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Preclinical Efficacy of an Antibody‐Drug Conjugate Targeting TIM‐1 in Ovarian, Renal and Lung Tumor Models
Author(s) -
Gergel Lauren,
Forsberg Eric,
Pilsmaker Catherine,
Boyer James,
Round Sarah,
Borrelli Kathleen,
Sandland April,
Vargas Nohely,
Marsh Henry,
Keler Tibor,
Thomas Lawrence
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.945.15
Subject(s) - antibody , cancer research , monoclonal antibody , muc1 , in vivo , medicine , antibody drug conjugate , immunology , biology , antigen , microbiology and biotechnology
T cell immunoglobulin and mucin domain 1 (TIM‐1) is a type I transmembrane glycoprotein, also described as kidney injury molecule 1 (KIM‐1) and as hepatitis A virus cellular receptor 1 (HAVCR1). TIM‐1 has been shown to have upregulated expression in several human cancers, but has restricted expression in healthy tissues, thus it represents a promising target for antibody mediated therapy. To this end we have developed a fully human monoclonal antibody specific for the extracellular domain of TIM‐1, covalently linked to the potent cytotoxin monomethyl auristatin E (MMAE). We have designated this antibody‐drug conjugate as CDX‐014. Three TIM‐1 expressing xenograft models (Caki‐1, a renal clear cell carcinoma; IGROV‐1, an ovarian adenocarcinoma, and A549, a lung carcinoma) have been established to demonstrate the efficacy of CDX‐014 in vivo against human tumors. In all models, cells were grown in culture and then implanted subcutaneously into immunocompromised mice. When tumors reached an average of approximately 0.3cm 3 , mice were split into equivalently sized control and treatment groups. Dose dependent efficacy of CDX‐014 was shown in all models by a decreased rate of tumor growth and extended group survival. These studies support the further development of CDX‐014, including manufacturing activities and IND‐enabling studies, in order to advance towards clinical studies in clear cell carcinomas and potentially other TIM‐1 expressing tumors.