Present immunoprevention and immunotherapeutic approaches against cancer suffer from the limitation of being not "sterilizing" procedures, as very poor protection against the tumor is obtained. Thus newly conceived anti-tumor vaccination strategies are urgently needed. Here we will introduce the concept of Suitable Antigen Availability (SAA) as a key parameter to get optimal and protective adaptive immune response against tumor. Through the description of successful preventive or therapeutic experimental approaches to vaccinate the host against the tumor we will show that SAA can be achieved in various ways, particularly by rendering tumor cells MHC-II positive via transfection with the MHC-II transcriptional activator CIITA. Here SAA is generated by the function of tumor's newly expressed MHC-II molecules to present tumor-associated antigens to tumor-specific TH cells. In the second case, SAA is generated by treating established tumors with neovasculature-targeted TNFa. In conjuction with Melphalan, targeted TNFa delivery produces extensive areas of tumor necrosis that generate SAA capable of optimally activate tumorspecific TH cells which in turn are responsible of activating CTL immune effectors. Interestingly, the success in tumor eradication and/or growth arrest generated by classical therapies such as radiotherapy and chemotherapy in some instances can be re-interpreted on the basis of an adaptive immune response induced via SAA. Therefore, focussing on strategies to generate SAA may have an important impact on fighting and defeating cancer.
(C) 2013 Lippincott Williams & Wilkins, Inc.