The article discusses the progress and challenges in cancer immunotherapy, particularly focusing on cancer vaccines. Despite significant advancements in understanding tumor-associated antigens and the development of various vaccine approaches, clinical responses have been limited. The authors highlight that the low objective response rate (2.6%) in their trials and similar rates in others suggest that current cancer vaccines may not be as effective as hoped. They attribute this to the reliance on surrogate endpoints and subjective criteria, such as histologic evidence of tumor necrosis or lymphocyte infiltration, rather than objective clinical tumor regression. The article also reviews the preclinical and clinical data from various cancer vaccine trials, including peptide vaccines, 'naked' DNA, dendritic cells, recombinant viruses, and adenoviruses. Despite the widespread use of these vaccines, the overall response rate remains low, indicating the need for new strategies. The authors emphasize the importance of generating and activating sufficient numbers of highly avid T cells capable of recognizing tumor antigens and infiltrating the tumor microenvironment. The article further discusses the limitations of current cancer vaccines, such as the inability to generate enough activated T cells and the lack of an inflammatory environment to activate these cells. It suggests that future research should focus on improving vaccine formulations, enhancing T cell activation, and creating conditions that promote T cell infiltration and activation at the tumor site. The authors also highlight the potential of adoptive transfer of antitumor T cells, which have shown promising results in both mouse models and human clinical trials, as a more effective approach to treating solid tumors. In conclusion, the article calls for a reevaluation of cancer immunotherapy trials, emphasizing the need for standardized criteria for evaluating clinical responses and increased efforts to develop more effective cancer vaccines.The article discusses the progress and challenges in cancer immunotherapy, particularly focusing on cancer vaccines. Despite significant advancements in understanding tumor-associated antigens and the development of various vaccine approaches, clinical responses have been limited. The authors highlight that the low objective response rate (2.6%) in their trials and similar rates in others suggest that current cancer vaccines may not be as effective as hoped. They attribute this to the reliance on surrogate endpoints and subjective criteria, such as histologic evidence of tumor necrosis or lymphocyte infiltration, rather than objective clinical tumor regression. The article also reviews the preclinical and clinical data from various cancer vaccine trials, including peptide vaccines, 'naked' DNA, dendritic cells, recombinant viruses, and adenoviruses. Despite the widespread use of these vaccines, the overall response rate remains low, indicating the need for new strategies. The authors emphasize the importance of generating and activating sufficient numbers of highly avid T cells capable of recognizing tumor antigens and infiltrating the tumor microenvironment. The article further discusses the limitations of current cancer vaccines, such as the inability to generate enough activated T cells and the lack of an inflammatory environment to activate these cells. It suggests that future research should focus on improving vaccine formulations, enhancing T cell activation, and creating conditions that promote T cell infiltration and activation at the tumor site. The authors also highlight the potential of adoptive transfer of antitumor T cells, which have shown promising results in both mouse models and human clinical trials, as a more effective approach to treating solid tumors. In conclusion, the article calls for a reevaluation of cancer immunotherapy trials, emphasizing the need for standardized criteria for evaluating clinical responses and increased efforts to develop more effective cancer vaccines.