Removal of Marrow T Cells With Okt3-Okt11 Monoclonal Antibodies and Complement to Prevent Acute Graft-Versus-Host Disease

Hervé, P.; Flesch, M.; Jy, Cahn; Racadot, E; Plouvier, E; Lamy, B.; Rozenbaum, A; Noir, A; Rl, Des Floris; Peters, Antoine H.F.M.

doi:10.1097/00007890-198502000-00006

Cited by 40 publications

(8 citation statements)

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“…Removal of T lymphocytes from the graft is a reliable method for preventing GVHD, and a number of negative selection techniques for T-cell depletion have been described and evaluated in clinical trials. 17,18,[34][35][36][37][38][39][40][41][42][43] However, most of these techniques cannot deplete T cells sufficiently to eliminate the need for posttransplantation pharmacologic immunosuppression. In addition, transplantation with T-cell-depleted grafts is associated with a higher incidence of posttransplantation EBV-associated lymphoproliferative syndrome [44][45][46][47] and a high incidence of nonengraftment or rejection.…”

Section: Discussionmentioning

confidence: 99%

Transplantation of highly purified CD34+ progenitor cells from unrelated donors in pediatric leukemia

Lang

Handgretinger

Niethammer

et al. 2003

Blood

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Unrelated donors are commonly used for hematopoietic stem cell transplants, but graft-versus-host disease (GVHD) is a major problem. We investigated whether transplantation of purified mobilized peripheral-blood CD34 ؉ stem cells from unrelated donors would prevent acute and chronic GVHD in pediatric patients with leukemia and avert the need for pharmacologic immunosuppression. Thirty-one pediatric patients with acute lymphoblastic leukemia (ALL, n ‫؍‬ 16), acute myeloid (n ‫؍‬ 7), chronic myeloid (n ‫؍‬ 6), or juvenile myelomonocytic leukemia (n ‫؍‬ 2) underwent transplantation. The median purity of CD34 ؉ cells after positive magnetactivated cell sorting was 98.5%. Patients received a median of 8.0 ؋ 10 6 CD34 ؉ cells and 6 ؋ 10 3 CD3 ؉ T lymphocytes per kilogram, with no posttransplantation pharmacologic immunosuppression. Primary acute GVHD > grade II was seen in only 10% of patients (n ‫؍‬ 3) and occurred only after human herpesvirus 6 (HHV 6) infection. Two patients had limited chronic GVHD. Engraftment occurred in all patients (primary engraftment, n ‫؍‬ 26; engraftment after reconditioning, n ‫؍‬ 5). The 2-year survival estimate was 38% for all patients and 63% for patients with ALL in complete remission. Patients with myeloid malignancies had a poor outcome.In comparison to a historical control group who received unmanipulated bone marrow, our patients had a lower incidence of GVHD (P < .001). No difference was observed in the probability of relapse or survival. Study patients with ALL in remission showed a trend toward better survival (P ‫؍‬ .07). Transplantation of purified peripheral-blood CD34 ؉ cells from unrelated donors effectively minimizes GVHD and may be a good therapeutic option for patients with relapsed ALL. (Blood. 2003;

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Section: Discussionmentioning

confidence: 99%

Transplantation of highly purified CD34+ progenitor cells from unrelated donors in pediatric leukemia

Lang

Handgretinger

Niethammer

et al. 2003

Blood

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“…Negative selection can be achieved either through physical methods such as counterflow elutriation [3,4,5] or soybean lectin agglutination (SBA) and sheep red blood cell (sRBC)-rosette depletion (E-rosetting) [6,7,8,9,10], or immunological methods using monoclonal antibodies [5,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29]. Monoclonal antibodies can be used with or without complement, or conjugated to toxins.…”

Section: T-cell Depletion Techniquesmentioning

confidence: 99%

Effects of T-Cell Depletion on Allogeneic Hematopoietic Stem Cell Transplantation Outcomes in AML Patients

Hobbs

Perales

2015

JCM

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Graft versus host disease (GVHD) remains one of the leading causes of morbidity and mortality associated with conventional allogeneic hematopoietic stem cell transplantation (HCT). The use of T-cell depletion significantly reduces this complication. Recent prospective and retrospective data suggest that, in patients with AML in first complete remission, CD34+ selected grafts afford overall and relapse-free survival comparable to those observed in recipients of conventional grafts, while significantly decreasing GVHD. In addition, CD34+ selected grafts allow older patients, and those with medical comorbidities or with only HLA-mismatched donors to successfully undergo transplantation. Prospective data are needed to further define which groups of patients with AML are most likely to benefit from CD34+ selected grafts. Here we review the history of T-cell depletion in AML, and techniques used. We then summarize the contemporary literature using CD34+ selection in recipients of matched or partially mismatched donors (7/8 or 8/8 HLA-matched), and provide a summary of the risks and benefits of using T-cell depletion.

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“…First, there is no need to reengineer the bispecific BiTE, and if an intact anti-tumor IgG is FDA approved, one may obtain it from the pharmacy. Similarly, a murine anti-human CD3 antibody is commercially available and clinically tested [14]. Second, once combined into a bispecific format, their combined molecular weights (300 kda) would preclude blood clearance by the kidney.…”

Section: Discussionmentioning

confidence: 99%

Generation of dual specific bivalent BiTEs (dbBIspecific T-cell Engaging antibodies) for cellular immunotherapy

Kujawski

Bhatacharya

et al. 2019

Preprint

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Bispecific T-cell engaging antibodies (BiTES), comprising dual anti-CD3 and anti-tumor antigen scFv fragments, are important therapeutic agents for the treatment of cancer. The dual scFv construct for BiTES requires proper protein folding while their small molecular size leads to rapid kidney clearance. Here we show that an intact (150 kDa) anti-tumor antigen antibody to CEA was joined in high yield (ca. 30%) to intact (150 kDa) anti-murine and anti-human CD3 antibodies using hinge region specific Click chemistry to form dual-specific, bivalent BiTES (db BiTES, 300 kDa). The interlocked hinge regions are compatible with a structural model that fits the electron micrographs of the 300 kDa particles. Compared to intact anti-CEA antibody, dbBiTES maintain high in vivo tumor targeting as demonstrated by PET imaging, and redirect dbBiTE coated T-cells (1 microgram/10 million cells) to kill CEA + target cells both in vitro, and in vivo in CEA transgenic mice.

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Removal of Marrow T Cells With Okt3-Okt11 Monoclonal Antibodies and Complement to Prevent Acute Graft-Versus-Host Disease

Cited by 40 publications

References 1 publication

Transplantation of highly purified CD34+ progenitor cells from unrelated donors in pediatric leukemia

Transplantation of highly purified CD34+ progenitor cells from unrelated donors in pediatric leukemia

Effects of T-Cell Depletion on Allogeneic Hematopoietic Stem Cell Transplantation Outcomes in AML Patients

Generation of dual specific bivalent BiTEs (dbBIspecific T-cell Engaging antibodies) for cellular immunotherapy

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