Immunologic Research

, Volume 49, Issue 1–3, pp 235–247 | Cite as

Polyclonal immune responses to antigens associated with cancer signaling pathways and new strategies to enhance cancer vaccines

  • Timothy M. Clay
  • Takuya Osada
  • Zachary C. Hartman
  • Amy Hobeika
  • Gayathri Devi
  • Michael A. Morse
  • H. Kim LyerlyEmail author


Aberrant signaling pathways are a hallmark of cancer. A variety of strategies for inhibiting signaling pathways have been developed, but monoclonal antibodies against receptor tyrosine kinases have been among the most successful. A challenge for these therapies is therapeutic unresponsiveness and acquired resistance due to mutations in the receptors, upregulation of alternate growth and survival pathways, or inadequate function of the monoclonal antibodies. Vaccines are able to induce polyclonal responses that can have a multitude of affects against the target molecule. We began to explore therapeutic vaccine development to antigens associated with these signaling pathways. We provide an illustrative example in developing therapeutic cancer vaccines inducing polyclonal adaptive immune responses targeting the ErbB family member HER2. Further, we will discuss new strategies to augment the clinical efficacy of cancer vaccines by enhancing vaccine immunogenicity and reversing the immunosuppressive tumor microenvironment.


Cancer immunotherapy Polyclonal Vaccines Antigens Active immunotherapy 



This work was supported by grants from the National Cancer Institute [NCI P50 CA89496-01 and 5P50CA068438 to HKL, NCI R01 CA95447 to TMC]; Department of Defense Breast Cancer Research Program Clinical Translational Research Award [BC050221 to TMC]; and Susan G. Komen for the Cure Awards [HKL and Postdoctoral Fellowship Award KG080627 to ZCH].


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Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Timothy M. Clay
    • 1
    • 3
  • Takuya Osada
    • 1
  • Zachary C. Hartman
    • 1
  • Amy Hobeika
    • 1
  • Gayathri Devi
    • 1
  • Michael A. Morse
    • 2
  • H. Kim Lyerly
    • 1
    • 3
    Email author
  1. 1.Duke Comprehensive Cancer Center, Department of SurgeryDuke University Medical CenterDurhamUSA
  2. 2.Department of Medicine, Division of Medical OncologyDuke University Medical CenterDurhamUSA
  3. 3.Department of ImmunologyDuke University Medical CenterDurhamUSA

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