Dataset Information

Maytansinoid immunoconjugate IMGN901 is cytotoxic in a three-dimensional culture model of multiple myeloma.

ABSTRACT: Environmental-mediated drug-resistance (EM-DR) presents a major challenge for therapeutic development. Tissue microenvironment in the form of extracellular matrix, soluble factors, and stroma contribute to EM-DR. In multiple myeloma (MM), drug-resistance has hindered treatment success with 5-year survival rates remaining <50%. Here we evaluated IMGN901, a maytansinoid immunoconjugate, for its ability to overcome EM-DR alone or in combination with lenalidomide or dexamethasone. We show that while adhesion of MM cells to the extracellular matrix reduces potency of IMGN901, it remains cytotoxic with an average LC50=43 nM. However, only a combination of IMGN901, lenalidomide, and dexamethasone was able to overcome drug-resistance arising from the direct contact between MM and stromal cells. We demonstrate that multi-drug resistance protein-1 (MDR-1) was upregulated in MM cells grown in contact with stroma, likely responsible for the observed resistance. This study emphasizes the importance of incorporating the elements of tumor microenvironment during preclinical testing of novel therapeutics.

SUBMITTER: Nierste BA

PROVIDER: S-EPMC4913235 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Maytansinoid immunoconjugate IMGN901 is cytotoxic in a three-dimensional culture model of multiple myeloma.

Nierste Brittany A BA Gunn Ellen J EJ Whiteman Kathleen R KR Lutz Robert J RJ Kirshner Julia J

American journal of blood research 20160518 1

Environmental-mediated drug-resistance (EM-DR) presents a major challenge for therapeutic development. Tissue microenvironment in the form of extracellular matrix, soluble factors, and stroma contribute to EM-DR. In multiple myeloma (MM), drug-resistance has hindered treatment success with 5-year survival rates remaining <50%. Here we evaluated IMGN901, a maytansinoid immunoconjugate, for its ability to overcome EM-DR alone or in combination with lenalidomide or dexamethasone. We show that while ...[more]

PMID: 27335686

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Dataset Information

Maytansinoid immunoconjugate IMGN901 is cytotoxic in a three-dimensional culture model of multiple myeloma.

Publications

Maytansinoid immunoconjugate IMGN901 is cytotoxic in a three-dimensional culture model of multiple myeloma.

Similar Datasets

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