177Lu-antibody conjugates for single-cell kill of B-lymphoma cells in vitro and for therapy of micrometastases in vivo

Michel, Rosana B.; Andrews, Philip M.; Rosario, Adriane V.; Goldenberg, David M.; Mattes, M. Jules

doi:10.1016/j.nucmedbio.2005.01.003

Cited by 35 publications

(17 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These results are in line with experimental data by Michel et al, who showed that the rate of eradication of single cells and micrometastases was higher with 177 Lu than with 90 Y (29). By contrast, 1 study assessed anti-CD20 pretargeted radioimmunotherapy on lymphoma xenografts and found a higher efficacy with 90 Y (30).…”

Section: Discussionsupporting

confidence: 88%

See 1 more Smart Citation

Dose Deposits from ⁹⁰Y, ¹⁷⁷Lu, ¹¹¹In, and ¹⁶¹Tb in Micrometastases of Various Sizes: Implications for Radiopharmaceutical Therapy

et al. 2016

View full text Add to dashboard Cite

show abstract

Section: Discussionsupporting

confidence: 88%

“…Studies have shown that the rate of eradication of micrometastases and single cells is higher with 111 In than with either 90 Y (16) or 177 Lu (29). By consequence, many teams actively work on developing 111 In-labeled radiopharmaceuticals aimed at targeting micrometastases or cancer stem cells (17,18).…”

Section: Discussionmentioning

confidence: 99%

Dose Deposits from ⁹⁰Y, ¹⁷⁷Lu, ¹¹¹In, and ¹⁶¹Tb in Micrometastases of Various Sizes: Implications for Radiopharmaceutical Therapy

et al. 2016

View full text Add to dashboard Cite

show abstract

“…This was corroborated in a recent study of 177 Lu-LL1 (50). The potency of LL1 labeled with Auger electron-emitting radioisotopes is due to the remarkably high level of accumulation within cells.…”

supporting

confidence: 73%

CD74: A New Candidate Target for the Immunotherapy of B-Cell Neoplasms

Stein

Mattes

Cardillo

et al. 2007

Clinical Cancer Research

Self Cite

197

164

View full text Add to dashboard Cite

CD74 is an integral membrane protein that functions as a MHC class II chaperone. Moreover, it has recently been shown to have a role as an accessory-signaling molecule and has been implicated in malignant B-cell proliferation and survival.These biological functions combined with expression of CD74 on malignant B cells and limited expression on normal tissues implicate CD74 as a potential therapeutic target. The anti-CD74 monoclonal antibody LL1 has been humanized (hLL1milatuzumab or IMMU-115) and can provide the basis for novel therapeutic approaches to B-cell malignancies, particularly because this antibody shows rapid internalization into CD74 + malignant cells. This article reviews the preclinical evaluations of LL1, its humanized form, and isotope, drug, and toxin conjugates. These studies show that unconjugated hLL1and conjugates of hLL1constructs with radioisotopes, doxorubicin, and frog RNase have high antitumor activity innon^Hodgkin's lymphoma and multiple myeloma invitro andin tumor xenograft models. Singledose studies of hLL1 in monkeys showed no adverse effects but did decrease circulating B and T lymphocytes and natural killer cells. When evaluated in combination with rituximab, either equivalent or improved efficacy, compared with either antibody alone, was observed. CD74 is a new candidate target for the immunotherapy of neoplasms expressing this antigen, which can be exploited using either a naked antibody or conjugated to isotopes, drugs, or toxins. CD74 (invariant chain, Ii) is a type II transmembraneglycoprotein that associates with the MHC class II a and h chains and directs the transport of the ahIi (invariant chain) complexes to endosomes and lysosomes (1 -4). In addition, CD74 is involved in signaling pathway functioning as a survival receptor (5). These biological functions, combined with expression of CD74 on malignant B cells and limited expression on normal tissues, implicate CD74 as a potential therapeutic target. The anti-CD74 monoclonal antibody (mAb) LL1 has been humanized (hLL1 milatuzumab or IMMU-115) and can provide the basis for novel therapeutic approaches to B-cell malignancies. This article reviews the preclinical evaluations of LL1, its humanized form, and isotope, drug, and toxin conjugates. The evidence suggests that hLL1 is a promising candidate antibody for the therapy of CD74-expressing malignancies, such as non -Hodgkin's lymphoma (NHL) and multiple myeloma (MM). Due to its rapid internalization property, hLL1 also shows considerable promise as a drug, isotope, or toxin immunoconjugate. CD74 Molecule: Structure, Function, and ExpressionCD74 has 30 NH 2 -terminal, intracytoplasmic amino acid residues, a 26-amino acid hydrophobic transmembrane region, and a 160-amino acid extracytoplasmic domain containing two N-linked carbohydrate chains (1, 6). Once synthesized, CD74, DRa, and DRh begin to associate within the endoplasmic reticulum. This is believed to occur by sequential addition of DRa/h heterodimers to a trimeric core of CD74 molecules until a nine-subunit...

