In vitro analysis of the proliferative potential of T cells from patients with brain tumor: glioma-associated immunosuppression unrelated to intrinsic cellular defect

1992 ◽  
Vol 76 (2) ◽  
pp. 251-260 ◽  
Author(s):  
Daniel W. McVicar ◽  
Donna F. Davis ◽  
Randall E. Merchant
Keyword(s):  
T Cells ◽  
Brain Tumor ◽  
T Cell ◽  
Normal Control ◽  
Phorbol Ester ◽  
Cell Populations ◽  
Glial Tumors ◽  
Control Subjects ◽  
Steroid Dependent

✓ Patients harboring a malignant brain tumor have been described as being highly immunosuppressed, as evidenced by reduced numbers of T cells and the decreased ability of their lymphocytes to produce interleukin-2 (IL-2). In order to determine whether an intrinsic abnormality exists in the T lymphocytes of glioma patients and to evaluate what role corticosteroids may play in glioma-associated immunosuppression, in vitro T cell proliferative function in the presence of recombinant IL-2 (rIL-2) was examined in age-matched groups of normal control subjects, steroid-free patients with glial tumors, steroid-dependent patients with glial tumors, and steroid-dependent patients with nonglial cerebral tumors. The results demonstrated that, when enriched T cell populations of all brain-tumor patients were stimulated with rIL-2 and phytohemagglutinin (PHA), there were no statistically significant differences between any groups. In contrast, when T cell populations were stimulated with mitogenic combinations of phorbol ester, calcium ionophore, and rIL-2, those from steroid-dependent patients with glial tumors had a significantly lower response than those from normal control subjects, suggesting that a population of T cells capable of responding to phorbol ester/ionomycin and not PHA stimulation is inhibited by corticosteroid therapy in glioma patients. In addition, T cells of four brain-tumor patient/age-matched control subject pairs were stimulated with either phorbol ester/ionomycin or PHA for 24 hours; three of the four patients expressed low-affinity IL-2 receptor levels as high or higher than their respective control subjects, suggesting that IL-2 receptor expression in these patients may be quantitatively normal once the T cell number is corrected. Taken together, these results show that the decreased PHA responsiveness that has been previously reported in lymphocytes of glioma patients is not due to a cellular abnormality within the potentially responsive cells, but rather reflects the reduced proportion of T cells within their peripheral blood which, as a consequence, reduces the level of IL-2 production attained upon activation.

scholarly journals Anti-CD20 therapy depletes activated myelin-specific CD8+T cells in multiple sclerosis

2019 ◽  
Vol 116 (51) ◽  
pp. 25800-25807 ◽  
Author(s):  
Joseph J. Sabatino ◽  
Michael R. Wilson ◽  
Peter A. Calabresi ◽  
Stephen L. Hauser ◽  
Jonathan P. Schneck ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
T Cells ◽  
T Cell ◽  
Ex Vivo ◽  
Antibody Therapy ◽  
Myelin Proteins ◽  
T Cell Epitopes ◽  
Control Subjects ◽  
Anti Cd20

CD8+T cells are believed to play an important role in multiple sclerosis (MS), yet their role in MS pathogenesis remains poorly defined. Although myelin proteins are considered potential autoantigenic targets, prior studies of myelin-reactive CD8+T cells in MS have relied on in vitro stimulation, thereby limiting accurate measurement of their ex vivo precursor frequencies and phenotypes. Peptide:MHC I tetramers were used to identify and validate 5 myelin CD8+T cell epitopes, including 2 newly described determinants in humans. The validated tetramers were used to measure the ex vivo precursor frequencies and phenotypes of myelin-specific CD8+T cells in the peripheral blood of untreated MS patients and HLA allele-matched healthy controls. In parallel, CD8+T cell responses against immunodominant influenza epitopes were also measured. There were no differences in ex vivo frequencies of tetramer-positive myelin-specific CD8+T cells between MS patients and control subjects. An increased proportion of myelin-specific CD8+T cells in MS patients exhibited a memory phenotype and expressed CD20 compared to control subjects, while there were no phenotypic differences observed among influenza-specific CD8+T cells. Longitudinal assessments were also measured in a subset of MS patients subsequently treated with anti-CD20 monoclonal antibody therapy. The proportion of memory and CD20+CD8+T cells specific for certain myelin but not influenza epitopes was significantly reduced following anti-CD20 treatment. This study, representing a characterization of unmanipulated myelin-reactive CD8+T cells in MS, indicates these cells may be attractive targets in MS therapy.

