New Xenograft Method For Studying Leukemia and Drug Response In Turkey Embryos

Abstract Background A widely accepted in vivo model for studying leukemia and its treatment is the highly immune-deficient mice NOD/SCID (b2M-/- or rag-/-). While this model is powerful and recapitulates the phenotypes of blood malignancies in vivo. it is costly and complex, requiring 1-2 months to establish engraftment and the mice are susceptible to spontaneous neoplasms. For these and other reasons the testing of new drugs on leukemia is primarily performed in vitro. The development of antileukemia therapies could be facilitated by a rapid and cost-effective in vivo system for evaluating human leukemia growth and its response to new drugs. Additionally, the treatment of relapsed or refractory disease could be individually tailored by this rapid and cost-effective in vivo system by evaluating patient's cells response to new agents. Turkey embryos are inexpensive, require no maintenance, are larger than chicks are more easily manipulated and have a more robust engraftment (Grinberg I, et al, Leuk Res, 2009; 33:1417-26). We recently described this new in-vivo system for studying multiple myeloma in the pre-immune turkey embryo (Farnoushi, Y., et al.,Br J Cancer, 2011; 105:1708-18). We now demonstrate application of this rapid alternative xenograft system for the preclinical assessment of leukemia growth and therapy. Methods BCR/Abl+ human leukemia lines K562 or LAMA-84 c-Kit+ CHRF 4288 and fresh patient cells were injected into turkey egg chorioallantoic membrane (CAM) veins. Cell injections were performed on day embryonic day E11as previously optimized (Farnoushi, Y., et al.,as above). To determine the engraftment of human AML cells on E19-23, in hematopoietic tissue, the engraftment of human AML cells in the BM was detected in BM by flow cytometry (FC) using anti-human CD71 for LAMA and K562, anti- human CD33 for CHRF and fresh leukemia samples. Engraftment in bone marrow (BM) and other organs was also monitored using Quantitive real time PCR (Q-PCR) comparing the amount of genomic human to the amount of avian DNA and number of human cells / avian cells in BM. Drug response was tested by IV injection of therapeutic range doses of Imatinib (Glivec ®) and Doxorubicin, 48H after cell grafting, at drug levels precalibrated to be non-toxic to the developing embryo by LD50 and BM cell viability compared to control. Six days later (E19) the embryos were sacrificed and the BM collected for FC and hematopoietic and non-hematopoietic tissues for molecular analysis. Results The optimal treatment and readout times were resolved by injecting cells on E11 and determining the kinetics of leukemia cell engraftment in the BM on E15, E18, and E23 in BM and liver. The highest engraftment level in the BM bone marrow (BM) and liver of lines tested was detected at E18 by Q-PCR, and FC in more than 90% of the injected embryos. The average engraftment (±s.d.) in the BM after one week was 4.6%+0.75 K562, 5.16%+2.15 LAMA-84, 7.65%+1.15 CHRF-4288 ( n=7-12 per group) and 2.5% fresh leukemia cells was detected by FC. Q-PCR results were similar to those of FC. Imatinib toxicity testing revealed 100% survival of embryos with no BM toxicity on embryos treated on E13 with doses similar to a human therapeutic dose, up to 0.75 mg/egg. Treatment of embryos with 100 ug Doxorubicin was previously shown to be not toxic to the embryos (Taizi M et al. Exp Hematol 2006; 34:1698–708). A single dose of 0.75 mg Imatinib/embryo dramatically reduced engraftment in BM and several other organs of all 3 AML cell lines or fresh patient leukemia cells. A similar effect was also obtained by a single dose Rx 100ug Doxorubicin. Treatment of a single dose of 0.75 Imatinib mg/embryo 48H after injecting ARH-77 (multiple myeloma) had no effect on cell engraftment. Treatment with a single non toxic dose of Revlimid as previously described (Farnoushi, Y., et al. as above) eliminated engraftment of ARH77 cells, clearly demonstrating the specificity of the drug treatments. Conclusions The results presented demonstrate the potential utility of a practical avian embryo model for testing drug activity in vivo. With further work the turkey embryo may provide a new xenograft in vivo method for studying the biology of leukemia engraftment, and for rapidly and affordably testing leukemia therapies. This system may provide a new platform for developing individualized patient screening for response or resistance to particular therapeutic agents. Disclosures: No relevant conflicts of interest to declare.

