Naptumomab estafenatox: targeted immunotherapy with a novel immunotoxin.
AffiliationCambridge University Health Partners, Addenbrooke's Hospital, Cambridge, UK, firstname.lastname@example.org.
MetadataShow full item record
AbstractImprovement of cancer therapy by introducing new concepts is still urgent even though there have been major advancements lately. Immunotherapy is well on the way to becoming an established tool in the cancer treatment armory. It seems that a combination of (1) activation of immune effector cells and selective targeting of them to tumors and (2) the inhibition of immune suppression often induced by the tumor itself are necessary to achieve the therapeutic goal. The immunotoxin naptumomab estafenatox was developed in an effort to activate and target the patient's own T cells to their tumor, by fusing a superantigen (SAg) variant that activates T lymphocytes to the Fab moiety of a tumor-reactive monoclonal antibody. Naptumomab estafenatox targets the 5T4 tumor antigen, a 72-kDa oncofetal trophoblast protein expressed on many carcinomas, including renal cell carcinoma. The therapeutic effect is associated with activation of SAg-binding T cells. The SAg-binding T lymphocytes expand, differentiate to effector cells, and infiltrate the tumor. The therapeutic efficacy is most likely related to the dual mechanism of tumor cell killing: (1) direct lysis by cytotoxic T lymphocytes of tumor cells expressing the antigen recognized by the antibody moiety of the fusion protein and (2) secretion of cytokines eliminating antigen-negative tumor cell variants. Naptumomab estafenatox has been clinically tested in a range of solid tumors with focus on renal cell carcinoma. This review looks at the clinical experience with the new immunotoxin and its potential.
CitationNaptumomab estafenatox: targeted immunotherapy with a novel immunotoxin. 2014, 16 (2):370 Curr Oncol Rep
JournalCurrent Oncology Reports
- Naptumomab estafenatox: a new immunoconjugate.
- Authors: Robinson MK, Alpaugh RK, Borghaei H
- Issue date: 2010 Feb
- Naptumomab estafenatox, an engineered antibody-superantigen fusion protein with low toxicity and reduced antigenicity.
- Authors: Forsberg G, Skartved NJ, Wallén-Ohman M, Nyhlén HC, Behm K, Hedlund G, Nederman T
- Issue date: 2010 Jun
- The tumor targeted superantigen ABR-217620 selectively engages TRBV7-9 and exploits TCR-pMHC affinity mimicry in mediating T cell cytotoxicity.
- Authors: Hedlund G, Eriksson H, Sundstedt A, Forsberg G, Jakobsen BK, Pumphrey N, Rödström K, Lindkvist-Petersson K, Björk P
- Issue date: 2013
- Immunological response and overall survival in a subset of advanced renal cell carcinoma patients from a randomized phase 2/3 study of naptumomab estafenatox plus IFN-α versus IFN-α.
- Authors: Elkord E, Burt DJ, Sundstedt A, Nordle Ö, Hedlund G, Hawkins RE
- Issue date: 2015 Feb 28
- Phage-selected primate antibodies fused to superantigens for immunotherapy of malignant melanoma.
- Authors: Tordsson JM, Ohlsson LG, Abrahmsén LB, Karlström PJ, Lando PA, Brodin TN
- Issue date: 2000 Mar