show abstract

“…4 and 5), and, probably as a consequence, did not display any specific cytotoxicity. Whereas it can be argued that 131 I does not provide a fair comparison, because it is a nonresidualizing label, similar results have been obtained with residualizing h-particle emitters, such as 90 Y or 177 Lu (1,3,4,6,8). Nonspecific cytotoxicity from 90 Y (1) and 177 Lu (8) is similar to that from 131 I, and an increase in the retention of antibody catabolites, with anti -HER-2 antibodies, is not of sufficient magnitude to have a major impact.…”

Section: Discussionmentioning

confidence: 70%

In vitrocytotoxicity of carcinoma cells with 111In-labeled antibodies to HER-2

Michel

Andrews²,

Castillo³

et al. 2005

Molecular Cancer Therapeutics

Self Cite

View full text Add to dashboard Cite

show abstract

177Lu-antibody conjugates for single-cell kill of B-lymphoma cells in vitro and for therapy of micrometastases in vivo

Cited by 35 publications

References 14 publications

Dose Deposits from ⁹⁰Y, ¹⁷⁷Lu, ¹¹¹In, and ¹⁶¹Tb in Micrometastases of Various Sizes: Implications for Radiopharmaceutical Therapy

Dose Deposits from ⁹⁰Y, ¹⁷⁷Lu, ¹¹¹In, and ¹⁶¹Tb in Micrometastases of Various Sizes: Implications for Radiopharmaceutical Therapy

CD74: A New Candidate Target for the Immunotherapy of B-Cell Neoplasms

In vitrocytotoxicity of carcinoma cells with 111In-labeled antibodies to HER-2

Contact Info

Product

Resources

About

177Lu-antibody conjugates for single-cell kill of B-lymphoma cells in vitro and for therapy of micrometastases in vivo

Cited by 35 publications

References 14 publications

Dose Deposits from 90Y, 177Lu, 111In, and 161Tb in Micrometastases of Various Sizes: Implications for Radiopharmaceutical Therapy

Dose Deposits from 90Y, 177Lu, 111In, and 161Tb in Micrometastases of Various Sizes: Implications for Radiopharmaceutical Therapy

CD74: A New Candidate Target for the Immunotherapy of B-Cell Neoplasms

In vitrocytotoxicity of carcinoma cells with 111In-labeled antibodies to HER-2

Contact Info

Product

Resources

About

Dose Deposits from ⁹⁰Y, ¹⁷⁷Lu, ¹¹¹In, and ¹⁶¹Tb in Micrometastases of Various Sizes: Implications for Radiopharmaceutical Therapy

Dose Deposits from ⁹⁰Y, ¹⁷⁷Lu, ¹¹¹In, and ¹⁶¹Tb in Micrometastases of Various Sizes: Implications for Radiopharmaceutical Therapy