Tuesday, November 30, 2010

Tumor for Tumor

A new paper appeared in Clinical Cancer Research on fighting tumor with Tumor derived vaccines from dendrite cells. Dendritic cells are critical to the human body's immune system, helping identify targets, or antigens, and then stimulating the immune system to react against those antigens. The new research grew dendritic cells from a sample of a patient's blood, mixed them with proteins from the patient's tumor, and then injected the mixture into the patient as a vaccine. The vaccine then stimulated an anti-tumor response from T-cells, a kind of white blood cell that protects the body from disease.
Purpose: 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.
Experimental Design: 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.
Conclusion: 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. Clin Cancer Res; 16(22); 5548–56. ©2010 AACR.
Citation: Richard J. Barth, Jr., Dawn A. Fisher, Paul K. Wallace, Jacqueline Y. Channon, Randolph J. Noelle, Jiang Gui, and Marc S. Ernstoff, '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', Clin Cancer Res November 15, 2010 doi:10.1158/1078-0432.CCR-10-2138

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