Developing a Rational Tumor Vaccine Therapy for Renal Cell Carcinoma: Immune Yin and Yang

@article{citeulike:1570869, abstract = {In patients with progressive malignancy, the natural balance between proinflammatory (Yang) and inhibitory (regulatory or Yin) immune pathways is disrupted and favors cancer-specific immune suppression. Therapy with interleukin 2 (IL-2) can mobilize immune effector cells that recognize and destroy cancer. High-dose IL-2 is the only therapy that has consistently induced complete durable remissions in patients with metastatic renal cell carcinoma (RCC) but only in a few of them. The lack of benefit in most metastatic RCC patients is likely due to the ineffective manipulation of other immune circuits critical in regulating tumor cytotoxic pathways. The limited clinical activity of IL-2, RCC vaccines, and other immune therapies to date leads us to postulate that effective clinical treatment strategies will need to simultaneously enhance proinflammatory pathways and disrupt regulatory pathways. We present preliminary studies in RCC patients to highlight the complexity of the regulatory pathways and our approach to shifting the balance of proinflammatory and regulatory immune pathways using dendritic cell-tumor lysate vaccine followed by cytokine therapy. 10.1158/1078-0432.CCR-06-2064}, author = {Ernstoff, Marc S. and Crocenzi, Todd S. and Seigne, John D. and Crosby, Nancy A. and Cole, Bernard F. and Fisher, Jan L. and Uhlenhake, Jill C. and Mellinger, Diane and Foster, Cathy and Farnham, Conrad J. and Mackay, Kathleen and Szczepiorkowski, Zbigniew M. and Webber, Susan M. and Schned, Alan R. and Harris, Robert D. and Barth, Richard J. and Heaney, John A. and Noelle, Randolph J. }, citeulike-article-id = {1570869}, doi = {10.1158/1078-0432.CCR-06-2064}, journal = {Clin Cancer Res}, keywords = {randy-noelle}, month = {January}, number = {2}, pages = {733s--740}, posted-at = {2007-08-16 21:45:04}, priority = {2}, title = {Developing a Rational Tumor Vaccine Therapy for Renal Cell Carcinoma: Immune Yin and Yang}, url = {http://dx.doi.org/10.1158/1078-0432.CCR-06-2064}, volume = {13}, year = {2007} }

TY - JOUR ID - citeulike:1570869 L3 - citeulike-article-id:1570869 TI - Developing a Rational Tumor Vaccine Therapy for Renal Cell Carcinoma: Immune Yin and Yang JF - Clin Cancer Res VL - 13 IS - 2 SP - 733s EP - 740 N2 - In patients with progressive malignancy, the natural balance between proinflammatory (Yang) and inhibitory (regulatory or Yin) immune pathways is disrupted and favors cancer-specific immune suppression. Therapy with interleukin 2 (IL-2) can mobilize immune effector cells that recognize and destroy cancer. High-dose IL-2 is the only therapy that has consistently induced complete durable remissions in patients with metastatic renal cell carcinoma (RCC) but only in a few of them. The lack of benefit in most metastatic RCC patients is likely due to the ineffective manipulation of other immune circuits critical in regulating tumor cytotoxic pathways. The limited clinical activity of IL-2, RCC vaccines, and other immune therapies to date leads us to postulate that effective clinical treatment strategies will need to simultaneously enhance proinflammatory pathways and disrupt regulatory pathways. We present preliminary studies in RCC patients to highlight the complexity of the regulatory pathways and our approach to shifting the balance of proinflammatory and regulatory immune pathways using dendritic cell-tumor lysate vaccine followed by cytokine therapy. 10.1158/1078-0432.CCR-06-2064 KW - randy-noelle AU - Ernstoff, Marc AU - Crocenzi, Todd AU - Seigne, John AU - Crosby, Nancy AU - Cole, Bernard AU - Fisher, Jan AU - Uhlenhake, Jill AU - Mellinger, Diane AU - Foster, Cathy AU - Farnham, Conrad AU - Mackay, Kathleen AU - Szczepiorkowski, Zbigniew AU - Webber, Susan AU - Schned, Alan AU - Harris, Robert AU - Barth, Richard AU - Heaney, John AU - Noelle, Randolph PY - 2007/01/15/ UR - http://dx.doi.org/10.1158/1078-0432.CCR-06-2064 ER -