Transduction of Malignant Plasma Cells with Three Costimulatory Molecules (TRICOM) Elicits Myeloma-Specific Immune Response in Vitro – a Promising Strategy for Immunotherapy

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1908-1908
Author(s):  
Katarina Luptakova ◽  
Heidi Mills ◽  
Jacalyn Rosenblatt ◽  
Dina Stroopinsky ◽  
Turner Kufe ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
T Cells ◽  
T Cell ◽  
Mononuclear Cells ◽  
Plasma Cells ◽  
Costimulatory Molecules ◽  
Cell Populations ◽  
Autologous Tumor

Abstract Abstract 1908 Introduction: Tumor vaccines hold promise as a means of eliciting anti-myeloma immunity and controlling disease that may be resistant to chemotherapy and biologic therapy. We have developed a whole cell tumor vaccine, whereby patient derived plasma cells are transduced with an attenuated vaccinia vector that contains transgenes for the costimulatory molecules B7.1 (CD80), ICAM-1 (CD54), and LFA-3 (CD58), designated TRIad of COstimulatory Molecules (TRICOM). In this manner, a broad array of tumor antigens, including those which may be specific to a given patient, are presented in the context of costimulatory molecules that have been shown to be synergistic in the stimulation of the effector T-cells. In the present study, we evaluated the phenotype and functional characteristics of TRICOM transduced primary myeloma cells. Methods and results: Plasma cells were isolated from bone marrow aspirates obtained from patients with multiple myeloma following Ficoll density centrifugation. Bone marrow derived mononuclear cells were infected with a replication-defective poxviral vector, the modified vaccinia Ankara strain (MVA), encoding TRICOM, or a control empty MVA vector. The expression of costimulatory molecules was assessed using flow cytometric analysis 3 hrs following viral infection. Viral transduction using the TRICOM vector at the dose of 20 MOI (multiplicity of infection) increased the mean percentage of CD38+ cells expressing CD80, CD54 and CD58 from a minimal baseline level (below 5%) to 70%, 56% and 47%, respectively (n=4). Transduction with control MVA vector did not augment expression of costimulatory molecules on plasma cells (mean percent expression of CD80, CD54 and CD58 of 2.6%, 2.7% and 3.8%, respectively, n=4). Of note, compared to CD38+ plasma cells, the CD38 negative fraction of bone marrow derived mononuclear cells demonstrated a significantly lower TRICOM transduction efficiency (mean percent expression of CD80, CD54 and CD58 of 16%, 17% and 16%, respectively, n=4, p<0.05 compared to CD38+ plasma cells). The ability of MVA-TRICOM transduced plasma cells to stimulate autologous T cell populations in vitro was assessed. Patient derived T-cells were purified from the non-adherent portion of PBMC by magnetic bead separation. MVA-TRICOM or empty MVA vector infected plasma cells were irradiated with 20Gy and co-cultured with autologous T cells at a 10:1 ratio of effector cells to vaccine for 7 days. MVA-TRICOM transduced plasma cells potently stimulated activated T cell responses, as assessed by the percentage of CD4+/CD25+/CD69+ T-cells (mean 7.8% of activated T-cells with TRICOM vaccine vs. 2.7% with control vaccine, n=3, p<0.05). In contrast, vaccine stimulation did not result in regulatory T-cell expansion, assessed as the percentage of cells co-expressing CD4,CD25 and FoxP3 (2.4% vs. 2.3%, for TRICOM and control vaccine, respectively, n=3). In concert with these findings, vaccine stimulation resulted in a polarization towards Th1 cytokine secretion, with 7.9% of CD4+ T-cells expressing intracellular IFN-γ after stimulation with TRICOM vaccine as compared to 5.4% after stimulation with the control vaccine (n=3, p<0.05). To further assess the expansion of tumor specific T cell populations, the ability of vaccine stimulated T cells to kill autologous tumor was assessed in a cell-based fluorogenic cytotoxicity assay. MVA-TRICOM transduced plasma cells potently stimulate the expansion of myeloma specific CTLs with the capacity to lyse autologous tumor targets. Mean CTL lysis was 20% and 8% for vaccine stimulated and unstimulated T cells respectively (n=2). Conclusions: Malignant plasma cells transduced with MVA-TRICOM strongly express costimulatory molecules, and potently stimulate activated, tumor reactive T cell populations. This preclinical data serves as a platform for developing a phase 1 clinical trial evaluating the use of MVA-TRICOM transduced autologous plasma cells in patients with multiple myeloma. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Functional Avidity: A Measure to Predict the Efficacy of Effector T Cells?