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Adipocytes Secrete Factors That Cause Leukemia Drug Resistance.

Blood ◽

10.1182/blood.v112.11.1346.1346 ◽

2008 ◽

Vol 112 (11) ◽

pp. 1346-1346

Author(s):

James W Behan ◽

Jason P Yun ◽

Marina P Proektor ◽

Ehsan A Ehsanipour ◽

Anna Butturini ◽

...

Keyword(s):

Bone Marrow ◽

Chemotherapy Resistance ◽

Leukemia Cell ◽

Conditioned Media ◽

Leukemia Cells ◽

Cell Contact ◽

Human Leukemia ◽

Bone Marrow Niche

Abstract We have previously shown that obesity is an independent predictor of leukemia relapse in children. We have also shown that obese mice transplanted with syngeneic leukemia cells have poorer survival after chemotherapy, even when they are dosed proportional to body weight. Since interactions between leukemia cells and cells of the bone marrow niche are considered important for chemotherapy resistance and relapse, and adipocytes can comprise ~50% of the bone marrow niche, we developed in vivo and in vitro models to investigate the role of adipocytes in the leukemia microenvironment. Obese C57Bl/6J mice were transplanted with GFP+ murine preB cell ALL (“8093”) cells and then treated with vincristine (0.5 mg/kg/week × 3 weeks). At the time of relapse, we found that GFP+ leukemia cells persisted in the fat pads of the mice. We then developed an in vitro co-culture system in which human or murine leukemia cells were cultured together with adipocytes (differentiated 3T3-L1s). Undifferentiated 3T3-L1 cells, which are fibroblastic in nature, were used as a control. In this model, adipocytes severely diminished the anti-leukemic effect of all chemotherapeutics tested against murine 8093 cells, including vincristine, dexamethasone, nilotinib, daunorubicin, and L-asparaginase. Adipocytes also protected murine T-cell ALL and human SD-1, RCH-ACV, and BV173 cells from vincristine and daunorubicin. Adipocyte protection of leukemia cells occurred independent of cell contact. Further experiments demonstrated that media conditioned by adipocytes was able to protect 8093 cells from a 3-day exposure to 25 nM dexamethasone (viable cells were at 40±12% of their plated value in regular media, 66±17% in fibroblast-conditioned media, and 109±24% in adipocyte-conditioned media, p<0.05). Surprisingly, adipocyte-conditioned media did not protect leukemia cells from daunorubicin. However, media conditioned by the presence of both adipocytes and leukemia cells simultaneously conferred a high degree of resistance to the leukemia cells (n=3, p<0.05 compared to all other media types). In summary, adipose tissue is a reservoir for relapsed leukemia cells in vivo. Adipocytes engender protection from multiple chemotherapies in murine and human leukemia cell lines. Adipocytes secrete factor(s) that confer dexamethasone and daunorubicin resistance to leukemia cells, though for the latter drug it appears that a two-way communication between leukemia and adipocytes may be necessary for this protection. Figure Figure

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Leukemia Cell Xenograft in Ovo Enables Real-Time Testing of Response to Therapy

Blood ◽

10.1182/blood.v126.23.3781.3781 ◽

2015 ◽

Vol 126 (23) ◽

pp. 3781-3781

Author(s):

Varda Deutsch ◽

Sigi Kay ◽

Hila Jan ◽

Ben Zion Katz ◽

Michal Cipok

Keyword(s):

