A randomized trial of ex vivo CD40L activation of a dendritic cell vaccine in colorectal cancer patients: tumor-specific immune responses are associated with improved survival.
OBJECTIVE
To determine whether an autologous dendritic cell (DC) vaccine could induce antitumor immune responses in patients after resection of colorectal cancer metastases and whether these responses could be enhanced by activating DCs with CD40L.


METHODS
Twenty-six patients who had undergone resection of colorectal metastases were treated with intranodal injections of an autologous tumor lysate- and control protein [keyhole limpet hemocyanin (KLH)]-pulsed DC vaccine. Patients were randomized to receive DCs that had been either activated or not activated with CD40L. All patients were followed for a minimum of 5.5 years.


RESULTS
Immunization induced an autologous tumor-specific T-cell proliferative or IFNγ enzyme-linked immunospot response in 15 of 24 assessable patients (63%) and a tumor-specific DTH response in 61%. Patients with evidence of a vaccine-induced, tumor-specific T-cell proliferative or IFNγ response 1 week after vaccination had a markedly better recurrence-free survival (RFS) at 5 years (63% versus 18%, P = 0.037) than nonresponders. In contrast, no association was observed between induction of KLH-specific immune responses and RFS. CD40L maturation induced CD86 and CD83 expression on DCs but had no effect on immune responses or RFS.


CONCLUSIONS
Adjuvant treatment of patients after resection of colorectal metastases with an autologous tumor lysate-pulsed, DC vaccine-induced, tumor-specific immune responses in a high proportion of patients. There was an association between induction of tumor-specific immune responses and RFS. Activation of this DC vaccine with CD40L did not lead to increased immune responses.
Barth
Richard J
RJ
Department of Surgery, Section of General Surgery, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire 03756, USA. Richard.J.Barth.Jr@Dartmouth.edu
Fisher
Dawn A
DA
Wallace
Paul K
PK
Channon
Jacqueline Y
JY
Noelle
Randolph J
RJ
Gui
Jiang
J
Ernstoff
Marc S
MS
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D023201:CD40 Ligand / Q000276:immunology*; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000276:immunology* / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000276:immunology* / Q000628:therapy*; D003713:Dendritic Cells / Q000276:immunology* / Q000637:transplantation*; D058501:Enzyme-Linked Immunospot Assay; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016019:Survival Analysis; D014182:Transplantation, Autologous; D016896:Treatment Outcome
D019496:Cancer Vaccines; D023201:CD40 Ligand