2012 ◽  
Vol 2012 ◽  
pp. 1-14 ◽  
Author(s):  
Selena Viganò ◽  
Daniel T. Utzschneider ◽  
Matthieu Perreau ◽  
Giuseppe Pantaleo ◽  
Dietmar Zehn ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Response ◽  
Cell Populations ◽  
High Avidity ◽  
Chronic Infections ◽  
Functional Avidity ◽  
Cognate Antigen

The functional avidity is determined by exposing T-cell populationsin vitroto different amounts of cognate antigen. T-cells with high functional avidity respond to low antigen doses. Thisin vitromeasure is thought to correlate well with thein vivoeffector capacity of T-cells. We here present the multifaceted factors determining and influencing the functional avidity of T-cells. We outline how changes in the functional avidity can occur over the course of an infection. This process, known as avidity maturation, can occur despite the fact that T-cells express a fixed TCR. Furthermore, examples are provided illustrating the importance of generating T-cell populations that exhibit a high functional avidity when responding to an infection or tumors. Furthermore, we discuss whether criteria based on which we evaluate an effective T-cell response to acute infections can also be applied to chronic infections such as HIV. Finally, we also focus on observations that high-avidity T-cells show higher signs of exhaustion and facilitate the emergence of virus escape variants. The review summarizes our current understanding of how this may occur as well as how T-cells of different functional avidity contribute to antiviral and anti-tumor immunity. Enhancing our knowledge in this field is relevant for tumor immunotherapy and vaccines design.

PS2 - 172 Preclinical Validation of a Novel CD33/CD3 Bispecific T-Cell Engager (BiTE) Antibody to Target Patient-Derived Glioblastoma Cells

2016 ◽  
Vol 43 (S4) ◽  
pp. S13-S14
Author(s):  
P. Vora ◽  
C. Venugopal ◽  
C. Choksi ◽  
M. Qazi ◽  
J. Adams ◽  
...  
Keyword(s):  
T Cells ◽  
Brain Tumor ◽  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Adult Brain ◽  
Poor Overall Survival ◽  
Bispecific T Cell Engager ◽  
Bite Antibody

Glioblastoma (GBM), an aggressive primary adult brain tumor, is feared for its near uniformly fatal prognosis. Despite the use of aggressive treatment including surgical resection, radiotherapy and chemotherapy, the outcome of patients with GBM has failed to improve significantly. Numerous studies have implicated CD133+GBM subpopulation as driver of chemo- and radio-resistance. CD133 expression correlates with disease progression, recurrence, and poor overall survival of GBM patients. Here, we describe the preclinical evaluation of a recombinant CD133xCD3 bispecific T-cell engager (BiTE) antibody that redirects human polyclonal T cells to CD133+GBM cells, inducing very potent anti-tumor response. CD133-specific BiTE was constructed; with one arm recognizing the tumor antigen (CD133) while the second is specific to CD3 antigen. Using CD133high and CD133low primary GBM lines, we validated the binding of BiTEs to CD133+GBMs and CD3+T cells. In order to test the ability of BiTEs to functionally elicit CD133-specific cytotoxic responses in vitro, we performed killing assays. We observed CD133-specific BiTE mediated T cell activation and redirection to kill CD133-expressing GBM cells in a co-culture of T cells and GBM cells. The killing was more efficient in CD133high GBMs compared to CD133low GBMs, validating its specificity to target CD133+BTICs. Treatment with BiTEs yielded significant reductions in brain tumor burden in vivo. These data offers compelling evidence that BiTE-mediated cytotoxicity against treatment-resistant CD133+GBMs could provide a very potent, specific and can be a novel therapeutic strategy for GBM patients.

