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[Cancer Research 59, 2536-2540, June 1, 1999]
© 1999 American Association for Cancer Research
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[Cancer Research 59, 2536-2540, June 1, 1999]
© 1999 American Association for Cancer Research

Advances in Brief

Recombinant Virus Vaccination against "Self" Antigens UsingAnchor-fixed Immunogens

Kari R. Irvine, Maria R. Parkhurst, Eliza P. Shulman, Janis P. Tupesis, Mary Custer, Christopher E. Touloukian, Paul F. Robbins, Alicia Gómez Yafal, Patricia Greenhalgh, Roger P. M. Sutmuller, Rienk Offringa, Steven A. Rosenberg and Nicholas P. Restifo1

Surgery Branch, National Cancer Institute, NIH, Bethesda, Maryland 20892 [K. R. I., M. R. P., E. P. S., J. P. T., M. C., C. E. T., P. F. R., S. A. R., N. P. R.]; Therion Biologics Corporation, Cambridge, Massachusetts 02142 [A. G. Y., P. G.]; and Leiden University Medical Center, Leiden, The Netherlands, 2333 ZA [R. P. M. S., R. O.]

To study the induction of anti-"self" CD8+ T-cell reactivity against the tumor antigen gp100, we used a mouse transgenic for a chimeric HLA-A*0201/H-2 Kb molecule (A2/Kb). We immunized the mice with a recombinant vaccinia virus encoding a form of gp100 that had been modified at position 210 (from a threonine to a methionine) to increase epitope binding to the restricting class I molecule. Immunogens containing the "anchor-fixed" modification elicited anti-self CD8+ T cells specific for the wild-type gp100209–217 peptide pulsed onto target cells. More important, these cells specifically recognized the naturally presented epitope on the surface of an A2/Kb-expressing murine melanoma, B16. These data indicate that anchor-fixing epitopes could enhance the function of recombinant virus-based immunogens.




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