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Combination Therapy of an Antibody Specific for Transferrin Receptor 1 (ch128.1/IgG1) With Bortezomib or Lenalidomide Results in Increased Survival in an In Vivo Model of Human Multiple Myeloma: A Brief Communication
被引:0
|作者:
Candelaria, Pierre V.
[1
]
Nava, Miguel
[1
]
Martinez-Maza, Otoniel
[2
,4
,5
,6
]
Daniels-Wells, Tracy R.
[1
]
Penichet, Manuel L.
[1
,3
,4
,6
,7
]
机构:
[1] Univ Calif Los Angeles, David Geffen Sch Med, Div Surg Oncol, Dept Surg, 10833 Le Conte Ave CHS 54-140,Box 951782, Los Angeles, CA 90095 USA
[2] Univ Calif Los Angeles, David Geffen Sch Med, Dept Obstet & Gynecol, Los Angeles, CA 90095 USA
[3] Univ Calif Los Angeles, David Geffen Sch Med, Dept Microbiol Immunol & Mol Genet, Los Angeles, CA 90095 USA
[4] Univ Calif Los Angeles, AIDS Inst, Los Angeles, CA USA
[5] Univ Calif Los Angeles, Dept Epidemiol, UCLA Fielding Sch Publ Hlth, Los Angeles, CA USA
[6] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90024 USA
[7] Univ Calif Los Angeles, Inst Mol Biol, Los Angeles, CA 90024 USA
基金:
美国国家卫生研究院;
关键词:
combination therapy;
multiple myeloma;
bortezomib;
lenalidomide;
anti-TfR1;
antibody;
BEIGE MUTATION;
CELLS;
MOUSE;
RESISTANCE;
EXPRESSION;
INHIBITOR;
MECHANISM;
D O I:
10.1097/CJI.0000000000000419
中图分类号:
R73 [肿瘤学];
学科分类号:
100214 ;
摘要:
Transferrin receptor 1 (TfR1) is a universal cancer marker and a meaningful target for antibody-based immunotherapy. We previously developed a mouse/human chimeric antibody (ch128.1/IgG1) specific for the human TfR1 and reported that treatment of SCID-Beige mice bearing disseminated human multiple myeloma (MM) cells with ch128.1/IgG1 results in significant antitumor activity in early-stage and late-stage disease. Both bortezomib and lenalidomide are Food and Drug Administration (FDA) approved therapeutics used to treat MM in combination with other agents. Since combining treatments with different mechanisms of action is an effective antitumor strategy and given the relevance of bortezomib and lenalidomide in MM therapy, we decided to explore, for the first time, the combination of bortezomib or lenalidomide treatment with ch128.1/IgG1 within the context of late-stage MM disease. We found that treatment with a single dose of ch128.1/IgG1, or multiple doses of bortezomib or lenalidomide, used as single agents, results in significant antitumor activity in SCID-Beige mice bearing late-stage disseminated human MM.1S tumors. However, this antitumor activity is superior when ch128.1/IgG1 is combined with either bortezomib or lenalidomide, showing significantly longer survival compared with any therapy used alone. These novel results suggest that the combinations of ch128.1/IgG1 and bortezomib or lenalidomide are promising strategies against MM.
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页码:227 / 230
页数:4
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