Real Time ◽

Drug Response ◽

Leukemia Cell ◽

Therapeutic Agents ◽

Human Leukemia ◽

In Ovo ◽

Cell Injection ◽

Raji Cells ◽

Cell Engraftment

Abstract Background: Acute myeloid leukemia (AML) is most common in people over the age of 60 where it remains an almost incurable malignancy with a grim prognosis. Evaluation of new therapeutic agents in vitro and in vivo is critical for drug development, yet there are few in-vivo models for studying human leukemia and its therapy. The best model used is the high cost immune-deficient mice and that require several weeks to assess drug response. To complicate matters, AML almost certainly relapses with cells that are not necessarily exactly identical to the original malignant clone, often limiting therapeutic options. The development of anti-leukemia therapies could be facilitated by a rapid and cost effective in vivo system for evaluating response to new drugs. Additionally, decisions regarding personalized treatment for relapsed or refractory leukemia patients must be rapid, and produce results within several days, as longer time periods can be detrimental. Herein, we describe a fast, economical, in ovo turkey embryo model, which provides a unique system to meet these requirements. The model can be used for the assessment of human leukemia infiltration in medullary and extramedullary tissues and more importantly for rapid testing of anti- leukemic agents within the bone marrow (BM). This system can be applied for new drug development and for personalized real time response of patient cells to potential leukemia therapies. Methods: BCR/Abl+ AML lines K562 and LAMA-84 , c-Kit+ CHRF-4288, fresh AML patient and Raji Burkit lymphoma cells (5x106) were injected into turkey egg chorioallantoic membrane (CAM) veins on embryonic day E11 previously optimized (1). Engraftment in BM was detected by flow cytometry (FC) using anti-human CD71 or anti- human CD33 for AML and anti human CD45 for Raji cells, or by Quantitative real time PCR (Q-PCR) comparing the amount of genomic human to the amount of avian DNA and number of human /avian cells in BM. Drug response was tested by IV injection of therapeutic range doses of Imatinib (Glivec ®), Doxorubicin or dexamethasone, 48H after grafting cells. Drug levels were precalibrated to be non-toxic to the developing embryo by LD50 and BM cell viability compared to control (Taizi M et al Exp Hem 34:1698,2006, Grinberg I et al, Leuk Res. 33:1417, 2009). Six days later (E19) the embryos were sacrificed and the BM collected for FC and hematopoietic and non-hematopoietic tissues for molecular analysis. Results: The kinetics of leukemia cell engraftment in the BM on E15, E18, and E23 in BM and liver after cell injection on day E11 was assessed to determine the optimal treatment and readout times. The highest engraftment level in BM and liver was detected at E18 by Q-PCR, and FC in more than 90% of the injected embryos. We quantitatively compared the engraftment of AML cells at E18-20 without and with drug treatment that was administered IV 48 hours after cell injection. The average engraftment (±SD.) in the BM after one week was 4.5%+1.7 K562, 5.83% +0.88 LAMA-84, 11.2%+3.5 CHRF-4288, 8.9% +1.6 Raji (n=7-15 per group) and 2.5% fresh leukemia cells detected by FC and confirmed by Q-PCR. A single dose of either 0.75 mg Imatinib or 50 mg Doxorubicin /embryo previously calibrated to be non toxic to the embryos reduced engraftment of AML cells in BM and in several other organs by more than ten fold. A similar effect was also obtained by a single dose of 5mg dexamethasone in Raji injected embryos. Treatment with 0.5 mg Imatinib on injected ARH-77 (multiple myeloma) or Raji cells had no effect on cell engraftment, while treatment with a single non toxic dose of Revlimid as previously described eliminated engraftment of ARH77 cells (1), clearly demonstrating the specificity of the drugs and utility of the system. Conclusion: Our study demonstrates the potential utility of a practical and unique avian embryo model for testing drug activity on human AML cells in vivo. This system, under preclinical development, is expected to provide a new xenograft platform for real time affordable testing leukemia therapies. More importantly, this may open a new venue for individualized screening for response or resistance to specific therapeutic agents for the relapsed or refractive patient and may lead to better optimization of practical and applicable therapeutic strategies. Disclosures No relevant conflicts of interest to declare.

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Treatment-specific changes in gene expression discriminate in vivo drug response in human leukemia cells

Nature Genetics ◽

10.1038/ng1151 ◽

2003 ◽

Vol 34 (1) ◽

pp. 85-90 ◽

Cited By ~ 173

Author(s):

Meyling H. Cheok ◽

Wenjian Yang ◽

Ching-Hon Pui ◽

James R. Downing ◽

Cheng Cheng ◽

...

Keyword(s):

Gene Expression ◽

Drug Response ◽

Leukemia Cells ◽

Human Leukemia ◽

Human Leukemia Cells

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CD19-Redirected Cytotoxic T Cells Prevent Engraftment of Primary Human Leukemia Cells In Vivo.

Blood ◽

10.1182/blood.v114.22.3025.3025 ◽

2009 ◽

Vol 114 (22) ◽

pp. 3025-3025

Author(s):

Silke Landmeier ◽

Bianca Altvater ◽

Sibylle Pscherer ◽

Jutta Meltzer ◽

Josef Vormoor ◽

...

