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We previously demonstrated the feasibility of generating therapeutic numbers of cytotoxic T lymphocyte (CTL) clones expressing a CD20-specific scFvFc:CD3zeta chimeric T cell receptor (cTCR), making them specifically cytotoxic for CD20+ B lymphoma cells. However, the process of generating and expanding he CTL clones was laborious, the CTL clones expressed(More)
Despite the promise of radioimmunotherapy using anti-CD20 antibodies (Ab) for the treatment of relapsed patients with indolent non-Hodgkin lymphoma (NHL), most patients treated with conventional doses of (131)I-tositumomab or (90)Y-ibritumomab eventually relapse. We did comparative assessments using conventional radioimmunotherapy targeting CD20, CD22, and(More)
The meiotic recombination gene rec10, which encodes a region-specific activator of recombination in Schizosaccharomyces pombe, has been cloned by genetic complementation and its nucleotide sequence determined. The rec10 gene was identified in a 5.6-kb cloned fragment by partial-deletion and insertion experiments. The nucleotide sequence of 3.5 kb of this(More)
Cellular immune responses have the potential to elicit dramatic and sustained clinical remissions in lymphoma patients. Recent clinical trial data demonstrate that modification of T cells with chimeric antigen receptors (CARs) is a promising strategy. T cells containing CARs with costimulatory domains exhibit improved activity against tumors. We conducted a(More)
We have targeted CD22 as a novel tumor-associated Ag for recognition by human CTL genetically modified to express chimeric TCR (cTCR) recognizing this surface molecule. CD22-specific cTCR targeting different epitopes of the CD22 molecule promoted efficient lysis of target cells expressing high levels of CD22 with a maximum lytic potential that appeared to(More)
We have earlier shown that attenuated measles virus (MV) has therapeutic potential as a replicating oncolytic virus in models of non-Hodgkin's lymphoma (NHL). In the current study, we investigated whether we could obtain replicating MVs capable of entering CD20(+) target cells through an interaction between a single-chain (scFv) anti-CD20 antibody and the(More)
Acute myelogenous leukemia (AML) currently kills the majority of afflicted patients despite combination chemotherapy and hematopoietic cell transplantation (HCT). Our group has documented the promise of radiolabeled anti-CD45 monoclonal antibodies (Ab) administered in the setting of allogeneic HCT for AML, but toxicity remains high, and cure rates are only(More)
Radioimmunotherapy (RIT) with α-emitting radionuclides is an attractive approach for the treatment of minimal residual disease because the short path lengths and high energies of α-particles produce optimal cytotoxicity at small target sites while minimizing damage to surrounding normal tissues. Pretargeted RIT (PRIT) using antibody-streptavidin (Ab-SA)(More)
We investigated relationships among chimeric TCR (cTCR) expression density, target Ag density, and cTCR triggering to predict lysis of target cells by cTCR(+) CD8(+) T human cells as a function of Ag density. Triggering of cTCR and canonical TCR by Ag could be quantified by the same mathematical equation, but cTCR represented a special case in which serial(More)
We describe the use of pretargeted radioimmunotherapy (PRIT) using an anti-murine CD45 antibody-streptavidin (SA) conjugate followed by radiobiotin to deliver radiation selectively to murine hematolymphoid tissues, which may potentially augment the efficacy and decrease the toxicity of radioimmunotherapy for disseminated murine leukemia. Biodistribution and(More)