Editing Cancer vaccine (section)

== Hypothesized problems ==
A vaccine against a particular virus is relatively easy to create. The virus is foreign to the body, and therefore expresses [[antigen]]s that the [[immune system]] can recognize. Furthermore, viruses usually only provide a few viable variants. By contrast, developing vaccines for viruses that mutate constantly such as [[influenza]] or [[HIV]] has been problematic. A tumor can have many cell types of cells, each with different cell-surface antigens. Those cells are derived from each patient and display few if any antigens that are foreign to that individual. This makes it difficult for the immune system to distinguish cancer cells from normal cells. Some scientists believe that [[renal cancer]] and [[melanoma]] are the two cancers with most evidence of spontaneous and effective immune responses, possibly because they often display antigens that are evaluated as foreign. Many attempts at developing cancer vaccines are directed against these tumors. However, Provenge's success in prostate cancer, a disease that never spontaneously regresses, suggests that cancers other than melanoma and renal cancer may be equally amenable to immune attack.{{citation needed|date=June 2020}}

However, most vaccine clinical trials have failed or had modest results according to the standard [[RECIST]] criteria.<ref>{{cite journal | vauthors = Rosenberg SA, Yang JC, Restifo NP | title = Cancer immunotherapy: moving beyond current vaccines | journal = Nature Medicine | volume = 10 | issue = 9 | pages = 909–915 | date = September 2004 | pmid = 15340416 | pmc = 1435696 | doi = 10.1038/nm1100 }}</ref> The precise reasons are unknown, but possible explanations include:
* Disease stage too advanced: bulky tumor deposits actively suppress the immune system using mechanisms such as secretion of [[cytokines]] that inhibit immune activity. The most suitable stage for a cancer vaccine is likely to be early, when the tumor volume is low, which complicates the trial process, which take upwards of five years and require many patients to reach measurable end points. One alternative is to target patients with residual disease after surgery, radiotherapy or chemotherapy that does not harm the immune system.
* Escape loss variants (that target a single [[tumor antigen]]) are likely to be less effective. Tumors are heterogeneous and antigen expression differs markedly between tumors (even in the same patient). The most effective vaccine is likely to raise an immune response against a broad range of tumor antigens to minimise the chance of the tumor mutating and becoming resistant to the therapy.
* Prior treatments may have modified tumors in ways that nullify the vaccine. (Numerous clinical trials treated patients following chemotherapy that may destroy the immune system. Patients who are immune suppressed are not good candidates for vaccines.)
* Some tumors progress rapidly and/or unpredictably, and they can outpace the immune system. Developing a mature immune response to a vaccine may require months, but some cancers (e.g. advanced pancreatic) can kill patients in less time.
* Many cancer vaccine clinical trials target patients' immune responses. Correlations typically show that the patients with the strongest immune responses lived the longest, offering evidence that the vaccine is working. An alternative explanation is that patients with the best immune responses were healthier patients with a better prognosis, and would have survived longest even without the vaccine.