Keyword(s):

Bone Marrow ◽

T Cells ◽

T Cell ◽

High Risk ◽

B Cell ◽

Leukemia Cell ◽

Leukemic Cells ◽

Leukemia Cells ◽

Human Leukemia

Abstract Abstract 3025 Poster Board II-1001 Due to its restriction to the B-cell lineage and high surface expression in B-cell malignancies, CD19 is an attractive target antigen for immunological strategies in B-cell precursor acute lymphoblastic leukemia (BCP-ALL). While preclinical in vivo studies of CD19-specific cellular immunotherapy have generally used xenografts from human CD19+ leukemia cell lines, primary leukemia cells are likely to more closely mimic the disease in humans and allow to differentiate between standard and high risk situations. Therefore, we investigated the in vivo sensitivity of human leukemic bone marrow to adoptive immunotherapy with gene-modified CD19-specific T cells. Among 15 primary leukemias obtained from the bone marrow of pediatric patients at diagnosis, 10 were successfully engrafted in NOD/scid mice by intrafemoral injection within 6 to 20 weeks. For therapeutic experiments, we focused on one standard risk leukemia, characterized by a rapid and sustained response to multiagent chemotherapy, and on a leukemia bearing the high-risk feature of an MLL rearrangement, which was refractory to standard treatment. Titration experiments demonstrated reliable engraftment of 1×104 leukemic cells per mouse. For CD19-directed T-cell therapy, cytotoxic T cells (CTLs) with native specificity for Epstein-Barr virus antigens were expanded from 4 healthy donors and transduced to express either a codon-optimized CD19-specific chimeric antigen receptor (CAR) containing the intracellular signaling domain of the TCRz chain (CD19-z), or a control CAR directed against the neuroectodermal antigen GD2 (14.G2a-z). Costimulatory domains now commonly used to ensure sustained T-cell activation via CARs were not included, since previous studies have shown that CAR activity in virus-specific CTLs does not benefit from additional signaling elements. CTLs had a uniform CD8+ effector memory T-cell phenotype (CD45RO+, CCR7-), and CAR surface expression was 73±21%, range 32-93% (CD19-z, n=9) and 18±13%, range 6-35% (14.G2a-z, n=5). In vitro cytotoxicity experiments confirmed specific lysis of the CD19+ leukemia cell lines REH (51Cr release 59.7±7.2% at an effector target ratio of 20:1) and SupB15 (66.7±8.6) as well as primary CD19+ leukemic cells from 5 pediatric patients (47.2±13.2%), in the absence of background lysis by 14.G2a-z-transduced control CTLs. 1×104 leukemic cells per mouse from primary engrafted mice were transferred into further cohorts of NOD/scid mice by secondary intrafemoral transplantation, followed by adoptive transfer of 4 doses of 5×106 CTLs via tail vein injection on days 1, 4, 8, and 11. IL-2 (500 IU/mouse) was administered twice-weekly, and sequential murine bone marrow aspirates were analyzed for human leukemia engraftment by flow cytometry using human CD45 and CD19-specific antibodies starting 3 weeks after transplantation. CD19z CTLs prevented engraftment of the standard risk leukemia in 3 of 4 mice, while 3 of 4 control mice developed the leukemia (p = 0.158, Log Rank/Mantel-Cox Test). Moreover, while the MLL-rearranged human leukemia became detectable in the bone marrow of 4 of 5 control mice, followed by overt and fatal leukemia, 5 of 8 mice receiving transfusions of CD19-z transduced CTLs remained disease-free (p = 0.067), and 6 of 8 remained alive, one of them with detectable leukemia cells (p = 0.054) (see Figure). Thus, adoptive transfer of CD19-redirected CTLs efficiently delayed or prevented engraftment of both standard and high risk ALLs in mice and therefore provides a promising treatment option for patients with BCP-ALL refractory to standard treatment. Disclosures No relevant conflicts of interest to declare.

