Abstract 2400: Treatment of colorectal cancer patients after resection of metastases with a tumor lysate pulsed dendritic cell vaccine: association between immune response and recurrence free survival

Abstract

Abstract Introduction. Phase III trials have shown that a vaccine consisting of irradiated autologous tumor cells plus bacille Calmette-Guerin (BCG) can induce anti-tumor immune responses in patients after resection of colorectal cancer. We have demonstrated in preclinical studies that an intranodally injected tumor lysate pulsed dendritic cell (DC) vaccine induces a more potent immune response than tumor cells plus BCG. Preclinical studies also indicate that DC maturation via signaling through CD40 increases vaccine potency. Patients and Methods. Twenty six patients who had undergone resection of colorectal metastases were treated with an intranodal injection of a vaccine consisting of autologous tumor lysate pulsed dendritic cells. Keyhole limpet hemocyanin (KLH) was added to the lysate as an adjuvant and a control protein. Patients were randomized to receive DCs that had been either activated or not activated with rhCD40L. Immune responses were evaluated with a dye dilution proliferation assay, an IFNγ ELISPOT assay and delayed type hypersensitivity (DTH) testing. All patients were followed for a minimum of 5.5 years after vaccination. Results. The vaccine was administered to all patients with minimal toxicity. Immunization induced an autologous tumor specific proliferative T cell immune response in 8 of 24 assessable patients (33%), a tumor specific IFNγ secretory response in 10 of 24 patients (42%) and a DTH response to autologous tumor cells in 14 of 23 patients (61%). KLH specific responses were induced in 54%, 83% and 60% of patients by proliferation, IFNγ ELISPOT and DTH assays, respectively. Use of this whole cell antigen source induced peptide (CEA, Her-2 neu, Muc-1) specific T cell immune responses in half of the assayed patients. Relapse free survival (RFS) was 58%, 41% and 37% at 1, 2 and 5 years. Patients with evidence of a vaccine induced anti-tumor proliferative T cell immune response one week after vaccination had a markedly better RFS at 5 years (67% vs 31%, p=0.057) than non-responders. There was a trend towards better RFS at 5 years (67% vs 23%, p= 0.09) in patients who developed a vaccine induced tumor specific IFNγ T cell response. No association was observed between induction of KLH specific immune responses and RFS. DCs grown in the presence of rhCD40L were observed to have a significantly greater expression of the costimulatory molecule CD86 and the maturation marker CD83. However, rhCD40L DC activation did not significantly affect the percentage of patients with positive immune responses. Conclusions. Adjuvant treatment of patients after resection of colorectal metastases with a tumor lysate pulsed dendritic cell vaccine induced tumor specific immune responses in a high proportion of patients. There was an association between induction of tumor specific immune responses and recurrence free survival. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2400.