In the past decade, significant progress has been made in tumor immunology, but clinical application of cancer vaccines remains limited due to reliance on surrogate endpoints rather than actual tumor regression. A study of 440 patients treated with various cancer vaccines showed an objective response rate of only 2.6%, comparable to other trials. The authors highlight the need for alternative strategies that can induce cancer regression in preclinical and clinical models. The molecular identification of tumor-associated antigens has spurred the development of new immunotherapies for solid cancers. However, cancer vaccines, which aim to treat growing tumors, have not consistently shown clinical success. Despite this, they remain popular due to their ease of administration and minimal side effects. The focus on cancer vaccines may be due to the success of viral vaccines in preventing diseases, but this does not translate to effective treatment of established tumors. The study analyzed 440 patients with metastatic cancer treated with 541 different vaccines. Most patients had melanoma, with 65% having visceral disease. The vaccines included peptides, dendritic cells, and viral vectors. The overall objective response rate was 2.6%, with only 14 patients showing clinical responses. These responses were mostly in patients with skin or lymph node disease, not visceral disease. The study also found that many vaccine trials use soft criteria that make it difficult to assess true tumor regression. This has led to overestimation of vaccine effectiveness. The authors emphasize the need for standardized clinical response criteria, such as RECIST, to evaluate vaccine efficacy accurately. The study also discusses the challenges of using cancer vaccines to treat solid tumors. Immune cells must infiltrate and activate within the tumor to cause regression, which is difficult in solid tumors. In contrast, lymphoid tumors are more responsive to dendritic cell vaccines because they allow easier access to the circulation and express costimulatory molecules. The study highlights the potential of cell transfer therapies, which have shown success in treating large, established tumors in mice. These therapies involve transferring activated antitumor T cells into lymphodepleted patients, leading to tumor regression. This approach has shown promise in human trials, with objective responses in 51% of patients. The study concludes that cancer vaccines have not been effective in causing tumor regression, but this does not mean they are ineffective. Instead, it highlights the need for improved vaccine strategies that can generate sufficient immune cells and activate them within the tumor. Future research should focus on enhancing adjuvants, improving antigen presentation, and reducing immune suppression to improve vaccine efficacy.In the past decade, significant progress has been made in tumor immunology, but clinical application of cancer vaccines remains limited due to reliance on surrogate endpoints rather than actual tumor regression. A study of 440 patients treated with various cancer vaccines showed an objective response rate of only 2.6%, comparable to other trials. The authors highlight the need for alternative strategies that can induce cancer regression in preclinical and clinical models. The molecular identification of tumor-associated antigens has spurred the development of new immunotherapies for solid cancers. However, cancer vaccines, which aim to treat growing tumors, have not consistently shown clinical success. Despite this, they remain popular due to their ease of administration and minimal side effects. The focus on cancer vaccines may be due to the success of viral vaccines in preventing diseases, but this does not translate to effective treatment of established tumors. The study analyzed 440 patients with metastatic cancer treated with 541 different vaccines. Most patients had melanoma, with 65% having visceral disease. The vaccines included peptides, dendritic cells, and viral vectors. The overall objective response rate was 2.6%, with only 14 patients showing clinical responses. These responses were mostly in patients with skin or lymph node disease, not visceral disease. The study also found that many vaccine trials use soft criteria that make it difficult to assess true tumor regression. This has led to overestimation of vaccine effectiveness. The authors emphasize the need for standardized clinical response criteria, such as RECIST, to evaluate vaccine efficacy accurately. The study also discusses the challenges of using cancer vaccines to treat solid tumors. Immune cells must infiltrate and activate within the tumor to cause regression, which is difficult in solid tumors. In contrast, lymphoid tumors are more responsive to dendritic cell vaccines because they allow easier access to the circulation and express costimulatory molecules. The study highlights the potential of cell transfer therapies, which have shown success in treating large, established tumors in mice. These therapies involve transferring activated antitumor T cells into lymphodepleted patients, leading to tumor regression. This approach has shown promise in human trials, with objective responses in 51% of patients. The study concludes that cancer vaccines have not been effective in causing tumor regression, but this does not mean they are ineffective. Instead, it highlights the need for improved vaccine strategies that can generate sufficient immune cells and activate them within the tumor. Future research should focus on enhancing adjuvants, improving antigen presentation, and reducing immune suppression to improve vaccine efficacy.