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Engraftment Capacity of Intratibialy Injected Multiple Myeloma Patient-Derived Bone Marrow-Cells In Vivo

Blood ◽

10.1182/blood.v116.21.3010.3010 ◽

2010 ◽

Vol 116 (21) ◽

pp. 3010-3010

Author(s):

Julia Schüler ◽

Dagmar Wider ◽

Kerstin Klingner ◽

Heinz-Herbert Fiebig ◽

Monika Engelhardt

Keyword(s):

Multiple Myeloma ◽

Bone Marrow ◽

Expression Pattern ◽

Peripheral Blood ◽

Bone Marrow Cells ◽

Nsg Mice ◽

Cell Engraftment ◽

Healthy Donors ◽

Marrow Cells

Abstract Abstract 3010 Introduction: In order to allow a better understanding of multiple myeloma (MM), the establishment of functional and reproducible in vivo models is widely pursued. Of available model systems, xenografts in immunodeficient mice reproduce the clinical situation advantageously. Here, the engraftment capacity of MM patient-derived bone marrow cells implanted into NOD/SCID-IL2-receptor-gamma-chain-/- (NSG) mice was meticulously investigated. Material and Methods: Bone marrow cells from 7 MM patients were injected intratibialy into NSG mice (n=5/patient). As controls, 5 mice received healthy donor bone marrow and 5 mice were mock-injected. Tumor growth was monitored via a) daily MM-symptom acquisition, such as hind limb paresis, apathy and consistent foot dragging, b) FACS (human HLA-A,B,C; CD138; CD45; CD38) and c) fluorescence-based in vivo imaging (FI, Kodak FX, Alexa750 labeled anti-human CD138, CD38, CD45 and HLA-ABC) in bone marrow, peripheral blood, spleen and lymph node sites of the respective animals. Results: There were significant differences in engraftment capacity, persistence of human cells and expression of selected markers between bone marrow of MM patients and healthy donors: 1.) infiltration of the spleen and lymph nodes was exclusively detected in NSG-mice bearing patient-derived MM cells, whereas cells of healthy donors were - if detected - exclusively found within the murine bone marrow; 2.) mean FI-areas in the bone marrow of MM-patient-derived injected mice were significantly increased as compared to mice bearing bone marrow cells of healthy donors (p=0.006); 3.) patient-derived MM cells expressed CD138, CD38 and HLA-ABC. In contrast, bone marrow cells of healthy donors expressed exclusively CD45 and CD138. The CD138 cell population determined by FACS in patients' bone marrow cells (before NSG-injection) decreased from a median of 11.3% to 0.8% 56 days after implantation (in NSG mice), either due to preferably CD138-negative plasma cell engraftment or the CD138 loss within the murine environment as previously described. Fifty-six days after implantation, patient-derived MM cells could be detected in all animals via FACS-analysis. Follow-up analyses by FI confirmed, that bone marrow engraftment was prominent and observed in all (35/35) NSG mice, albeit also in others organs. Patient-derived MM cells within the bone marrow could be detected in parallel via FACS- and FI-analyses in 10 NSG mice and within the peripheral blood in 12 NSG mice (total of 35 mice being examined). Maximal bone marrow-, peripheral blood- and spleen-engraftment numbers in NSG mice were as high as 4%, 25% and 52%, respectively, suggesting that in peripheral blood- and spleen-sites, MM-cell engraftment could even surmount that of bone marrow-sites. Spleen and other organ involvement observed in our xenografts have been confirmed in previous murine MM-models (Murillo et al. Clin Cancer Res, 2008), postulating that similarly to spleen-colony-forming-cells in hematopoiesis, spleen and other sites serve as fertile tumor engraftment locations.Differences in engraftment capacity and expression pattern between respective patient-derived MM specimen were evident, but did not strikingly correlate with MM-patients' characteristics, such as MM-subtypes, disease stage or expression pattern of the primary material; this observation also well correlating with previous reports (e.g. (Pilarski et al. Blood, 2000). Conclusions: Murine MM-models have shown to be exceedingly challenging in their ability to induce valid and trustworthy MM-patient-derived cell engraftment; here our NSG model suggest to harbor MM-cells. Our data demonstrates that intratibially-injected NSG mice mimic the clinical MM disease with respect to the disseminated nature of the disease and the indispensable engraftment of clonogenic plasma cells into the bone marrow. Collection of whole-body FI data proved to be a time- and animal-saving analysis that allows to closely monitor MM growth. Disclosures: No relevant conflicts of interest to declare.

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Erratum: Treatment-specific changes in gene expression discriminate in vivo drug response in human leukemia cells

Nature Genetics ◽

10.1038/ng0603-231b ◽

2003 ◽

Vol 34 (2) ◽

pp. 231-231

Author(s):

M H Cheok ◽

W Yang ◽

C-H Pui ◽

J R Downing ◽

C Cheng ◽

...

