99Tcm-LL1

Juweid, Malik E.; Rm, Dunn; Rm, Sharkey; Ad, Rubin; Hj, Hansen; Dm, Goldenberg

doi:10.1097/00006231-199702000-00009

Cited by 4 publications

(1 citation statement)

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“…Thus, a pilot clinical imaging study was conducted previously to evaluate the imaging/targeting potential of a 99m Tc-labeled FabЈ fragment of LL1. In the 6 patients with various malignancies, including 1 patient with multiple myeloma and 2 with NHL, this mAb was shown to be safe and to provide rapid, effective targeting of the bone marrow and spleen (28). In addition, cell surface CD74 expression can be up-regulated on various cancer cell lines using IFN-␥ (6), a clinically available cytokine, thereby providing an opportunity to additionally enhance tumor cell targeting with the LL1 mAb.…”

Section: Discussionmentioning

confidence: 99%

CD74 Is Expressed by Multiple Myeloma and Is a Promising Target for Therapy

Burton

Ely

Reddy

et al. 2004

Clinical Cancer Research

144

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Purpose: CD74 (HLA-DR-associated invariant chain) plays a role in antigen presentation. In addition to its expression on antigen-presenting cells, it is expressed by carcinomas of renal, lung, gastric, and thymic origin and by certain sarcomas. The restricted expression of CD74 by normal tissues and its very rapid internalization make CD74 an attractive therapeutic target for both cancer and immunologic diseases. Preclinical efficacy of anti-CD74 monoclonal antibody (mAb) therapy has been demonstrated in B-lymphoma models. Because there are few validated antigenic targets in multiple myeloma, CD74 expression was examined.Experimental Design: CD74 expression was assessed by immunohistochemistry in bone marrow biopsies of known multiple myeloma cases. Its expression was measured by flow cytometry in multiple myeloma lines, and CD74 mRNA expression was determined by reverse transcription-PCR. In addition, the in vitro antiproliferative effect of LL1 mAb was evaluated on a CD74؉ multiple myeloma cell line using a [ 3 H]thymidine incorporation assay.Results: CD74 expression was observed in 19 of 22 cases of multiple myeloma, with most expressing moderate to high levels in the majority of malignant plasma cells. CD74 was expressed by most multiple myeloma cell lines, as was CD74 mRNA, at levels mirroring CD74 protein. Also, unlabeled LL1 mAb mediated in vitro growth inhibition of a CD74؉ multiple myeloma cell line.Conclusions: CD74 expression is frequent in multiple myeloma, with predominant expression by the malignant plasma cells. Because anti-CD74 mAbs internalize very rapidly and LL1 mAb has shown efficacy in B-lymphoma models, CD74 represents a novel and promising target for treatment of multiple myeloma. Therefore, LL1 mAb is well suited as a carrier of radionuclides, drugs, or toxins, and also has activity as an unlabeled mAb, thereby supporting its development for this unmet need in cancer therapy.

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Section: Discussionmentioning

confidence: 99%