scholarly journals Determinants of in vitro expansion of different human virus-specific FoxP3+ regulatory CD8+ T cells in chronic hepatitis C virus infection

2009 ◽  
Vol 90 (7) ◽  
pp. 1692-1701 ◽  
Author(s):  
Eva Billerbeck ◽  
Nobuhiro Nakamoto ◽  
Bianca Seigel ◽  
Hubert E. Blum ◽  
Kyong-Mi Chang ◽  
...  
Keyword(s):  
T Cells ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
T Cell ◽  
Cell Populations ◽  
Antigen Specificity ◽  
Specific Stimulation ◽  
Differentiation Status ◽  
Antigen Presenting

It has been shown previously that suppressive virus-specific FoxP3+ regulatory CD8+ T cells can be expanded from human peripheral blood mononuclear cells after in vitro antigen-specific stimulation. This study extended this finding by analysing the mechanisms of virus-specific FoxP3+ regulatory CD8+ T-cell generation during peptide-specific expansion in vitro. It was shown that hepatitis C virus (HCV)-, influenza virus (FLU)-, Epstein–Barr virus (EBV)- and cytomegalovirus (HCMV)-specific FoxP3+ regulatory CD8+ T cells could be expanded differentially from the blood of chronically HCV-infected patients following in vitro peptide-specific stimulation. The different ability of virus-specific CD8+ T-cell populations to express FoxP3 after continuous antigen stimulation in vitro correlated significantly with the ex vivo differentiation status. Indeed, CD27+ CD28+ CD57− HCV-, FLU- and EBV-specific CD8+ T cells displayed a significantly higher ability to give rise to FoxP3+ regulatory CD8+ T cells compared with CD27− CD28− CD57+ HCMV-specific CD8+ T cells. Similar T-cell receptor expression patterns of FoxP3+ versus FoxP3− CD8+ T cells of the same antigen specificity indicated that both cell populations were probably expanded from the same virus-specific CD8+ T-cell precursor. In addition, no specific antigen-presenting cell populations were required for the generation of FoxP3+ CD8+ T cells, as CD8+-selected virus-specific FoxP3+ CD8+ T cells could be expanded by peptide presentation in the absence of antigen-presenting cells. Taken together, these results suggest that the ability to expand FoxP3+ regulatory CD8+ T cells from virus-specific CD8+ T cells differs among distinct virus-specific CD8+ T-cell populations depending on the differentiation status.

scholarly journals Tetramer Enrichment Reveals the Presence of Phenotypically Diverse Hepatitis C Virus-Specific CD8+T Cells in Chronic Infection

2014 ◽  
Vol 89 (1) ◽  
pp. 25-34 ◽  
Author(s):  
Katja Nitschke ◽  
Tobias Flecken ◽  
Julia Schmidt ◽  
Emma Gostick ◽  
Matthias Marget ◽  
...  
Keyword(s):  
T Cells ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
T Cell ◽  
Mhc Class I ◽  
Class I ◽  
Effector Memory ◽  
Cell Populations ◽  
Memory Phenotype

ABSTRACTVirus-specific CD8+T cells are rarely detectableex vivoby conventional methods during chronic hepatitis C virus (HCV) infection. In this study, however, we were able to detect and characterize HCV-specific CD8+T cells in all chronically HCV genotype 1a-infected, HLA-A*02:01-positive patients analyzed by performing major histocompatibility complex (MHC) class I tetramer enrichment. Two-thirds of these enriched HCV-specific CD8+T-cell populations displayed an effector memory phenotype, whereas, surprisingly, one-third displayed a naive-like phenotype despite ongoing viral replication. CD8+T cells with an effector memory phenotype could not expandin vitro, suggesting exhaustion of these cells. Interestingly, some of the naive-like CD8+T cells proliferated vigorously uponin vitropriming, whereas others did not. These differences were linked to the corresponding viral sequences in the respective patients. Indeed, naive-like CD8+T cells from patients with the consensus sequence in the corresponding T-cell epitope did not expandin vitro. In contrast, in patients displaying sequence variations, we were able to induce HCV-specific CD8+T-cell proliferation, which may indicate infection with a variant virus. Collectively, these data reveal the presence of phenotypically and functionally diverse HCV-specific CD8+T cells at very low frequencies that are detectable in all chronically infected patients despite viral persistence.IMPORTANCEIn this study, we analyzed CD8+T-cell responses specific for HLA-A*02:01-restricted epitopes in chronically HCV-infected patients, using MHC class I tetramer enrichment. Importantly, we could detect HCV-specific CD8+T-cell populations in all patients. To further characterize these HCV-specific CD8+T-cell populations that are not detectable using conventional techniques, we performed phenotypic, functional, and viral sequence analyses. These data revealed different mechanisms for CD8+T-cell failure in HCV infection, including T-cell exhaustion, viral escape, and functional impairment of naive-like HCV-specific CD8+T cells.