Keyword(s):

Gene Expression ◽

Drug Response ◽

Leukemia Cells ◽

Human Leukemia ◽

Human Leukemia Cells

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Genotoxic evaluation of ceftriaxone by in vivo micronucleus test in albino mice

International Journal of Basic & Clinical Pharmacology ◽

10.18203/2319-2003.ijbcp20183475 ◽

2018 ◽

Vol 7 (9) ◽

pp. 1705

Author(s):

Kunjumon Dayana ◽

Megaravalli R. Manasa

Keyword(s):

Bone Marrow ◽

Micronucleus Test ◽

Micronucleus Assay ◽

Generation Cephalosporin ◽

New Drugs ◽

Control Group ◽

Genotoxic Potential ◽

Polychromatic Erythrocytes ◽

Albino Mice

Background: Genotoxicity screening of drugs is essential. It is mandatory for new drugs. However, screening of drugs already in use is also necessary. Several cephalosporins are reported to induce chromosomal aberrations in previous studies. But there is paucity of data regarding the genotoxic potential of ceftriaxone. Hence the present study was undertaken to evaluate the genotoxic potential of ceftriaxone, a third generation cephalosporin, by micronucleus assay in albino mice.Methods: In vivo micronucleus test was performed with mice bone marrow after intraperitoneal injection of ceftriaxone at 100mg/kg BW and 200mg/kg BW at 24 hr and 48 hr harvest time. Mice bone marrow was harvested, and slides were prepared. The percentage of micronucleated polychromatic erythrocytes (% MnPCE) and the ratio of polychromatic erythrocytes to normochromatic erythrocytes (PCE:NCE) were determined. The data from ceftriaxone treated groups was compared with control group and analyzed using ANOVA followed by Dunnett's test.Results: Ceftriaxone at the dose of 100mg/kg BW and 200mg/kg BW did not exhibit any significant increase in the percentage of micronucleated polychromatic erythrocytes. It also did not decrease the ratio of polychromatic erythrocytes to normochromatic erythrocytes significantly.Conclusions: The present study demonstrates that ceftriaxone is not genotoxic in in vivo micronucleus study in albino mice at a dose of 100mg/kg BW and 200mg/kg BW.

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A novel BCMA/CD3 bispecific T-cell engager for the treatment of multiple myeloma induces selective lysis in vitro and in vivo

Leukemia ◽

10.1038/leu.2016.388 ◽

2016 ◽

Vol 31 (8) ◽

pp. 1743-1751 ◽

Cited By ~ 86

Author(s):

S Hipp ◽

Y-T Tai ◽

D Blanset ◽

P Deegen ◽

J Wahl ◽

...

Keyword(s):

Multiple Myeloma ◽

Bone Marrow ◽

T Cell ◽

Plasma Cells ◽

Ex Vivo ◽

Xenograft Model ◽

Selective Lysis ◽

Bispecific T Cell Engager

Abstract B-cell maturation antigen (BCMA) is a highly plasma cell-selective protein that is expressed on malignant plasma cells of multiple myeloma (MM) patients and therefore is an ideal target for T-cell redirecting therapies. We developed a bispecific T-cell engager (BiTE) targeting BCMA and CD3ɛ (BI 836909) and studied its therapeutic impacts on MM. BI 836909 induced selective lysis of BCMA-positive MM cells, activation of T cells, release of cytokines and T-cell proliferation; whereas BCMA-negative cells were not affected. Activity of BI 836909 was not influenced by the presence of bone marrow stromal cells, soluble BCMA or a proliferation-inducing ligand (APRIL). In ex vivo assays, BI 836909 induced potent autologous MM cell lysis in both, newly diagnosed and relapsed/refractory patient samples. In mouse xenograft studies, BI 836909 induced tumor cell depletion in a subcutaneous NCI-H929 xenograft model and prolonged survival in an orthotopic L-363 xenograft model. In a cynomolgus monkey study, administration of BI 836909 led to depletion of BCMA-positive plasma cells in the bone marrow. Taken together, these results show that BI 836909 is a highly potent and efficacious approach to selectively deplete BCMA-positive MM cells and represents a novel immunotherapeutic for the treatment of MM.

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