Polyclonal immune responses to antigens associated with cancer signaling pathways and new strategies to enhance cancer vaccines.
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.
Duke Comprehensive Cancer Center, Department of Surgery, Duke University Medical Center, 2424 Erwin Road, Suite 601, Durham, NC 27710, USA.
Timothy M
TM
Clay
Takuya
T
Osada
Zachary C
ZC
Hartman
Amy
A
Hobeika
Gayathri
G
Devi
Michael A
MA
Morse
H Kim
HK
Lyerly
D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D019496:Cancer Vaccines / Q000276:immunology*; D002986:Clinical Trials as Topic; D006801:Humans; D007167:Immunotherapy; D000077341:Lapatinib; D009369:Neoplasms / Q000188:drug therapy / Q000276:immunology* / Q000628:therapy; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000276:immunology; D011799:Quinazolines / Q000627:therapeutic use; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D000068878:Trastuzumab
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D019496:Cancer Vaccines; D000077341:Lapatinib; D011505:Protein-Tyrosine Kinases; D011799:Quinazolines; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C508053:ERBB2 protein, human