Abstract
PurposeTriple-negative breast cancer (TNBC) is related with a poor prognosis as patients do hardly benefit from approved therapies. CD138 (Syndecan-1) is upregulated on human breast cancers. Indatuximab ravtansine (BT062) is an antibody-drug-conjugate that specifically targets CD138-expressing cells and has previously shown clinical activity in multiple myeloma. Here we show indatuximab ravtansine as a potential mono- and combination therapy for TNBC.MethodsThe effects of indatuximab ravtansine were assessed in vitro in SK-BR-3 and T47D breast cancer cell lines. The in vivo effects of indatuximab ravtansine alone and in combination with docetaxel or paclitaxel were assessed in MAXF401, MAXF1384 and MAXF1322 xenograft TNBC models.ResultsCD138+ SK-BR-3 and T47D cells were highly sensitive to indatuximab ravtansine. The high CD138-expressing MAXF401 xenograft model demonstrated strong inhibition of tumor growth with 4 mg/kg indatuximab ravtansine. High doses of indatuximab ravtansine (8 mg/kg), docetaxel and the combination of both led to complete remission. In the low CD138-expressing MAXF1384 xenograft model, only combination of indatuximab ravtansine and docetaxel demonstrated a significant efficacy. In the MAXF1322 xenograft model, indatuximab ravtansine alone and in combination with paclitaxel elicited complete remission.ConclusionsThese data demonstrate potential use of indatuximab ravtansine in combination with docetaxel or paclitaxel for CD138-positive TNBC.
Highlights
Breast cancer represents the most common non-dermatological malignant neoplasm in women and, after lung cancer, it is the second leading cause of cancer-related death among women
The lack of targeted therapies and the poor prognosis of Triple-negative breast cancer (TNBC) means that clinical research in the area of TNBC is of great importance [4]
The binding of nBT062 and resulting characterization of CD138 expression indicated variable expression of CD138 between the two cell lines tested; notably, expression was 2fold higher in the SK-BR-3 cell line compared with the T47D line (Table VI)
Summary
Breast cancer represents the most common non-dermatological malignant neoplasm in women and, after lung cancer, it is the second leading cause of cancer-related death among women. In 2016, approximately 40,000 women in the United States died from breast cancer [1], and 92,300 were predicted to die from the disease in Europe [2]. Triple-negative breast cancer (TNBC), in which the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) are not expressed [3, 4], accounts for approximately 118 Page 2 of 10. The lack of target receptors (ER, PR, and HER2) means that patients with TNBC do not benefit from hormonal or anti-HER2-based therapy [4]. Chemotherapy represents the mainstay of systemic treatment, patients with advanced disease typically respond poorly and rapidly progress [3]. The lack of targeted therapies and the poor prognosis of TNBC means that clinical research in the area of TNBC is of great importance [4]
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