Clinical Significance of Free Circulating CD3 and CD5 in Patients with Chronic Lymphocytic Leukemia.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4947-4947
Author(s):  
Menna Hodge ◽  
Susan O’Brien ◽  
Adam Abdool ◽  
Michael Keating ◽  
Iman Jilani ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cells ◽  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
Normal Control ◽  
Cell Receptor ◽  
Lymphocytic Leukemia ◽  
Β2 Microglobulin ◽  
Control Subjects

Abstract &lt;/DEL&gt; CD5, a transmembrane protein expressed in T-cells, few B-cells, and chronic lymphocytic leukemia (CLL) B-cells, is the ligand for CD72 and may play a role in B-cell-T-cell communication. CD5 is part of the T-cell receptor (TCR)-CD3 complex in T-cells as well as the B-cell receptor (BCR) complex and serves as substrate for induction of tyrosine kinase activity. Since leukemic cells have high turnover and pour their protein, RNA, and DNA into the circulation, we speculated that free circulating CD3 (cCD3) and CD5 (cCD5) could be detected in the plasma of patients with CLL. We have developed a bead-based sandwich immunoassay to measure cCD3 and cCD5 in the plasma. Using this assay, we assessed the value of cCD5 measurement, alone and after normalization to cCD3 levels, as a tumor marker in CLL. Plasma levels of cCD3 and cCD5 were measured in 85 patients with CLL and 51 normal control subjects. cCD3 and cCD5 levels were significantly higher in patients with CLL (median, 7,465 and 55,806 U/μl, respectively) than in normal control subjects (median, 830 and 1,671 U/μl, respectively). Patients with CLL had significantly higher cCD5:cCD3 ratios (median, 5.28; range, 0–161) than did normal controls (median, 1.70; range, 0–8.06) (P &lt;0.0001). Levels of cCD5, but not cCD3, correlated positively with WBC count, β2-microglobulin level, splenomegaly, and Rai stage (all P &lt;0.01). The cCD5:cCD3 ratio also correlated with Rai stage (P = 0.04) and β2-microglobulin level (P = 0.03). cCD5 levels and the cCD5:cCD3 ratio both correlated with survival (P = 0.03). These findings confirm that free circulating surface markers can be detected in the circulation of patients with CLL, most likely reflect the tumor load, and can be used as tumor markers. The biological and therapeutic relevance of these free circulating proteins should be considered in pharmacokinetic and pharmacodynamic studies.

Alloreactive T Cell Clonotypes Identified By In Vitro Mixed Lymphoid Reaction and High-Throughput Sequencing Exhibit Increased Frequency In Peripheral Blood Samples From Patients Following Allogeneic Hematopoietic Cell Transplantation For Chronic Lymphocytic Leukemia

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 149-149
Author(s):  
Aaron C. Logan ◽  
Mark R. Krampf ◽  
Mark Klinger ◽  
Martin Moorhead ◽  
Jianbiao Zheng ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Research Funding ◽  
High Throughput Sequencing ◽  
Hematopoietic Cell Transplantation ◽  
Lymphocytic Leukemia ◽  
Cell Populations ◽  
Blood Samples ◽  
Donor T Cells

