Breast Cancer Research and Treatment

, Volume 106, Issue 3, pp 371–382 | Cite as

VRP immunotherapy targeting neu: treatment efficacy and evidence for immunoediting in a stringent rat mammary tumor model

  • Amanda K. Laust
  • Brandon W. Sur
  • Kehui Wang
  • Bolyn Hubby
  • Jonathan F. Smith
  • Edward L. Nelson
Preclinical Study


The ability to overcome intrinsic tolerance to a strict “self” tumor-associated antigen (TAA) and successfully treat pre-existing tumor is the most stringent test for anti-tumor immunotherapeutic strategies. Although this capacity has been demonstrated in various models using complicated strategies that may not be readily translated into the clinical arena, straightforward antigen-specific immunotherapeutic strategies in the most stringent models of common epithelial cancers have largely failed to meet this standard. We employed an immunotherapeutic strategy using an alphavirus-based, virus-like replicon particle (VRP), which has in vivo tropism for dendritic cells, to elicit immune responses to the non-mutated TAA rat neu in an aggressive rat mammary tumor model. Using this VRP-based immunotherapeutic strategy targeting a single TAA, we generated effective anti-tumor immunity in the setting of pre-existing tumor resulting in the cure of 36% of rats over multiple experiments, P = 0.002. We also observed down-regulation of rat neu expression in tumors that showed initial responses followed by tumor escape with resumption of rapid tumor growth. These responses were accompanied by significant anti-tumor proliferative responses and CD8+ cellular tumor infiltrates, all of which were restricted to animals receiving the anti-neu immunotherapy. Together these data, obtained in a stringent “self” TAA model, indicate that the VRP-based antigen-specific immunotherapy elicits sufficiently potent immune responses to exert immunologic pressure, selection, and editing of the growing tumors, thus supporting the activity of this straightforward immunotherapy and suggesting that it is a promising platform upon which to build even more potent strategies.


Breast cancer Immunoediting Immunoselection Immunotherapy neu Venezuelan Equine Encephalitis replicon VRP 



Support for this work was provided by The Susan G. Komen Foundation (BCTR0100619) and by the Chao Family Comprehensive Cancer Center at the University of California, Irvine. The authors also wish to acknowledge the assistance and support of Tatiana Krasieva, PhD and Bruce Tromberg, PhD of the Beckman Laser Institute at the University of California, Irvine in the performance of fluorescence microscopy.


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Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Amanda K. Laust
    • 2
    • 3
  • Brandon W. Sur
    • 1
  • Kehui Wang
    • 1
  • Bolyn Hubby
    • 4
  • Jonathan F. Smith
    • 4
  • Edward L. Nelson
    • 1
    • 2
    • 3
  1. 1.Department of Medicine, Division of Hematology/Oncology, School of MedicineUniversity of CaliforniaIrvineUSA
  2. 2.Department of Molecular Biology and Biochemistry, School of Biological SciencesUniversity of CaliforniaIrvineUSA
  3. 3.Center for ImmunologyUniversity of CaliforniaIrvineUSA
  4. 4.AlphaVax, Inc.Research Triangle ParkUSA

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