title: A randomized phase II study of immunization with dendritic cells modified with poxvectors encoding CEA and MUC1 compared with the same poxvectors plus GM-CSF for resected metastatic colorectal cancer.
abstract: OBJECTIVE
  To determine whether 1 of 2 vaccines based on dendritic cells (DCs) and poxvectors encoding CEA (carcinoembryonic antigen) and MUC1 (PANVAC) would lengthen survival in patients with resected metastases of colorectal cancer (CRC).
  
  
  BACKGROUND
  Recurrences after complete resections of metastatic CRC remain frequent. Immune responses to CRC are associated with fewer recurrences, suggesting a role for cancer vaccines as adjuvant therapy. Both DCs and poxvectors are potent stimulators of immune responses against cancer antigens.
  
  
  METHODS
  Patients, disease-free after CRC metastasectomy and perioperative chemotherapy (n = 74), were randomized to injections of autologous DCs modified with PANVAC (DC/PANVAC) or PANVAC with per injection GM-CSF (granulocyte-macrophage colony-stimulating factor). Endpoints were recurrence-free survival overall survival, and rate of CEA-specific immune responses. Clinical outcome was compared with that of an unvaccinated, contemporary group of patients who had undergone CRC metastasectomy, received similar perioperative therapy, and would have otherwise been eligible for the study.
  
  
  RESULTS
  Recurrence-free survival at 2 years was similar (47% and 55% for DC/PANVAC and PANVAC/GM-CSF, respectively) (χ P = 0.48). At a median follow-up of 35.7 months, there were 2 of 37 deaths in the DC/PANVAC arm and 5 of 37 deaths in the PANVAC/GM-CSF arm. The rate and magnitude of T-cell responses against CEA was statistically similar between study arms. As a group, vaccinated patients had superior survival compared with the contemporary unvaccinated group.
  
  
  CONCLUSIONS
  Both DC and poxvector vaccines have similar activity. Survival was longer for vaccinated patients than for a contemporary unvaccinated group, suggesting that a randomized trial of poxvector vaccinations compared with standard follow-up after metastasectomy is warranted. (NCT00103142).
authors: Departments of *Medicine, †Biostatistics and Bioinformatics, ‡Surgery, Duke University Medical Center §Duke Comprehensive Cancer Center, ‖Department of Immunology, Duke University Medical Center, Durham, NC ¶Georgetown University, Washington, DC **MD Anderson Cancer Center, Houston, TX ††Wake Forest University Baptist Medical Center, Winston-Salem, NC ‡‡Earle Chiles Cancer Center, Providence Portland Medical Center, Portland, OR §§Medical University of South Carolina, Charleston, SC ‖‖Moffitt Cancer Center, Tampa, FL. Dr Chang is now with Virginia Oncology Associates, Newport News, VA. Dr Clay is now with GlaxoSmithKline, Rixensart, Belgium.
authors: Michael A
authors: MA
authors: Morse
authors: Donna
authors: D
authors: Niedzwiecki
authors: John L
authors: JL
authors: Marshall
authors: Christopher
authors: C
authors: Garrett
authors: David Z
authors: DZ
authors: Chang
authors: Mebea
authors: M
authors: Aklilu
authors: Todd S
authors: TS
authors: Crocenzi
authors: David J
authors: DJ
authors: Cole
authors: Sophie
authors: S
authors: Dessureault
authors: Amy C
authors: AC
authors: Hobeika
authors: Takuya
authors: T
authors: Osada
authors: Mark
authors: M
authors: Onaitis
authors: Bryan M
authors: BM
authors: Clary
authors: David
authors: D
authors: Hsu
authors: Gayathri R
authors: GR
authors: Devi
authors: Anuradha
authors: A
authors: Bulusu
authors: Robert P
authors: RP
authors: Annechiarico
authors: Vijaya
authors: V
authors: Chadaram
authors: Timothy M
authors: TM
authors: Clay
authors: H Kim
authors: HK
authors: Lyerly
mesh_terms: D000328:Adult; D000368:Aged; D019496:Cancer Vaccines; D002272:Carcinoembryonic Antigen / Q000235:genetics; D015179:Colorectal Neoplasms / Q000473:pathology / Q000517:prevention & control* / Q000601:surgery; D003713:Dendritic Cells; D018572:Disease-Free Survival; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006801:Humans; D007114:Immunization / Q000379:methods*; D008297:Male; D008562:Membrane Glycoproteins; D008875:Middle Aged; D018396:Mucin-1 / Q000235:genetics; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local / Q000517:prevention & control*; D011212:Poxviridae / Q000235:genetics
chemical_list: D019496:Cancer Vaccines; D002272:Carcinoembryonic Antigen; C060192:MUC1 protein, human; D008562:Membrane Glycoproteins; D018396:Mucin-1; C518274:Panvac-VF; D016178:Granulocyte-Macrophage Colony-Stimulating Factor
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