Abstract Introduction Allogeneic hematopoietic cell transplantation (allo-HCT) provides long-term immunologic disease control for a substantial portion of patients with hematologic malignancies. Chronic lymphocytic leukemia (CLL) is sensitive to graft-versus-leukemia (GVL) effects as evidenced by responses to reduced-intensity conditioning (RIC) allo-HCT, and to donor lymphocyte infusions (DLI) for post-HCT relapse. To identify potential alloreactive (AR)/GVL T cells, we performed in vitro mixed lymphocyte reactions (MLRs) between recipient CLL cells and donor T cells derived from blood apheresis products acquired for DLI. Responder and non-responder T cell populations from MLRs and recipient post-HCT blood samples underwent T cell receptor beta (TCRB) high-throughput sequencing (HTS). The prevalence of candidate AR/GVL TCRB clonotypes at various times following HCT was quantified and correlated with CLL disease burden and graft-versus-host disease (GVHD). Methods CLL cells isolated from cryopreserved PBMC aliquots of 7 patients who experienced post-HCT relapse were pre-stimulated in vitro for 72 hours with CpG oligodeoxynucleotides in X-VIVO 15 supplemented with IL-4, IL-7, BAFF, and GM-CSF. Upregulation of CD80, CD86, CD40L, MHCI, and/or MHCII was confirmed by flow cytometry. Donor T cells were isolated from cryopreserved DLI using pan-T cell isolation beads (Miltenyi), labeled with CFSE, and incubated with CpG-stimulated CLL cells for 7 days. Upon the conclusion of the MLR incubation, T cell populations were sorted into rapid responders (RR; CFSEdim), slow responders (SR; CFSEbrightCD69pos) and non-responders (NR; CFSEbrightCD69neg) and RNA was isolated from each cell population. RNA was then amplified and TCRB sequenced using the LymphoSIGHT platform (Sequenta). PBMC samples collected and cryopreserved pre-HCT and regularly following HCT and DLI were also subjected to TCRB-HTS. Results RR cells comprised 11.5 +/- 9.2% of MLR T cells, whereas SR were 4.2 +/- 3.5% and NR were 84.3 +/- 10.1% (Fig 1A). RR, SR, and NR populations demonstrated clonotypic exclusion with a mean 4.4% +/- 5.5% coincidence between populations (Fig 1B). TCRB diversity in the RR population was more restricted compared with diversity in the SR and NR populations, with the mean number of clonotypes comprising the top 50th percentile of total TCRB reads being 11.8 +/- 6.5%, 17.7 +/- 8.5%, and 20.2 +/- 1.8% of unique reads, respectively (p<0.01). Candidate AR/GVL TCRB clonotypes, specified as those enriched in MLR-responder populations compared to pre-stimulation samples, were validated by comparison with pre-stimulation frequency-matched clonotypes. The mean frequency of AR/GVL TCRB clonotypes in blood samples post-HCT were 10- to 100-fold greater than control clonotypes, depending on the patient (Fig 1C). AR/GVL T cells were present within the post-HCT PBMC TCRB repertoires at mean frequencies of 5x10-4 at day +90 rising to 2x10-3 by day +360 post-HCT in 3/4 patients experiencing at least 2 year remissions post-HCT. In patients experiencing early relapse (within 1yr post-HCT), no candidate AR/GVL clonotypes were identified in 1/3 patients and 2/3 exhibited AR/GVL clonotypes at roughly one log lower frequencies (mean 8x10-5 at day +90 and 4x10-4 at day 360) than those with longer remissions (Fig 1D). One patient who experienced fatal post-DLI steroid-refractory GVHD exhibited striking changes in AR/GVL clonotype prevalence following DLI (Fig 1D). Conclusions In vitro MLR between donor T cells and CpG-stimulated CLL cells selects clonotypically distinct T cell populations with an oligoclonal RR population. Persistence of adoptively transferred candidate AR/GVL clones identified by MLR appears to correlate with likelihood of maintaining clinical remission beyond 2 years in CLL patients undergoing RIC allo-HCT. Failure to adoptively transfer AR/GVL clonotypes may be associated with early treatment failure. Disclosures: Klinger: Sequenta, Inc.: Employment, Research Funding. Moorhead:Sequenta, Inc.: Employment, Research Funding. Zheng:Sequenta, Inc.: Employment, Research Funding. Faham:Sequenta Inc.: Employment, Stockholder Other.

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