen presentation will only occur after binding of an immunoglobulin to the tumor cell, thereby activating their dual role. Our goal is to define an effective adjuvant vaccine formulation for inducing leukemia-specific cytolytic effects. We are currently investigating whether γδ T-cells can directly present and/or cross-present to cytotoxic T-cells in-vivo in a humanized mouse model. We believe that the uptake of microspheres by γδ T-cells has an impact on the development of vaccination strategies for cancer immunotherapy, as the immunization of γδ T-cells is a powerful method for the induction or reactivation of cytotoxic T cell specific responses. FIGURE 1 CFSE assay of γδ T-cell lines cross-presenting short and long MART-1 peptides to MART-1 TCR-transduced cytotoxic T-cells in a dynamic, controllable fashion, dependent on Ab-opsonization FIGURE 1. CFSE assay of γδ T-cell lines cross-presenting short and long MART-1 peptides to MART-1 TCR-transduced cytotoxic T-cells in a dynamic, controllable fashion, dependent on Ab-opsonization FIGURE 2a FIGURE 2a. FIGURE 2b FIGURE 2b. Disclosures No relevant conflicts of interest to declare.

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