PMID: 9537591Apr 16, 1998Paper

Repeated treatment with antibody-targeted superantigens strongly inhibits tumor growth

International Journal of Cancer. Journal International Du Cancer
A RosendahlM Dohlsten

Abstract

Superantigens (SAg) are microbial proteins with the capacity to activate a large proportion of T cells. We have developed a novel approach for cancer immunotherapy by genetically fusing the SAg staphylococcal enterotoxin A (SEA) to a Fab-fragment of a tumor-specific antibody. Repeated exposure to SEA induces a state of unresponsiveness including cell deletion and functional hyporesponsiveness, i.e., anergy. In this study we have developed improved therapeutic schedules to allow repeated injections of Fab-SEA, limit development of immunological unresponsiveness and promote maximal anti-tumor response. Four daily injections of Fab-SEA to mice carrying B 16-C215 lung metastases resulted in 90-95% reduction in the number of metastases. However, the animals did retain a minimal residual tumor disease. The immune system was in a hyporesponsive state after 4 daily Fab-SEA injections, and further injections did not improve therapy. Two repeated cycles, each comprising 4 daily injections of Fab-SEA, significantly prolonged the survival and resulted in complete cure of a fraction of the animals. A rest period of 10 days between the cycles was required to mount an efficient secondary anti-tumor response. This secondary immune response was...Continue Reading

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Citations

Sep 8, 1999·The Journal of Experimental Medicine·T NishimuraA Ohta
Jul 29, 2009·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Hossein BorghaeiRoger B Cohen
Jan 8, 2010·Expert Opinion on Biological Therapy·Matthew K RobinsonHossein Borghaei
Nov 4, 2004·The Journal of Surgical Research·Elizabeth J McConnellHeidi Nelson
Jul 9, 2004·Biochimica Et Biophysica Acta·Said DermimePeter L Stern
Feb 18, 2004·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Jonathan D ChengAndré Rogatko
Mar 17, 1999·International Journal of Cancer. Journal International Du Cancer·A RosendahlM Dohlsten

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