Treatment of Ovarian Carcinoma
Ovarian cancer, like most solid tumors, is in dire need of effective therapies. The significance of this therapy lies in its promise to spearhead the development of combination immunotherapy and to introduce novel approaches to therapeutic immunomodulation.
Active Immunotherapy using therapeutic cancer vaccines have the potential to break immune tolerance and induce long-term immune response against cancer cells. DCs loaded with whole tumor lysate have been investigated in several clinical trials for their ability to induce anti-tumor T-cell responses. Beneficial anti-tumor responses have been observed in some patients, illustrating the potential of this approach. DCs can be classified into different subsets, depending on their lineage and receptor expression pattern. Their distinct biology can be exploited for different therapeutic strategies. The most widely used DCs in clinical trials to date are myeloid DCs differentiated from peripheral blood monocytes. In most trials, “classic” DCs are fully differentiated over seven days in the presence of recombinant granulocyte-macrophage colony stimulating factor (GM-CSF) and interleukin 4 (IL-4). These DCs exhibit high phagocytic and antigen-processing capability. Upon maturation with an appropriate stimulus, Day-7 DCs up regulate costimulatory surface molecules such as CD80, CD86, CD40, and lymph node-homing receptors such as CCR7, and can efficiently prime naïve T-cells.
A meta-analysis of 173 published peer-reviewed immunotherapy trials found that 8.1% of patients vaccinated with whole tumor antigen (n=1,733) experienced objective clinical responses, compared with 3.6% of patients vaccinated with defined tumor antigens.